A. D. Sperber, D. Dumitrascu, and S. Fukudo, The global prevalence of IBS in adults remains elusive due to the heterogeneity of studies: a Rome Foundation working team literature review, Gut, 2016.

S. Buhner, Q. Li, and S. Vignali, Activation of human enteric neurons by supernatants of colonic biopsy specimens from patients with irritable bowel syndrome, Gastroenterology, vol.137, pp.1425-1459, 2009.

N. Cenac, T. Bautzova, L. Faouder, and P. , Quantification and potential functions of endogenous agonists of transient receptor potential channels in patients with irritable bowel syndrome, Gastroenterology, vol.149, pp.433-477, 2015.

E. E. Valdez-morales, J. Overington, and R. Guerrero-alba, Sensitization of peripheral sensory nerves by mediators from colonic biopsies of diarrhea-predominant irritable bowel syndrome patients: a role for PAR2, Am J Gastroenterol, vol.108, pp.1634-1677, 2013.

E. Hyun, P. Andrade-gordon, and M. Steinhoff, Protease-activated receptor-2 activation: a major actor in intestinal inflammation, Gut, vol.57, pp.1222-1231, 2008.

N. Moussaoui, M. Larauche, and M. Biraud, Limited nesting stress alters maternal behavior and in vivo intestinal permeability in male wistar pup rats, PLoS ONE, vol.11, p.155037, 2016.

M. Larauche, A. Mulak, and Y. S. Kim, Visceral analgesia induced by acute and repeated water avoidance stress in rats: sex difference in opioid involvement, Neurogastroenterol Motil, vol.24, pp.1031-547, 2012.

M. Larauche, G. Gourcerol, and L. Wang, Cortagine, a CRF1 agonist, induces stress-like alterations of colonic function and visceral hypersensitivity in rodents primarily through peripheral pathways, Am J Physiol Gastrointest Liver Physiol, vol.297, pp.215-242, 2009.

N. Cenac, C. Altier, and J. P. Motta, Potentiation of TRPV4 signalling by histamine and serotonin: an important mechanism for visceral hypersensitivity, Gut, vol.59, pp.481-489, 2010.

C. Cirillo, G. Sarnelli, and F. Turco, Proinflammatory stimuli activates human-derived enteroglial cells and induces autocrine nitric oxide production, Neurogastroenterol Motil, vol.23, pp.372-82, 2011.

D. Grundmann, M. Klotz, and H. Rabe, Isolation of high-purity myenteric plexus from adult human and mouse gastrointestinal tract, Sci Rep, vol.5, p.9226, 2015.

G. Sarnelli, P. Vanden-berghe, and P. Raeymaekers, Inhibitory effects of galanin on evoked [Ca2+]i responses in cultured myenteric neurons, Am J Physiol Gastrointest Liver Physiol, vol.286, pp.1009-1023, 2004.

K. Oikonomopoulou, K. K. Hansen, and M. Saifeddine, Proteinase-mediated cell signalling: targeting proteinase-activated receptors (PARs) by kallikreins and more, Biol Chem, vol.387, pp.677-85, 2006.
URL : https://hal.archives-ouvertes.fr/hal-00320920

R. Ramachandran, F. Noorbakhsh, and K. Defea, Targeting proteinase-activated receptors: therapeutic potential and challenges, Nat Rev Drug Discov, vol.11, pp.69-86, 2012.

A. C. Chin, W. Y. Lee, and A. Nusrat, Neutrophil-mediated activation of epithelial protease-activated receptors-1 and-2 regulates barrier function and transepithelial migration, J Immunol, vol.181, pp.5702-5712, 2008.

J. P. Motta, L. G. Bermudez-humaran, and C. Deraison, Food-grade bacteria expressing elafin protect against inflammation and restore colon homeostasis, Sci Transl Med, vol.4, pp.158-202, 2012.
URL : https://hal.archives-ouvertes.fr/hal-01204261

K. J. Livak and T. D. Schmittgen, Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method, Methods, vol.25, pp.402-410, 2001.

E. Hyun, R. Ramachandran, and N. Cenac, Insulin modulates protease-activated receptor 2 signaling: implications for the innate immune response, J Immunol, vol.184, pp.2702-2711, 2010.

C. Rolland-fourcade, Gut, vol.0, pp.1-12, 2017.

D. Tooth, K. Garsed, and G. Singh, Characterisation of faecal protease activity in irritable bowel syndrome with diarrhoea: origin and effect of gut transit, Gut, vol.63, pp.753-60, 2014.

A. P. Kerckhoffs, T. Linde, J. J. Akkermans, and L. M. , Trypsinogen IV, serotonin transporter transcript levels and serotonin content are increased in small intestine of irritable bowel syndrome patients, Neurogastroenterol Motil, vol.20, pp.900-907, 2008.

A. P. Alloy, O. Kayode, and R. Wang, Mesotrypsin has evolved four unique residues to cleave trypsin inhibitors as substrates, J Biol Chem, vol.290, pp.21523-21558, 2015.

D. Pendlebury, R. Wang, and R. D. Henin, Sequence and conformational specificity in substrate recognition: several human Kunitz protease inhibitor domains are specific substrates of mesotrypsin, J Biol Chem, vol.289, pp.32783-97, 2014.

W. Knecht, G. S. Cottrell, and S. Amadesi, Trypsin IV or mesotrypsin and p23 cleave protease-activated receptors 1 and 2 to induce inflammation and hyperalgesia, J Biol Chem, vol.282, pp.26089-100, 2007.

C. Ibeakanma, F. Ochoa-cortes, and M. Miranda-morales, Brain-gut interactions increase peripheral nociceptive signaling in mice with postinfectious irritable bowel syndrome, Gastroenterology, vol.141, pp.2098-108, 2011.

K. Mueller, K. Michel, and D. Krueger, Activity of protease-activated receptors in the human submucous plexus, Gastroenterology, vol.141, pp.2088-97, 2011.

N. Vergnolle, Clinical relevance of proteinase activated receptors ( pars) in the gut, Gut, vol.54, pp.867-74, 2005.

C. Rolland-fourcade, Gut, vol.0, pp.1-12, 2017.

, Elafine protège de la colite. Plus largement, en posant la question du mécanisme d'action de L'Elafine, 2017.

K. Baranger, M. Zani, J. Chandenier, S. Dallet-choisy, and T. Moreau, The antibacterial and antifungal properties of trappin-2 (pre-elafin) do not depend on its protease inhibitory function, FEBS J, vol.275, 2008.

A. Bellemare, N. Vernoux, S. Morin, S. M. Gagné, and Y. Bourbonnais, Structural and antimicrobial properties of human pre-elafin/trappin-2 and derived peptides against Pseudomonas aeruginosa, BMC Microbiol, vol.10, p.253, 2010.

L. G. Bermúdez-humarán, J. Motta, C. Aubry, P. Kharrat, L. Rous-martin et al., Serine protease inhibitors protect better than IL-10 and TGF-? anti-inflammatory cytokines against mouse colitis when delivered by recombinant lactococci, Microb. Cell Factories, vol.14, p.26, 2015.

R. Boxio, J. Wartelle, B. Nawrocki-raby, B. Lagrange, L. Malleret et al., Neutrophil elastase cleaves epithelial cadherin in acutely injured lung epithelium, Respir. Res, vol.17, p.129, 2016.
URL : https://hal.archives-ouvertes.fr/inserm-01382904

D. Bustos, G. Negri, J. A. De-paula, M. Di-carlo, V. Yapur et al., Colonic proteinases: increased activity in patients with ulcerative colitis, Medicina (Mex.), vol.58, pp.262-264, 1998.

M. W. Butler, I. Robertson, C. M. Greene, S. J. O'neill, C. C. Taggart et al., Elafin prevents lipopolysaccharide-induced AP-1 and NF-kappaB activation via an effect on the ubiquitin-proteasome pathway, J. Biol. Chem, vol.281, pp.34730-34735, 2006.

A. C. Chin, N. Vergnolle, W. K. Macnaughton, J. L. Wallace, M. D. Hollenberg et al., Proteinase-activated receptor 1 activation induces epithelial apoptosis and increases intestinal permeability, Proc. Natl. Acad. Sci. U. S. A, vol.100, pp.11104-11109, 2003.

A. C. Chin, W. Y. Lee, A. Nusrat, N. Vergnolle, P. et al., Neutrophilmediated activation of epithelial protease-activated receptors-1 and-2 regulates barrier function and transepithelial migration, J. Immunol. Baltim. Md, vol.181, pp.5702-5710, 1950.

M. Dabek, L. Ferrier, R. Roka, K. Gecse, A. Annahazi et al., Luminal cathepsin g and protease-activated receptor 4: a duet involved in alterations of the colonic epithelial barrier in ulcerative colitis, Am. J. Pathol, vol.175, pp.207-214, 2009.

A. G. Drannik, K. Nag, X. Yao, B. M. Henrick, T. B. Ball et al., Anti-HIV-1 activity of elafin depends on its nuclear localization and altered innate immune activation in female genital epithelial cells, PloS One, vol.7, 2012.

M. Galliano, E. Toulza, N. Jonca, S. L. Gonias, G. Serre et al., Binding of ?2ML1 to the Low Density Lipoprotein Receptor-Related Protein 1 (LRP1) Reveals a New Role for LRP1 in the Human Epidermis, PLoS ONE, vol.3, 2008.

S. Hosomi, A. Kaser, and R. S. Blumberg, Role of endoplasmic reticulum stress and autophagy as interlinking pathways in the pathogenesis of inflammatory bowel disease, Curr. Opin. Gastroenterol, vol.31, pp.81-88, 2015.

A. Kaser, S. Zeissig, and R. S. Blumberg, Inflammatory bowel disease, Annu. Rev. Immunol, vol.28, pp.573-621, 2010.

K. Luo and S. S. Cao, Endoplasmic Reticulum Stress in Intestinal Epithelial Cell Function and Inflammatory Bowel Disease, Gastroenterol. Res. Pract, 2015.

H. Maekawa and D. M. Tollefsen, Role of the Proposed Serpin-Enzyme Complex Receptor Recognition Site in Binding and Internalization of Thrombin-Heparin Cofactor II Complexes by Hepatocytes, J. Biol. Chem, vol.271, pp.18604-18609, 1996.

J. Motta, L. G. Bermúdez-humarán, C. Deraison, L. Martin, C. Rolland et al., Food-grade bacteria expressing elafin protect against inflammation and restore colon homeostasis, Sci. Transl, 2012.
URL : https://hal.archives-ouvertes.fr/hal-01204261

R. Panaccione, J. G. Ferraz, B. , and P. , Advances in medical therapy of inflammatory bowel disease, Curr. Opin. Pharmacol, vol.5, pp.566-572, 2005.

D. H. Perlmutter, G. I. Glover, M. Rivetna, C. S. Schasteen, F. et al., Identification of a serpin-enzyme complex receptor on human hepatoma cells and human monocytes, Proc. Natl. Acad. Sci. U. S. A, vol.87, p.3753, 1990.

J. M. Sallenave, Antimicrobial activity of antiproteinases, Biochem. Soc. Trans, vol.30, pp.111-115, 2002.

J. Sallenave, Secretory leukocyte protease inhibitor and elafin/trappin-2: versatile mucosal antimicrobials and regulators of immunity, Am. J. Respir. Cell Mol. Biol, vol.42, pp.635-643, 2010.

D. K. Strickland, S. C. Muratoglu, A. , and T. M. , Serpin-Enzyme Receptors: LDL Receptor-Related Protein 1, Methods Enzymol, vol.499, p.17, 2011.

C. C. Taggart, S. Cryan, S. Weldon, A. Gibbons, C. M. Greene et al., Secretory leucoprotease inhibitor binds to NF-kappaB binding sites in monocytes and inhibits p65 binding, J. Exp. Med, vol.202, pp.1659-1668, 2005.

E. Vachon, Y. Bourbonnais, C. D. Bingle, S. J. Rowe, M. F. Janelle et al., Anti-inflammatory effect of pre-elafin in lipopolysaccharide-induced acute lung inflammation, Biol. Chem, vol.383, pp.1249-1256, 2002.

R. M. Vejborg, V. Hancock, A. M. Petersen, K. A. Krogfelt, and P. Klemm, , 2011.

, Comparative genomics of Escherichia coli isolated from patients with inflammatory bowel disease, BMC Genomics, vol.12, p.316

N. Vergnolle, Protease-activated receptors as drug targets in inflammation and pain, Pharmacol. Ther, vol.123, pp.292-309, 2009.

N. Vergnolle, Protease inhibition as new therapeutic strategy for GI diseases, Gut, 2016.

T. Verrier, B. Solhonne, J. Sallenave, and I. Garcia-verdugo, The WAP protein Trappin-2/Elafin: a handyman in the regulation of inflammatory and immune responses, Int. J. Biochem. Cell Biol, vol.44, pp.1377-1380, 2012.

E. Wine, J. C. Ossa, S. D. Gray-owen, and P. M. Sherman, Adherent-invasive Escherichia coli, strain LF82 disrupts apical junctional complexes in polarized epithelia, BMC Microbiol, vol.9, p.180, 2009.

Q. L. Ying and S. R. Simon, Kinetics of the inhibition of proteinase 3 by elafin, Am. J. Respir. Cell Mol. Biol, vol.24, pp.83-89, 2001.

A. P. Yu, L. A. Cabanilla, E. Q. Wu, P. M. Mulani, and J. Chao, The costs of Crohn's disease in the United States and other Western countries: a systematic review, Curr. Med. Res. Opin, vol.24, pp.319-328, 2008.

P. Zhao, T. Lieu, N. Barlow, S. Sostegni, S. Haerteis et al., Neutrophil Elastase Activates Protease-activated Receptor-2 (PAR2) and Transient Receptor Potential Vanilloid 4 (TRPV4) to Cause Inflammation and Pain, ANNEXE Publication scientifique : Epithelial expression and function of trypsin-3 in irritable bowel syndrome, vol.290, pp.13875-13887, 2015.

C. Fourcade, A. Denadai-souza, C. Cirillo, C. Lopez, J. O. Jaramillo et al., , 2017.

. Brevet,

, Method of treatment of gut disease such as irritable bowel syndrome (IBS), Ep N° 16, vol.306, p.760

A. Núria-solà-tapias, C. Denadai-souza, C. Rolland-fourcade, A. Blanpied, C. Edir et al., Ulcerative colitis-associated endoplasmic reticulum stress induces trypsin activity affecting innate immune response, International Congress of Mucosal Immunology (ICMI) ?, 2017.

C. Rolland-fourcade, A. Denadai-souza, C. Cirillo, J. P. Motta, T. Bautzova et al., L'épithélium intestinal est source de l'activité trypsine, 2016.

C. Rolland-fourcade, A. Denadai-souza, J. P. Motta, T. Bautzova, N. Cenac et al., Epithelial trypsin signals to sensory neurons : release in Irritable Bowel Syndrome, 2015.

C. Rolland-fourcade, A. Denadai-souza, J. P. Motta, T. Bautzova, N. Cenac et al., Epithelial mesotrypsin in IBS : expression and function, 2015.

M. N. Adams, R. Ramachandran, M. Yau, J. Y. Suen, D. P. Fairlie et al., Structure, function and pathophysiology of protease activated receptors, Pharmacol. Ther, vol.130, pp.248-282, 2011.

J. Aerssens, K. Hillsley, P. J. Peeters, R. De-hoogt, A. Stanisz et al., Alterations in the brain-gut axis underlying visceral chemosensitivity in Nippostrongylus brasiliensis-infected mice, Gastroenterology, vol.132, pp.1375-1387, 2007.

A. Akbar, J. R. Walters, G. , and S. , Review article: visceral hypersensitivity in irritable bowel syndrome: molecular mechanisms and therapeutic agents, Aliment. Pharmacol. Ther, vol.30, pp.423-435, 2009.

E. D. Al-chaer, M. Kawasaki, and P. J. Pasricha, A new model of chronic visceral hypersensitivity in adult rats induced by colon irritation during postnatal development, Gastroenterology, vol.119, pp.1276-1285, 2000.

T. A. Almeida, J. Rojo, P. M. Nieto, F. M. Pinto, M. Hernandez et al., Tachykinins and tachykinin receptors: structure and activity relationships, Curr. Med. Chem, vol.11, pp.2045-2081, 2004.

S. Amadesi, J. Nie, N. Vergnolle, G. S. Cottrell, E. F. Grady et al., Protease-activated receptor 2 sensitizes the capsaicin receptor transient receptor potential vanilloid receptor 1 to induce hyperalgesia, J. Neurosci. Off. J. Soc. Neurosci, vol.24, pp.4300-4312, 2004.

S. Amasheh, N. Meiri, A. H. Gitter, T. Schöneberg, J. Mankertz et al., Claudin-2 expression induces cation-selective channels in tight junctions of epithelial cells, J. Cell Sci, vol.115, pp.4969-4976, 2002.

R. E. Andersson, G. Olaison, C. Tysk, and A. Ekbom, Appendectomy is followed by increased risk of Crohn's disease, Gastroenterology, vol.124, pp.40-46, 2003.

A. Andoh, T. Tsujikawa, and Y. Fujiyama, Role of dietary fiber and short-chain fatty acids in the colon, Curr. Pharm. Des, vol.9, pp.347-358, 2003.

A. Andoh, Y. Deguchi, O. Inatomi, Y. Yagi, S. Bamba et al., Immunohistochemical study of chymase-positive mast cells in inflammatory bowel disease, Oncol. Rep, vol.16, pp.103-107, 2006.

A. Andoh, H. Imaeda, T. Aomatsu, O. Inatomi, S. Bamba et al., Comparison of the fecal microbiota profiles between ulcerative colitis and Crohn's disease using terminal restriction fragment length polymorphism analysis, J. Gastroenterol, vol.46, pp.479-486, 2011.

A. Annaházi, K. Gecse, M. Dabek, A. Ait-belgnaoui, A. Rosztóczy et al., Fecal proteases from diarrheic-IBS and ulcerative colitis patients exert opposite effect on visceral sensitivity in mice, Pain, vol.144, pp.209-217, 2009.

F. Annunziato, L. Cosmi, V. Santarlasci, L. Maggi, F. Liotta et al., Phenotypic and functional features of human Th17 cells, J. Exp. Med, vol.204, pp.1849-1861, 2007.

A. V. Apkarian, M. C. Bushnell, R. Treede, and J. Zubieta, Human brain mechanisms of pain perception and regulation in health and disease, Eur. J. Pain Lond. Engl, vol.9, pp.463-484, 2005.

N. Arpaia, C. Campbell, X. Fan, S. Dikiy, J. Van-der-veeken et al., Metabolites produced by commensal bacteria promote peripheral regulatory T-cell generation, Nature, vol.504, pp.451-455, 2013.

S. Asfaha, V. Brussee, K. Chapman, D. W. Zochodne, and N. Vergnolle, , 2002.

, Proteinase-activated receptor-1 agonists attenuate nociception in response to noxious stimuli, Br. J. Pharmacol, vol.135, pp.1101-1106

C. Auffray, D. K. Fogg, E. Narni-mancinelli, B. Senechal, C. Trouillet et al., CX3CR1+ CD115+ CD135+ common macrophage/DC precursors and the role of CX3CR1 in their response to inflammation, J. Exp. Med, vol.206, pp.595-606, 2009.
URL : https://hal.archives-ouvertes.fr/pasteur-00428989

C. Augé, D. Balz-hara, M. Steinhoff, N. Vergnolle, C. et al., Proteaseactivated receptor-4 (PAR 4): a role as inhibitor of visceral pain and hypersensitivity, Neurogastroenterol. Motil. Off. J. Eur. Gastrointest. Motil. Soc, vol.21, pp.1189-107, 2009.

S. Auvin, F. Molinié, C. Gower-rousseau, F. Brazier, V. Merle et al., Incidence, clinical presentation and location at diagnosis of pediatric inflammatory bowel disease: a prospective population-based study in northern France (1988-1999), J. Pediatr. Gastroenterol. Nutr, vol.41, pp.49-55, 2005.

L. G. Axelsson, E. Landström, T. J. Goldschmidt, A. Grönberg, and A. C. Bylund-fellenius, Dextran sulfate sodium (DSS) induced experimental colitis in immunodeficient mice: effects in CD4(+)-cell depleted, athymic and NK-cell depleted SCID mice, Inflamm. Res. Off. J. Eur. Histamine Res. Soc. Al, vol.45, pp.181-191, 1996.

F. Bäckhed, R. E. Ley, J. L. Sonnenburg, D. A. Peterson, G. et al., Hostbacterial mutualism in the human intestine, Science, vol.307, pp.1915-1920, 2005.

J. Bae, Y. Kim, M. Park, R. , and A. R. , Concentration dependent dual effect of thrombin in endothelial cells via Par-1 and Pi3 Kinase, J. Cell. Physiol, vol.219, pp.744-751, 2009.

J. Bae, I. Kim, R. , and A. R. , Thrombin down-regulates the TGF-betamediated synthesis of collagen and fibronectin by human proximal tubule epithelial cells through the EPCR-dependent activation of PAR-1, J. Cell. Physiol, vol.225, pp.233-239, 2010.

M. Banasaz, E. Norin, R. Holma, and T. Midtvedt, Increased enterocyte production in gnotobiotic rats mono-associated with Lactobacillus rhamnosus GG, Appl. Environ. Microbiol, vol.68, pp.3031-3034, 2002.

J. Banchereau and R. M. Steinman, Dendritic cells and the control of immunity, Nature, vol.392, pp.245-252, 1998.

U. Bank, B. Küpper, D. Reinhold, T. Hoffmann, A. et al., Evidence for a crucial role of neutrophil-derived serine proteases in the inactivation of interleukin-6 at sites of inflammation, FEBS Lett, vol.461, pp.235-240, 1999.

K. Baranger, M. Zani, J. Chandenier, S. Dallet-choisy, and T. Moreau, The antibacterial and antifungal properties of trappin-2 (pre-elafin) do not depend on its protease inhibitory function, FEBS J, vol.275, 2008.

G. Barbara, R. De-giorgio, Y. Deng, B. Vallance, P. Blennerhassett et al., Role of immunologic factors and cyclooxygenase 2 in persistent postinfective enteric muscle dysfunction in mice, Gastroenterology, vol.120, pp.1729-1736, 2001.

G. Barbara, V. Stanghellini, R. De-giorgio, C. Cremon, G. S. Cottrell et al., Activated mast cells in proximity to colonic nerves correlate with abdominal pain in irritable bowel syndrome, Gastroenterology, vol.126, pp.693-702, 2004.

G. Barbara, B. Wang, V. Stanghellini, R. De-giorgio, C. Cremon et al., Mast Cell-Dependent Excitation of Visceral-Nociceptive Sensory Neurons in Irritable Bowel Syndrome, Gastroenterology, vol.132, pp.26-37, 2007.

G. Barbara, C. Cremon, R. D. Giorgio, G. Dothel, L. Zecchi et al., Mechanisms Underlying Visceral Hypersensitivity in Irritable Bowel Syndrome, vol.13, pp.308-315, 2011.

N. Barker, J. H. Van-es, J. Kuipers, P. Kujala, M. Van-den-born et al., Identification of stem cells in small intestine and colon by marker gene Lgr5, Nature, vol.449, pp.1003-1007, 2007.

H. E. Barksby, S. R. Lea, P. M. Preshaw, T. , and J. J. , The expanding family of interleukin-1 cytokines and their role in destructive inflammatory disorders, Clin. Exp. Immunol, vol.149, pp.217-225, 2007.

M. Barman, D. Unold, K. Shifley, E. Amir, K. Hung et al., , 2008.

, Enteric salmonellosis disrupts the microbial ecology of the murine gastrointestinal tract, Infect. Immun, vol.76, pp.907-915

P. J. Barnes, Anti-inflammatory actions of glucocorticoids: molecular mechanisms, Clin. Sci. Lond. Engl, vol.94, pp.557-572, 1979.

J. C. Barrett, S. Hansoul, D. L. Nicolae, J. H. Cho, R. H. Duerr et al., Genome-wide association defines more than 30 distinct susceptibility loci for Crohn's disease, Nat. Genet, vol.40, pp.955-962, 2008.

A. I. Basbaum, D. M. Bautista, G. Scherrer, J. , and D. , Cellular and Molecular Mechanisms of Pain, Cell, vol.139, pp.267-284, 2009.

M. Bashashati, N. Rezaei, A. Shafieyoun, D. P. Mckernan, L. Chang et al., Cytokine imbalance in irritable bowel syndrome: a systematic review and meta-analysis, Neurogastroenterol. Motil. Off. J. Eur. Gastrointest. Motil. Soc, vol.26, pp.1036-1048, 2014.

M. Bashashati, N. Rezaei, A. Shafieyoun, D. P. Mckernan, L. Chang et al., Cytokine imbalance in irritable bowel syndrome: a systematic review and meta-analysis, Neurogastroenterol. Motil, vol.26, pp.1036-1048, 2014.

D. C. Baumgart, C. , and S. R. , Inflammatory bowel disease: cause and immunobiology, The Lancet, vol.369, pp.1627-1640, 2007.

D. M. Bautista, S. Jordt, T. Nikai, P. R. Tsuruda, A. J. Read et al., TRPA1 mediates the inflammatory actions of environmental irritants and proalgesic agents, Cell, vol.124, pp.1269-1282, 2006.

J. K. Beatty, A. Bhargava, and A. G. Buret, Post-infectious irritable bowel syndrome: mechanistic insights into chronic disturbances following enteric infection, World J. Gastroenterol, vol.20, pp.3976-3985, 2014.

K. Becker, C. Niederau, and T. Frieling, Fecal excretion of alpha 2macroglobulin: a novel marker for disease activity in patients with inflammatory bowel disease, Z. Gastroenterol, vol.37, pp.597-605, 1999.

A. Belaaouaj, R. Mccarthy, M. Baumann, Z. Gao, T. J. Ley et al., Mice lacking neutrophil elastase reveal impaired host defense against gram negative bacterial sepsis, Nat. Med, vol.4, pp.615-618, 1998.

A. Bellemare, N. Vernoux, S. Morin, S. M. Gagné, and Y. Bourbonnais, Structural and antimicrobial properties of human pre-elafin/trappin-2 and derived peptides against Pseudomonas aeruginosa, BMC Microbiol, vol.10, p.253, 2010.

E. I. Benchimol, K. J. Fortinsky, P. Gozdyra, M. Van-den-heuvel, J. Van-limbergen et al., Epidemiology of pediatric inflammatory bowel disease: a systematic review of international trends, Inflamm. Bowel Dis, vol.17, pp.423-439, 2011.

S. Ben-horin, U. Kopylov, C. , and Y. , Optimizing anti-TNF treatments in inflammatory bowel disease, Autoimmun. Rev, vol.13, pp.24-30, 2014.

L. G. Bermúdez-humarán, J. Motta, C. Aubry, P. Kharrat, L. Rous-martin et al., Serine protease inhibitors protect better than IL-10 and TGF-? anti-inflammatory cytokines against mouse colitis when delivered by recombinant lactococci, Microb. Cell Factories, vol.14, p.26, 2015.

C. N. Bernstein, Treatment of IBD: Where We Are and Where We Are Going, Am. J. Gastroenterol, 2014.

C. N. Bernstein, A. Wajda, L. W. Svenson, A. Mackenzie, M. Koehoorn et al., The epidemiology of inflammatory bowel disease in Canada: a population-based study, Am. J. Gastroenterol, vol.101, pp.1559-1568, 2006.

N. Bertiaux-vandaële, S. B. Youmba, L. Belmonte, S. Lecleire, M. Antonietti et al., The Expression and the Cellular Distribution of the Tight Junction Proteins Are Altered in Irritable Bowel Syndrome Patients With Differences According to the Disease Subtype, Am. J. Gastroenterol, vol.106, pp.2165-2173, 2011.

C. L. Bevins and N. H. Salzman, Paneth cells, antimicrobial peptides and maintenance of intestinal homeostasis, Nat. Rev. Microbiol, vol.9, pp.356-368, 2011.

C. Bezençon, J. Le-coutre, and S. Damak, Taste-signaling proteins are coexpressed in solitary intestinal epithelial cells, Chem. Senses, vol.32, pp.41-49, 2007.

K. Bielefeldt, N. Ozaki, and G. F. Gebhart, Experimental ulcers alter voltagesensitive sodium currents in rat gastric sensory neurons, Gastroenterology, vol.122, pp.394-405, 2002.

K. Bielefeldt, B. Davis, and D. G. Binion, Pain and inflammatory bowel disease, Inflamm. Bowel Dis, vol.15, pp.778-788, 2009.

J. R. Biesiekierski, E. D. Newnham, P. M. Irving, J. S. Barrett, M. Haines et al., Gluten causes gastrointestinal symptoms in subjects without celiac disease: a double-blind randomized placebocontrolled trial, Am. J. Gastroenterol, vol.106, pp.508-514, 2011.

M. Bjerknes and H. Cheng, Modulation of specific intestinal epithelial progenitors by enteric neurons, Proc. Natl. Acad. Sci, vol.98, pp.12497-12502, 2001.

B. D. Blackhart, K. Emilsson, D. Nguyen, W. Teng, A. J. Martelli et al., Ligand cross-reactivity within the protease-activated receptor family, J. Biol. Chem, vol.271, pp.16466-16471, 1996.

L. A. Blackshaw, S. J. Brookes, D. Grundy, and M. Schemann, Sensory transmission in the gastrointestinal tract, Neurogastroenterol. Motil. Off. J. Eur. Gastrointest. Motil. Soc, vol.19, pp.1-19, 2007.

S. A. Blair, S. V. Kane, D. R. Clayburgh, and J. R. Turner, Epithelial myosin light chain kinase expression and activity are upregulated in inflammatory bowel disease, Lab. Investig. J. Tech. Methods Pathol, vol.86, pp.191-201, 2006.

D. V. Bohórquez, R. A. Shahid, A. Erdmann, A. M. Kreger, Y. Wang et al., Neuroepithelial circuit formed by innervation of sensory enteroendocrine cells, J. Clin. Invest, vol.125, pp.782-786, 2015.

D. Boltin, T. T. Perets, A. Vilkin, and Y. Niv, Mucin function in inflammatory bowel disease: an update, J. Clin. Gastroenterol, vol.47, pp.106-111, 2013.

G. Bonizzi, K. , and M. , The two NF-?B activation pathways and their role in innate and adaptive immunity, Trends Immunol, vol.25, pp.280-288, 2004.

C. Bonnart, C. Deraison, M. Lacroix, and A. Hovnanian, , 2010.

, Med. Sci. MS, vol.26, pp.681-685

C. A. Borgoño, I. P. Michael, and E. P. Diamandis, Human tissue kallikreins: physiologic roles and applications in cancer, Mol. Cancer Res. MCR, vol.2, pp.257-280, 2004.

J. I. Borissoff, S. Heeneman, E. Kilinç, P. Kassák, R. Van-oerle et al., Early atherosclerosis exhibits an enhanced procoagulant state, Circulation, vol.122, pp.821-830, 2010.

N. Borregaard, M. Sehested, B. S. Nielsen, H. Sengeløv, and L. Kjeldsen, , 1995.

, Biosynthesis of granule proteins in normal human bone marrow cells, Blood, vol.85, pp.812-817

C. Bourriaud, R. J. Robins, L. Martin, F. Kozlowski, E. Tenailleau et al., Lactate is mainly fermented to butyrate by human intestinal microfloras but inter-individual variation is evident, J. Appl. Microbiol, vol.99, pp.201-212, 2005.

R. Boxio, J. Wartelle, B. Nawrocki-raby, B. Lagrange, L. Malleret et al., Neutrophil elastase cleaves epithelial cadherin in acutely injured lung epithelium, Respir. Res, vol.17, p.129, 2016.
URL : https://hal.archives-ouvertes.fr/inserm-01382904

S. Bradesi, I. Schwetz, H. S. Ennes, C. M. Lamy, G. Ohning et al., Repeated exposure to water avoidance stress in rats: a new model for sustained visceral hyperalgesia, Am. J. Physiol.-Gastrointest. Liver Physiol, vol.289, pp.42-53, 2005.

S. Bradesi, I. Schwetz, H. S. Ennes, C. M. Lamy, G. Ohning et al., Repeated exposure to water avoidance stress in rats: a new model for sustained visceral hyperalgesia, Am. J. Physiol. Gastrointest. Liver Physiol, vol.289, pp.42-53, 2005.

J. M. Braz, M. A. Nassar, J. N. Wood, and A. I. Basbaum, Parallel "pain" pathways arise from subpopulations of primary afferent nociceptor, Neuron, vol.47, pp.787-793, 2005.

A. Brehmer, Structure of enteric neurons, Adv. Anat. Embryol. Cell Biol, vol.186, pp.1-91, 2006.

K. A. Brogden, Antimicrobial peptides: pore formers or metabolic inhibitors in bacteria?, Nat. Rev. Microbiol, vol.3, pp.238-250, 2005.

S. J. Brookes, N. J. Spencer, M. Costa, and V. P. Zagorodnyuk, Extrinsic primary afferent signalling in the gut, Nat. Rev. Gastroenterol. Hepatol, vol.10, pp.286-296, 2013.

M. Bruewer, M. Utech, A. I. Ivanov, A. M. Hopkins, C. A. Parkos et al., , 2005.

, Interferon-gamma induces internalization of epithelial tight junction proteins via a macropinocytosis-like process, FASEB J. Off. Publ. Fed. Am. Soc. Exp. Biol, vol.19, pp.923-933

S. Buonocore, P. P. Ahern, H. H. Uhlig, I. I. Ivanov, D. R. Littman et al., Innate lymphoid cells drive interleukin-23-dependent innate intestinal pathology, Nature, vol.464, pp.1371-1375, 2010.

D. Bustos, G. Negri, J. A. De-paula, M. Di-carlo, V. Yapur et al., Colonic proteinases: increased activity in patients with ulcerative colitis, Medicina (Mex.), vol.58, pp.262-264, 1998.

M. W. Butler, I. Robertson, C. M. Greene, S. J. O'neill, C. C. Taggart et al., Elafin prevents lipopolysaccharide-induced AP-1 and NF-kappaB activation via an effect on the ubiquitin-proteasome pathway, J. Biol. Chem, vol.281, pp.34730-34735, 2006.

M. S. Buzza, S. Netzel-arnett, T. Shea-donohue, A. Zhao, C. Lin et al., Membrane-anchored serine protease matriptase regulates epithelial barrier formation and permeability in the intestine, Proc. Natl. Acad. Sci. U. S. A, vol.107, pp.4200-4205, 2010.

M. Z. Cader and A. Kaser, Recent advances in inflammatory bowel disease: mucosal immune cells in intestinal inflammation, Gut, vol.62, pp.1653-1664, 2013.

C. T. Capaldo, D. N. Powell, K. , and D. , Layered defense: how mucus and tight junctions seal the intestinal barrier, J. Mol. Med. Berl. Ger, 2017.

A. Caputo, R. S. Garner, U. Winkler, D. Hudig, and R. C. Bleackley, Activation of recombinant murine cytotoxic cell proteinase-1 requires deletion of an amino-terminal dipeptide, J. Biol. Chem, vol.268, pp.17672-17675, 1993.

E. Cario, G. Gerken, and D. K. Podolsky, Toll-like receptor 2 controls mucosal inflammation by regulating epithelial barrier function, Gastroenterology, vol.132, pp.1359-1374, 2007.

M. J. Carter, A. J. Lobo, T. , and S. P. , Guidelines for the management of inflammatory bowel disease in adults, Gut, vol.53, pp.1-16, 2004.

B. D. Cash, M. S. Epstein, and S. M. Shah, A Novel Delivery System of Peppermint Oil Is an Effective Therapy for Irritable Bowel Syndrome Symptoms, Dig. Dis. Sci, vol.61, p.560, 2016.

G. H. Caughey, Mast cell tryptases and chymases in inflammation and host defense, Immunol. Rev, vol.217, pp.141-154, 2007.

N. Cenac, A. Coelho, C. Nguyen, S. Compton, P. Andrade-gordon et al., Induction of Intestinal Inflammation in Mouse by Activation of Proteinase-Activated Receptor-2, Am. J. Pathol, vol.161, 1903.
URL : https://hal.archives-ouvertes.fr/hal-01562307

N. Cenac, A. C. Chin, R. Garcia-villar, C. Salvador-cartier, L. Ferrier et al., PAR2 activation alters colonic paracellular permeability in mice via IFN-?-dependent and-independent pathways, J. Physiol, vol.558, pp.913-925, 2004.

N. Cenac, C. N. Andrews, M. Holzhausen, K. Chapman, G. Cottrell et al., Role for protease activity in visceral pain in irritable bowel syndrome, J. Clin. Invest, vol.117, pp.636-647, 2007.

L. Chang, S. Sundaresh, J. Elliott, P. A. Anton, P. Baldi et al., Dysregulation of the hypothalamic-pituitaryadrenal (HPA) axis in irritable bowel syndrome, Neurogastroenterol. Motil. Off. J. Eur. Gastrointest. Motil. Soc, vol.21, pp.149-159, 2009.

M. V. Chao, Neurotrophins and their receptors: a convergence point for many signalling pathways, Nat. Rev. Neurosci, vol.4, pp.299-309, 2003.

E. Chatzaki, P. D. Crowe, L. Wang, M. Million, Y. Taché et al., CRF receptor type 1 and 2 expression and anatomical distribution in the rat colon, J. Neurochem, vol.90, pp.309-316, 2004.

H. Chen, L. Duan, Y. Zhu, S. Ye, Y. Yang et al., , 2004.

, Beijing Da Xue Xue Bao, vol.36, pp.198-201

H. Cheng and C. P. Leblond, Origin, differentiation and renewal of the four main epithelial cell types in the mouse small intestine. V. Unitarian Theory of the origin of the four epithelial cell types, Am. J. Anat, vol.141, pp.537-561, 1974.

M. Cherrier, , 2014.

, Med. Sci. MS, vol.30, pp.280-288

W. D. Chey, A. J. Lembo, B. J. Lavins, S. J. Shiff, C. B. Kurtz et al., Linaclotide for Irritable Bowel Syndrome With Constipation: A 26-Week, Randomized, Double-blind, Placebo-Controlled Trial to Evaluate Efficacy and Safety, Am. J. Gastroenterol, vol.107, pp.1702-1712, 2012.

A. C. Chin, N. Vergnolle, W. K. Macnaughton, J. L. Wallace, M. D. Hollenberg et al., Proteinase-activated receptor 1 activation induces epithelial apoptosis and increases intestinal permeability, Proc. Natl. Acad. Sci. U. S. A, vol.100, pp.11104-11109, 2003.

A. C. Chin, N. Vergnolle, W. K. Macnaughton, J. L. Wallace, M. D. Hollenberg et al., Proteinase-activated receptor 1 activation induces epithelial apoptosis and increases intestinal permeability, Proc. Natl. Acad. Sci. U. S. A, vol.100, pp.11104-11109, 2003.

A. C. Chin, W. Y. Lee, A. Nusrat, N. Vergnolle, P. et al., Neutrophilmediated activation of epithelial protease-activated receptors-1 and-2 regulates barrier function and transepithelial migration, J. Immunol. Baltim. Md, vol.181, pp.5702-5710, 1950.

V. T. Chu, A. Beller, S. Rausch, J. Strandmark, M. Zänker et al., Eosinophils promote generation and maintenance of immunoglobulinA-expressing plasma cells and contribute to gut immune homeostasis, Immunity, vol.40, pp.582-593, 2014.

H. Chung, S. J. Pamp, J. A. Hill, N. K. Surana, S. M. Edelman et al., Gut immune maturation depends on colonization with a host-specific microbiota, Cell, vol.149, pp.1578-1593, 2012.

J. F. Cicmanec and I. A. Holder, Growth of Pseudomonas aeruginosa in normal and burned skin extract: role of extracellular proteases, Infect. Immun, vol.25, pp.477-483, 1979.

G. Clarke, E. M. Quigley, J. F. Cryan, and T. G. Dinan, Irritable bowel syndrome: towards biomarker identification, Trends Mol. Med, vol.15, pp.478-489, 2009.

P. Clavé, M. Acalovschi, J. K. Triantafillidis, Y. P. Uspensky, C. Kalayci et al., Randomised clinical trial: otilonium bromide improves frequency of abdominal pain, severity of distention and time to relapse in patients with irritable bowel syndrome, Aliment. Pharmacol. Ther, vol.34, pp.432-442, 2011.

N. Clerc and J. B. Furness, Intrinsic primary afferent neurones of the digestive tract, Neurogastroenterol. Motil. Off. J. Eur. Gastrointest. Motil. Soc, vol.16, issue.1, pp.24-27, 2004.

M. Coëffier, R. Gloro, N. Boukhettala, M. Aziz, S. Lecleire et al., Increased Proteasome-Mediated Degradation of Occludin in Irritable Bowel Syndrome, Am. J. Gastroenterol, vol.105, pp.1181-1188, 2010.

C. Coeshott, C. Ohnemus, A. Pilyavskaya, S. Ross, M. Wieczorek et al., Converting enzyme-independent release of tumor necrosis factor alpha and IL-1beta from a stimulated human monocytic cell line in the presence of activated neutrophils or purified proteinase 3, Proc. Natl. Acad. Sci. U. S. A, vol.96, pp.6261-6266, 1999.

A. J. Connolly, H. Ishihara, M. L. Kahn, R. V. Farese, and S. R. Coughlin, Role of the thrombin receptor in development and evidence for a second receptor, Nature, vol.381, pp.516-519, 1996.

H. J. Cooke, Y. Z. Wang, R. , and R. , Coordination of Cl-secretion and contraction by a histamine H2-receptor agonist in guinea pig distal colon, Am. J. Physiol, vol.265, pp.973-978, 1993.

J. L. Coombes, K. R. Siddiqui, C. V. Arancibia-cárcamo, J. Hall, C. Sun et al., A functionally specialized population of mucosal CD103+ DCs induces Foxp3+ regulatory T cells via a TGF-beta and retinoic acid-dependent mechanism, J. Exp. Med, vol.204, pp.1757-1764, 2007.

A. P. Corfield, D. Carroll, N. Myerscough, and C. S. Probert, Mucins in the gastrointestinal tract in health and disease, Front. Biosci. J. Virtual Libr, vol.6, pp.1321-1357, 2001.

J. Cosnes, Tobacco and IBD: relevance in the understanding of disease mechanisms and clinical practice, Best Pract. Res. Clin. Gastroenterol, vol.18, pp.481-496, 2004.

J. Cosnes, C. Gower-rousseau, P. Seksik, C. , and A. , Epidemiology and Natural History of Inflammatory Bowel Diseases, Gastroenterology, vol.140, pp.1785-1794, 2011.
URL : https://hal.archives-ouvertes.fr/hal-00631553

J. Cosnes, A. Bourrier, D. Laharie, S. Nahon, Y. Bouhnik et al., Early administration of azathioprine vs conventional management of Crohn's Disease: a randomized controlled trial, Gastroenterology, vol.145, pp.758-765, 2013.

E. Coss-adame and S. S. Rao, Brain and Gut Interactions in Irritable Bowel Syndrome: New Paradigms and New Understandings, vol.16, pp.1-8, 2014.

J. J. Cox, F. Reimann, A. K. Nicholas, G. Thornton, E. Roberts et al., An SCN9A channelopathy causes congenital inability to experience pain, Nature, vol.444, pp.894-898, 2006.

F. Creed, L. Fernandes, E. Guthrie, S. Palmer, J. Ratcliffe et al., The costeffectiveness of psychotherapy and paroxetine for severe irritable bowel syndrome, Gastroenterology, vol.124, pp.303-317, 2003.

C. Cremon, L. Gargano, A. M. Morselli-labate, D. Santini, R. F. Cogliandro et al., Mucosal Immune Activation in Irritable Bowel Syndrome: Gender-Dependence and Association With Digestive Symptoms, Am. J. Gastroenterol, vol.104, pp.392-400, 2009.

L. L. Cribbs, T-type Ca2+ channels in vascular smooth muscle: multiple functions, Cell Calcium, vol.40, pp.221-230, 2006.

L. Crouzet, E. Gaultier, C. Del'homme, C. Cartier, E. Delmas et al., The hypersensitivity to colonic distension of IBS patients can be transferred to rats through their fecal microbiota, Neurogastroenterol. Motil, vol.25, pp.272-282, 2013.

M. D. Crowell, Role of serotonin in the pathophysiology of the irritable bowel syndrome, Br. J. Pharmacol, vol.141, pp.1285-1293, 2004.

E. Csernok, M. Ai, W. L. Gross, D. Wicklein, A. Petersen et al., Wegener autoantigen induces maturation of dendritic cells and licenses them for Th1 priming via the protease-activated receptor-2 pathway, Blood, vol.107, pp.4440-4448, 2006.

M. Dabek, L. Ferrier, R. Roka, K. Gecse, A. Annahazi et al., Luminal cathepsin g and protease-activated receptor 4: a duet involved in alterations of the colonic epithelial barrier in ulcerative colitis, Am. J. Pathol, vol.175, pp.207-214, 2009.

D. 'alessio, F. R. Tsushima, K. Aggarwal, N. R. West, E. E. Willett et al., CD4+CD25+Foxp3+ Tregs resolve experimental lung injury in mice and are present in humans with acute lung injury, J. Clin. Invest, vol.119, pp.2898-2913, 2009.

J. Dalli, L. V. Norling, D. Renshaw, D. Cooper, K. Leung et al., , 2008.

, Annexin 1 mediates the rapid anti-inflammatory effects of neutrophil-derived microparticles, Blood, vol.112, pp.2512-2519

C. J. Damman, S. I. Miller, C. M. Surawicz, and T. L. Zisman, The microbiome and inflammatory bowel disease: is there a therapeutic role for fecal microbiota transplantation?, Am. J. Gastroenterol, vol.107, pp.1452-1459, 2012.

S. Danese, G. Fiorino, L. Peyrin-biroulet, E. Lucenteforte, G. Virgili et al., Biological agents for moderately to severely active ulcerative colitis: a systematic review and network meta-analysis, Ann. Intern. Med, vol.160, pp.704-711, 2014.

A. Darfeuille-michaud, J. Boudeau, P. Bulois, C. Neut, A. Glasser et al., High prevalence of adherent-invasive Escherichia coli associated with ileal mucosa in Crohn's disease, Gastroenterology, vol.127, pp.412-421, 2004.

D. Darmoul and A. J. Ouellette, Positional specificity of defensin gene expression reveals Paneth cell heterogeneity in mouse small intestine, Am. J. Physiol, vol.271, pp.68-74, 1996.

D. Palma, G. Lynch, M. D. Lu, J. Dang, V. T. Deng et al., Transplantation of fecal microbiota from patients with irritable bowel syndrome alters gut function and behavior in recipient mice, Sci. Transl. Med, vol.9, 2017.

J. J. Deberry, K. Bielefeldt, B. M. Davis, E. M. Szigethy, D. J. Hartman et al., Abdominal pain and the neurotrophic system in ulcerative colitis, Inflamm. Bowel Dis, vol.20, pp.2330-2339, 2014.

M. Delvaux, P. Denis, A. , and H. , Sexual abuse is more frequently reported by IBS patients than by patients with organic digestive diseases or controls. Results of a multicentre inquiry. French Club of Digestive Motility, Eur. J. Gastroenterol. Hepatol, vol.9, pp.345-352, 1997.

J. M. Devaney, C. M. Greene, C. C. Taggart, T. P. Carroll, S. J. O'neill et al., Neutrophil elastase up-regulates interleukin-8 via toll-like receptor 4, FEBS Lett, vol.544, pp.129-132, 2003.

M. Devani, M. Vecchi, S. Ferrero, E. C. Avesani, C. Arizzi et al., Kallikrein-kinin system in inflammatory bowel diseases: Intestinal involvement and correlation with the degree of tissue inflammation, Dig. Liver Dis. Off. J. Ital. Soc. Gastroenterol. Ital. Assoc. Study Liver, vol.37, pp.665-673, 2005.

S. J. Van-deventer, Review article: Chemokine production by intestinal epithelial cells: a therapeutic target in inflammatory bowel disease?, Aliment. Pharmacol. Ther, p.11, 1997.

H. B. Devlin, D. Datta, and A. W. Dellipiani, The incidence and prevalence of inflammatory bowel disease in North Tees Health District, World J. Surg, vol.4, pp.183-193, 1980.

T. Didari, S. Mozaffari, S. Nikfar, and M. Abdollahi, Effectiveness of probiotics in irritable bowel syndrome: Updated systematic review with meta-analysis, World J. Gastroenterol. WJG, vol.21, p.3072, 2015.

T. G. Dinan, E. M. Quigley, S. M. Ahmed, P. Scully, S. O'brien et al., Hypothalamic-Pituitary-Gut Axis Dysregulation in Irritable Bowel Syndrome: Plasma Cytokines as a Potential Biomarker, vol.130, pp.304-311, 2006.

T. G. Dinan, G. Clarke, E. M. Quigley, L. V. Scott, F. Shanahan et al., Enhanced cholinergic-mediated increase in the proinflammatory cytokine IL-6 in irritable bowel syndrome: role of muscarinic receptors, Am. J. Gastroenterol, vol.103, pp.2570-2576, 2008.

E. Distrutti, S. Cipriani, A. Mencarelli, B. Renga, and S. Fiorucci, Probiotics VSL#3 protect against development of visceral pain in murine model of irritable bowel syndrome, PloS One, vol.8, p.63893, 2013.

G. J. Dockray, Luminal sensing in the gut: an overview, J. Physiol. Pharmacol. Off. J. Pol. Physiol. Soc, vol.54, pp.9-17, 2003.

K. T. Dolan, C. , and E. B. , Diet, gut microbes, and the pathogenesis of inflammatory bowel diseases, Mol. Nutr. Food Res, p.61, 2017.

A. G. Drannik, K. Nag, X. Yao, B. M. Henrick, T. B. Ball et al., Anti-HIV-1 activity of elafin depends on its nuclear localization and altered innate immune activation in female genital epithelial cells, PloS One, vol.7, 2012.

D. A. Drossman, The functional gastrointestinal disorders and the Rome III process, Gastroenterology, vol.130, pp.1377-1390, 2006.

D. A. Drossman, W. D. Chey, J. F. Johanson, R. Fass, C. Scott et al., Clinical trial: lubiprostone in patients with constipation-associated irritable bowel syndrome-results of two randomized, placebo-controlled studies, Aliment. Pharmacol. Ther, vol.29, pp.329-341, 2009.

A. E. Dubin, P. , and A. , Nociceptors: the sensors of the pain pathway, J. Clin. Invest, vol.120, pp.3760-3772, 2010.

R. N. Dubois, S. B. Abramson, L. Crofford, R. A. Gupta, L. S. Simon et al., Cyclooxygenase in biology and disease, FASEB J. Off. Publ. Fed. Am. Soc. Exp. Biol, vol.12, pp.1063-1073, 1998.

L. Dubuquoy, E. A. Jansson, S. Deeb, S. Rakotobe, M. Karoui et al., Impaired expression of peroxisome proliferator-activated receptor gamma in ulcerative colitis, Gastroenterology, vol.124, pp.1265-1276, 2003.

S. Dulon, C. Candé, N. W. Bunnett, M. D. Hollenberg, M. Chignard et al., , 2003.

, Proteinase-Activated Receptor-2 and Human Lung Epithelial Cells, Am. J. Respir. Cell Mol. Biol, vol.28, pp.339-346

S. P. Dunlop, J. Hebden, E. Campbell, J. Naesdal, L. Olbe et al., Abnormal intestinal permeability in subgroups of diarrhea-predominant irritable bowel syndromes, Am. J. Gastroenterol, vol.101, pp.1288-1294, 2006.

P. S. Efskind, T. Bernklev, and M. H. Vatn, A Double-Blind Placebo-Controlled Trial with Loperamide in Irritable Bowel Syndrome, Scand. J. Gastroenterol, vol.31, pp.463-468, 1996.

L. J. Egan and W. J. Sandborn, Methotrexate for inflammatory bowel disease: pharmacology and preliminary results, Mayo Clin. Proc, vol.71, pp.69-80, 1996.

B. Egger, M. Bajaj-elliott, T. T. Macdonald, R. Inglin, V. E. Eysselein et al., Characterisation of acute murine dextran sodium sulphate colitis: cytokine profile and dose dependency, Digestion, vol.62, pp.240-248, 2000.

A. N. Elzouki, S. Eriksson, R. Löfberg, L. Nässberger, J. Wieslander et al., The prevalence and clinical significance of alpha 1-antitrypsin deficiency (PiZ) and ANCA specificities (proteinase 3, BPI) in patients with ulcerative colitis, Inflamm. Bowel Dis, vol.5, pp.246-252, 1999.

P. Enck, Q. Aziz, G. Barbara, A. D. Farmer, S. Fukudo et al., Irritable bowel syndrome, Nat. Rev. Dis. Primer, vol.2, p.16014, 2016.

S. Eswaran, A. Goel, and W. D. Chey, What role does wheat play in the symptoms of irritable bowel syndrome?, Gastroenterol. Hepatol, vol.9, pp.85-91, 2013.

V. A. Fadok, D. L. Bratton, A. Konowal, P. W. Freed, J. Y. Westcott et al., Macrophages that have ingested apoptotic cells in vitro inhibit proinflammatory cytokine production through autocrine/paracrine mechanisms involving TGF-beta, PGE2, and PAF, J. Clin. Invest, vol.101, pp.890-898, 1998.

M. Fang, K. J. Kovács, L. L. Fisher, and A. A. Larson, Thrombin inhibits NMDAmediated nociceptive activity in the mouse: possible mediation by endothelin, J. Physiol, vol.549, pp.903-917, 2003.

A. D. Farmer, A. , and Q. , Gut pain & visceral hypersensitivity, Br. J. Pain, vol.7, p.39, 2013.

B. G. Feagan, J. W. Mcdonald, J. Rochon, A. Laupacis, R. N. Fedorak et al., Low-dose cyclosporine for the treatment of Crohn's disease. The Canadian Crohn's Relapse Prevention Trial Investigators, N. Engl. J. Med, vol.330, pp.1846-1851, 1994.

B. G. Feagan, J. Rochon, R. N. Fedorak, E. J. Irvine, G. Wild et al., Methotrexate for the treatment of Crohn's disease. The North American Crohn's Study Group Investigators, N. Engl. J. Med, vol.332, pp.292-297, 1995.

D. T. Fearon and R. M. Locksley, The instructive role of innate immunity in the acquired immune response, Science, vol.272, pp.50-53, 1996.

C. Feistritzer, R. , and M. , Endothelial barrier protection by activated protein C through PAR1-dependent sphingosine 1-phosphate receptor-1 crossactivation, Blood, vol.105, pp.3178-3184, 2005.

A. Fichera and F. Michelassi, Surgical treatment of Crohn's disease, J. Gastrointest. Surg. Off. J. Soc. Surg. Aliment. Tract, vol.11, pp.791-803, 2007.

S. Fiorucci, A. Mencarelli, B. Palazzetti, E. Distrutti, N. Vergnolle et al., Proteinase-activated receptor 2 is an antiinflammatory signal for colonic lamina propria lymphocytes in a mouse model of colitis, Proc. Natl. Acad. Sci. U. S. A, vol.98, pp.13936-13941, 2001.

E. W. Fish, D. Shahrokh, R. Bagot, C. Caldji, T. Bredy et al., , 2004.

, Epigenetic Programming of Stress Responses through Variations in Maternal Care, Ann. N. Y. Acad. Sci, vol.1036, pp.167-180

W. M. Flanagan, B. Corthésy, R. J. Bram, and G. R. Crabtree, Nuclear association of a T-cell transcription factor blocked by FK-506 and cyclosporin A, Nature, vol.352, pp.803-807, 1991.

H. J. Flint, K. P. Scott, S. H. Duncan, P. Louis, and E. Forano, Microbial degradation of complex carbohydrates in the gut, Gut Microbes, vol.3, pp.289-306, 2012.

A. N. Flynn and A. G. Buret, Proteinase-activated receptor 1 (PAR-1) and cell apoptosis, Apoptosis Int. J. Program. Cell Death, vol.9, pp.729-737, 2004.

B. Foligne, R. Dessein, M. Marceau, S. Poiret, M. Chamaillard et al., Prevention and treatment of colitis with Lactococcus lactis secreting the immunomodulatory Yersinia LcrV protein, Gastroenterology, vol.133, pp.862-874, 2007.

A. C. Ford, J. Achkar, K. J. Khan, S. V. Kane, N. J. Talley et al., Efficacy of 5-aminosalicylates in ulcerative colitis: systematic review and metaanalysis, Am. J. Gastroenterol, vol.106, pp.601-616, 2011.

S. Fox, A. E. Leitch, R. Duffin, C. Haslett, and A. G. Rossi, Neutrophil apoptosis: relevance to the innate immune response and inflammatory disease, J. Innate Immun, vol.2, pp.216-227, 2010.

L. Franchi, N. Kamada, Y. Nakamura, A. Burberry, P. Kuffa et al., NLRC4-driven production of IL-1? discriminates between pathogenic and commensal bacteria and promotes host intestinal defense, Nat. Immunol, vol.13, pp.449-456, 2012.

D. Franchimont, S. Vermeire, H. El-housni, M. Pierik, K. Van-steen et al., Deficient host-bacteria interactions in inflammatory bowel disease? The toll-like receptor, 2004.

, Asp299gly polymorphism is associated with Crohn's disease and ulcerative colitis, Gut, vol.53, pp.987-992

D. N. Frank, A. L. St-amand, R. A. Feldman, E. C. Boedeker, N. Harpaz et al., Molecular-phylogenetic characterization of microbial community imbalances in human inflammatory bowel diseases, Proc. Natl. Acad. Sci. U. S. A, vol.104, pp.13780-13785, 2007.

S. Fujimori, A. Tatsuguchi, K. Gudis, T. Kishida, K. Mitsui et al., High dose probiotic and prebiotic cotherapy for remission induction of active Crohn's disease, J. Gastroenterol. Hepatol, vol.22, pp.1199-1204, 2007.

M. Fujiya, N. Ueno, and Y. Kohgo, Probiotic treatments for induction and maintenance of remission in inflammatory bowel diseases: a meta-analysis of randomized controlled trials, Clin. J. Gastroenterol, vol.7, pp.1-13, 2014.

S. Fukuoka and C. M. Nyaruhucha, Expression and functional analysis of rat P23, a gut hormone-inducible isoform of trypsin, reveals its resistance to proteinaceous trypsin inhibitors, Biochim. Biophys. Acta, vol.1588, pp.106-112, 2002.

J. B. Furness, Types of neurons in the enteric nervous system, J. Auton. Nerv. Syst, vol.81, pp.87-96, 2000.

J. B. Furness, The enteric nervous system and neurogastroenterology, Nat. Rev. Gastroenterol. Hepatol, vol.9, pp.286-294, 2012.

J. B. Furness, W. A. Kunze, C. , and N. , Nutrient tasting and signaling mechanisms in the gut. II. The intestine as a sensory organ: neural, endocrine, and immune responses, Am. J. Physiol, vol.277, pp.922-928, 1999.

J. B. Furness, C. Jones, K. Nurgali, C. , and N. , Intrinsic primary afferent neurons and nerve circuits within the intestine, Prog. Neurobiol, vol.72, pp.143-164, 2004.

J. B. Furness, L. R. Rivera, H. Cho, D. M. Bravo, and B. Callaghan, The gut as a sensory organ, Nat. Rev. Gastroenterol. Hepatol, vol.10, pp.729-740, 2013.

P. R. Gaffney, C. T. Doyle, A. Gaffney, J. Hogan, D. P. Hayes et al., Paradoxical response to heparin in 10 patients with ulcerative colitis, Am. J. Gastroenterol, vol.90, pp.220-223, 1995.

H. J. Galipeau, M. Wiepjes, J. Motta, J. D. Schulz, J. Jury et al., Novel role of the serine protease inhibitor elafin in gluten-related disorders, Am. J. Gastroenterol, vol.109, pp.748-756, 2014.
URL : https://hal.archives-ouvertes.fr/hal-01204309

M. Galliano, E. Toulza, N. Jonca, S. L. Gonias, G. Serre et al., Binding of ?2ML1 to the Low Density Lipoprotein Receptor-Related Protein 1 (LRP1) Reveals a New Role for LRP1 in the Human Epidermis, PLoS ONE, vol.3, 2008.

R. L. Gallo and L. V. Hooper, Epithelial antimicrobial defence of the skin and intestine, Nat. Rev. Immunol, vol.12, pp.503-516, 2012.

C. Gao, S. Liu, H. Hu, N. Gao, G. Y. Kim et al., Serine proteases excite myenteric neurons through protease-activated receptors in guinea pig small intestine, Gastroenterology, vol.123, pp.1554-1564, 2002.

V. Garcia-hernandez, M. Quiros, and A. Nusrat, Intestinal epithelial claudins: expression and regulation in homeostasis and inflammation, Ann. N. Y. Acad. Sci, vol.1397, pp.66-79, 2017.

J. Gay, J. Fioramonti, R. Garcia-villar, and L. Buéno, Alterations of intestinal motor responses to various stimuli after Nippostrongylus brasiliensis infection in rats: role of mast cells, Neurogastroenterol. Motil. Off. J. Eur. Gastrointest. Motil. Soc, vol.12, pp.207-214, 2000.

S. A. Gaylord, O. S. Palsson, E. L. Garland, K. R. Faurot, R. S. Coble et al., Mindfulness Training Reduces the Severity of Irritable Bowel Syndrome in Women: Results of a Randomized Controlled Trial, Am. J. Gastroenterol, vol.106, pp.1678-1688, 2011.

K. Gecse, R. Róka, L. Ferrier, M. Leveque, H. Eutamene et al., Increased faecal serine protease activity in diarrhoeic IBS patients: a colonic lumenal factor impairing colonic permeability and sensitivity, Gut, vol.57, pp.591-599, 2008.

B. J. Geerling, P. C. Dagnelie, A. Badart-smook, M. G. Russel, R. W. Stockbrügger et al., Diet as a risk factor for the development of ulcerative colitis, Am. J. Gastroenterol, vol.95, pp.1008-1013, 2000.

F. Gerbe, J. , and P. , Intestinal tuft cells: epithelial sentinels linking luminal cues to the immune system, Mucosal Immunol, vol.9, pp.1353-1359, 2016.
URL : https://hal.archives-ouvertes.fr/hal-01940967

M. D. Gershon, Review article: roles played by 5-hydroxytryptamine in the physiology of the bowel, Aliment. Pharmacol. Ther, vol.13, issue.2, pp.15-30, 1999.

D. Ghosh, E. Porter, B. Shen, S. K. Lee, D. Wilk et al., Paneth cell trypsin is the processing enzyme for human defensin-5, Nat. Immunol, vol.3, pp.583-590, 2002.

L. Gibold, E. Garenaux, G. Dalmasso, C. Gallucci, D. Cia et al., The Vat-AIEC protease promotes crossing of the intestinal mucus layer by Crohn's disease-associated Escherichia coli, Cell. Microbiol, vol.18, pp.617-631, 2016.

J. J. Gillespie, A. R. Wattam, S. A. Cammer, J. L. Gabbard, M. P. Shukla et al., PATRIC: the comprehensive bacterial bioinformatics resource with a focus on human pathogenic species, Infect. Immun, vol.79, pp.4286-4298, 2011.

H. H. Ginzberg, V. Cherapanov, Q. Dong, A. Cantin, C. A. Mcculloch et al., Neutrophil-mediated epithelial injury during transmigration: role of elastase, Am. J. Physiol. Gastrointest. Liver Physiol, vol.281, pp.705-717, 2001.

H. H. Ginzberg, P. T. Shannon, T. Suzuki, O. Hong, E. Vachon et al., Leukocyte elastase induces epithelial apoptosis: role of mitochondial permeability changes and Akt, Am. J. Physiol. Gastrointest. Liver Physiol, vol.287, pp.286-298, 2004.

P. Gionchetti, F. Rizzello, A. Venturi, P. Brigidi, D. Matteuzzi et al., Oral bacteriotherapy as maintenance treatment in patients with chronic pouchitis: a double-blind, placebo-controlled trial, Gastroenterology, vol.119, pp.305-309, 2000.

R. D. Giorgio, B. , and G. , Is irritable bowel syndrome an inflammatory disorder?, Curr. Gastroenterol. Rep, vol.10, pp.385-390, 2008.

B. A. Goldenberg, P. Rawsthorne, and C. N. Bernstein, The utility of 6-thioguanine metabolite levels in managing patients with inflammatory bowel disease, Am. J. Gastroenterol, vol.99, pp.1744-1748, 2004.

P. K. Gopal, J. Prasad, J. Smart, and H. S. Gill, In vitro adherence properties of Lactobacillus rhamnosus DR20 and Bifidobacterium lactis DR10 strains and their antagonistic activity against an enterotoxigenic Escherichia coli, Int. J. Food Microbiol, vol.67, pp.207-216, 2001.

H. A. Gordon and E. Bruckner-kardoss, Effect of normal microbial flora on intestinal surface area, Am. J. Physiol, vol.201, pp.175-178, 1961.

S. M. Greenfield, N. A. Punchard, J. P. Teare, and R. P. Thompson, Review article: the mode of action of the aminosalicylates in inflammatory bowel disease, Aliment. Pharmacol. Ther, vol.7, pp.369-383, 1993.

J. Grimoud, H. Durand, S. De-souza, P. Monsan, F. Ouarné et al., In vitro screening of probiotics and synbiotics according to anti-inflammatory and anti-proliferative effects, Int. J. Food Microbiol, vol.144, pp.42-50, 2010.

W. C. De-groat, I. Nadelhaft, R. J. Milne, A. M. Booth, C. Morgan et al., Organization of the sacral parasympathetic reflex pathways to the urinary bladder and large intestine, J. Auton. Nerv. Syst, vol.3, pp.135-160, 1981.

D. Grundy, Neuroanatomy of visceral nociception: vagal and splanchnic afferent, Gut, vol.51, p.2, 2002.

D. Günzel, Y. , and A. S. , Claudins and the Modulation of Tight Junction Permeability, Physiol. Rev, vol.93, p.525, 2013.

N. Guyot, M. Zani, M. Maurel, S. Dallet-choisy, and T. Moreau, Elafin and its precursor trappin-2 still inhibit neutrophil serine proteinases when they are covalently bound to extracellular matrix proteins by tissue transglutaminase, Biochemistry (Mosc.), vol.44, pp.15610-15618, 2005.

N. Guyot, G. Bergsson, M. W. Butler, C. M. Greene, S. Weldon et al., Functional study of elafin cleaved by Pseudomonas aeruginosa metalloproteinases, Biol. Chem, vol.391, pp.705-716, 2010.

K. Gwee, Irritable bowel syndrome in developing countries-a disorder of civilization or colonization?, Neurogastroenterol. Motil, vol.17, pp.317-324, 2005.

S. Haerteis, A. Krappitz, M. Krappitz, J. E. Murphy, M. Bertog et al., Proteolytic activation of the human epithelial sodium channel by trypsin IV and trypsin I involves distinct cleavage sites, J. Biol. Chem, vol.289, pp.19067-19078, 2014.

A. F. Hagel, T. Derossi, Y. Zopf, P. Konturek, W. Dauth et al., Mast cell tryptase levels in gut mucosa in patients with gastrointestinal symptoms caused by food allergy, Int. Arch. Allergy Immunol, vol.160, pp.350-355, 2013.

E. Hait, L. Hait, A. Bousvaros, and R. Grand, Pediatric inflammatory bowel disease: what children can teach adults, Inflamm. Bowel Dis, vol.11, pp.519-527, 2005.

Å. Håkansson, N. Tormo-badia, A. Baridi, J. Xu, G. Molin et al., Immunological alteration and changes of gut microbiota after dextran sulfate sodium (DSS) administration in mice, Clin. Exp. Med, vol.15, pp.107-120, 2015.

H. E. Hamm, How activated receptors couple to G proteins, Proc. Natl. Acad. Sci. U. S. A, vol.98, pp.4819-4821, 2001.

J. Hampe, K. Heymann, M. Krawczak, and S. Schreiber, Association of inflammatory bowel disease with indicators for childhood antigen and infection exposure, Int. J. Colorectal Dis, vol.18, pp.413-417, 2003.

S. B. Hanauer and W. Sandborn, and Practice Parameters Committee of the American College of, Am. J. Gastroenterol, vol.96, pp.635-643, 2001.

W. Hans, J. Schölmerich, V. Gross, and W. Falk, The role of the resident intestinal flora in acute and chronic dextran sulfate sodium-induced colitis in mice, Eur. J. Gastroenterol. Hepatol, vol.12, pp.267-273, 2000.

R. Hansen, R. K. Russell, C. Reiff, P. Louis, F. Mcintosh et al., Microbiota of de-novo pediatric IBD: increased Faecalibacterium prausnitzii and reduced bacterial diversity in Crohn's but not in ulcerative colitis, Am. J. Gastroenterol, vol.107, pp.1913-1922, 2012.

G. C. Hansson, J. , and M. E. , The inner of the two Muc2 mucin-dependent mucus layers in colon is devoid of bacteria, Gut Microbes, vol.1, pp.51-54, 2010.

K. Hara, Y. Saito, Y. Kirihara, Y. Yamada, S. Sakura et al., The interaction of antinociceptive effects of morphine and GABA receptor agonists within the rat spinal cord, Anesth. Analg, vol.89, pp.422-427, 1999.

J. Harder, R. Gläser, and J. Schröder, Review: Human antimicrobial proteins-effectors of innate immunity, J. Endotoxin Res, vol.13, pp.317-338, 2007.

G. Harris, R. Kuolee, C. , and W. , Role of Toll-like receptors in health and diseases of gastrointestinal tract, World J. Gastroenterol, vol.12, pp.2149-2160, 2006.

A. L. Hart, H. O. Al-hassi, R. J. Rigby, S. J. Bell, A. V. Emmanuel et al., Characteristics of intestinal dendritic cells in inflammatory bowel diseases, Gastroenterology, vol.129, pp.50-65, 2005.

S. Z. Hasnain, M. A. Mcguckin, R. K. Grencis, T. , and D. J. , Serine protease(s) secreted by the nematode Trichuris muris degrade the mucus barrier, PLoS Negl. Trop. Dis, vol.6, 1856.

A. Hayday, E. Theodoridis, E. Ramsburg, and J. Shires, Intraepithelial lymphocytes: exploring the Third Way in immunology, Nat. Immunol, vol.2, pp.997-1003, 2001.

S. He, Q. Peng, and A. F. Walls, Potent induction of a neutrophil and eosinophilrich infiltrate in vivo by human mast cell tryptase: selective enhancement of eosinophil recruitment by histamine, J. Immunol. Baltim. Md, vol.159, pp.6216-6225, 1950.

K. A. Heel, R. D. Mccauley, J. M. Papadimitriou, and J. C. Hall, REVIEW: Peyer's patches, J. Gastroenterol. Hepatol, vol.12, pp.122-136, 1997.

M. Heitkemper, M. Jarrett, K. C. Cain, R. Burr, R. L. Levy et al., , 2001.

, Autonomic nervous system function in women with irritable bowel syndrome, Dig. Dis. Sci, vol.46, pp.1276-1284

I. R. Henderson, J. Czeczulin, C. Eslava, F. Noriega, and J. P. Nataro, Characterization of pic, a secreted protease of Shigella flexneri and enteroaggregative Escherichia coli, Infect. Immun, vol.67, pp.5587-5596, 1999.

J. F. Henrich, K. Knittle, V. De-gucht, S. Warren, S. U. Dombrowski et al., Identifying effective techniques within psychological treatments for irritable bowel syndrome: A meta-analysis, J. Psychosom. Res, vol.78, pp.205-222, 2015.

N. A. Hering, M. Fromm, and J. Schulzke, Determinants of colonic barrier function in inflammatory bowel disease and potential therapeutics, J. Physiol, vol.590, pp.1035-1044, 2012.

M. L. Hermiston, G. , and J. I. , In vivo analysis of cadherin function in the mouse intestinal epithelium: essential roles in adhesion, maintenance of differentiation, and regulation of programmed cell death, J. Cell Biol, vol.129, pp.489-506, 1995.

J. N. Higaki, B. W. Gibson, and C. S. Craik, Evolution of catalysis in the serine proteases, Cold Spring Harb. Symp. Quant. Biol, vol.52, pp.615-621, 1987.

K. Hod, A. D. Sperber, Y. Ron, M. Boaz, R. Dickman et al., A double-blind, placebo-controlled study to assess the effect of a probiotic mixture on symptoms and inflammatory markers in women with diarrheapredominant IBS, Neurogastroenterol. Motil. Off. J. Eur. Gastrointest. Motil. Soc, vol.29, 2017.

D. Höfer and D. Drenckhahn, Cytoskeletal markers allowing discrimination between brush cells and other epithelial cells of the gut including enteroendocrine cells, Histochem. Cell Biol, vol.105, pp.405-412, 1996.

W. Hoffmann, Trefoil factor family (TFF) peptides: regulators of mucosal regeneration and repair, and more, Peptides, vol.25, pp.727-730, 2004.

A. Hoffmann, T. H. Leung, and D. Baltimore, Genetic analysis of NF-kappaB/Rel transcription factors defines functional specificities, EMBO J, vol.22, pp.5530-5539, 2003.

M. D. Hollenberg, M. Saifeddine, S. Sandhu, S. Houle, and N. Vergnolle, , 2004.

, Proteinase-activated receptor-4: evaluation of tethered ligand-derived peptides as probes for receptor function and as inflammatory agonists in vivo, Br. J. Pharmacol, vol.143, p.443

M. D. Hollenberg, K. Mihara, D. Polley, J. Y. Suen, A. Han et al., Biased signalling and proteinase-activated receptors (PARs): targeting inflammatory disease, Br. J. Pharmacol, vol.171, pp.1180-1194, 2014.

N. Holmén, S. Isaksson, M. Simrén, H. Sjövall, and L. Öhman, CD4+CD25+ regulatory T cells in irritable bowel syndrome patients, Neurogastroenterol. Motil, vol.19, pp.119-125, 2007.

C. R. Homer, A. L. Richmond, N. A. Rebert, J. Achkar, and C. Mcdonald, ATG16L1 and NOD2 interact in an autophagy-dependent antibacterial pathway implicated in Crohn's disease pathogenesis, Gastroenterology, vol.139, pp.1-2, 1641.

S. Hosomi, A. Kaser, and R. S. Blumberg, Role of endoplasmic reticulum stress and autophagy as interlinking pathways in the pathogenesis of inflammatory bowel disease, Curr. Opin. Gastroenterol, vol.31, pp.81-88, 2015.

S. Houle, M. D. Papez, M. Ferazzini, M. D. Hollenberg, and N. Vergnolle, , 2005.

, Neutrophils and the kallikrein-kinin system in proteinase-activated receptor 4-mediated inflammation in rodents, Br. J. Pharmacol, vol.146, pp.670-678

Y. Huang, C. , and Z. , Inflammatory bowel disease related innate immunity and adaptive immunity, Am. J. Transl. Res, vol.8, pp.2490-2497, 2016.

T. Hudcovic, J. Kolinska, J. Klepetar, R. Stepankova, T. Rezanka et al., Protective effect of Clostridium tyrobutyricum in acute dextran sodium sulphate-induced colitis: differential regulation of tumour necrosis factor-? and interleukin-18 in BALB/c and severe combined immunodeficiency mice, Clin. Exp. Immunol, vol.167, pp.356-365, 2012.

I. L. Huibregtse, A. U. Van-lent, and S. J. Van-deventer, Immunopathogenesis of IBD: insufficient suppressor function in the gut?, Gut, vol.56, pp.584-592, 2007.

J. A. Huntington, R. J. Read, and R. W. Carrell, Structure of a serpin-protease complex shows inhibition by deformation, Nature, vol.407, pp.923-926, 2000.

E. Hyun, P. Andrade-gordon, M. Steinhoff, and N. Vergnolle, Protease-activated receptor-2 activation: a major actor in intestinal inflammation, Gut, vol.57, pp.1222-1229, 2008.

V. Iablokov, C. L. Hirota, M. A. Peplowski, R. Ramachandran, K. Mihara et al., Proteinase-activated receptor 2 (PAR2) decreases apoptosis in colonic epithelial cells, J. Biol. Chem, vol.289, pp.34366-34377, 2014.

A. Tjonneland, K. Overvad, M. M. Bergmann, G. Nagel, J. Linseisen et al., Linoleic acid, a dietary n-6 polyunsaturated fatty acid, and the aetiology of ulcerative colitis: a nested case-control study within a European prospective cohort study, IBD in EPIC Study Investigators, vol.58, pp.1606-1611, 2009.

S. Ida, N. Ozaki, K. Araki, K. Hirashima, Y. Zaitsu et al., SPINK1 Status in Colorectal Cancer, Impact on Proliferation, and Role in Colitis-Associated Cancer, vol.13, pp.1130-1138, 2015.

M. Iizuka and S. Konno, Wound healing of intestinal epithelial cells, World J. Gastroenterol. WJG, vol.17, pp.2161-2171, 2011.

H. Ireland, C. Houghton, L. Howard, and D. J. Winton, Cellular inheritance of a Cre-activated reporter gene to determine Paneth cell longevity in the murine small intestine, Dev. Dyn. Off. Publ. Am. Assoc. Anat, vol.233, pp.1332-1336, 2005.

C. Jacob, P. Yang, D. Darmoul, S. Amadesi, T. Saito et al., Mast cell tryptase controls paracellular permeability of the intestine. Role of protease-activated receptor 2 and beta-arrestins, J. Biol. Chem, vol.280, pp.31936-31948, 2005.

S. M. Jandhyala, R. Talukdar, C. Subramanyam, H. Vuyyuru, M. Sasikala et al., Role of the normal gut microbiota, World J. Gastroenterol. WJG, vol.21, pp.8787-8803, 2015.

A. Jarry, L. Dorso, V. Gratio, M. Forgue-lafitte, M. Laburthe et al., PAR-2 activation increases human intestinal mucin secretion through EGFR transactivation, Biochem. Biophys. Res. Commun, vol.364, pp.689-694, 2007.

V. J. Jasinghe, E. A. Peyrotte, A. F. Meyers, N. Gajanayaka, T. B. Ball et al., Human rElafin Inhibits HIV-1 Replication in Its Natural Target Cells, BioResearch Open Access, vol.2, pp.128-137, 2013.

Z. Jevnikar, N. Obermajer, M. Bogyo, and J. Kos, The role of cathepsin X in the migration and invasiveness of T lymphocytes, J. Cell Sci, vol.121, pp.2652-2661, 2008.

M. E. Johansson, J. K. Gustafsson, J. Holmén-larsson, K. S. Jabbar, L. Xia et al., Bacteria penetrate the normally impenetrable inner colon mucus layer in both murine colitis models and patients with ulcerative colitis, Gut, vol.63, pp.281-291, 2014.

L. Jostins, S. Ripke, R. K. Weersma, R. H. Duerr, D. P. Mcgovern et al., Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease, Nature, vol.491, pp.119-124, 2012.

V. Julia, O. Morteau, and L. Buéno, Involvement of neurokinin 1 and 2 receptors in viscerosensitive response to rectal distension in rats, Gastroenterology, vol.107, pp.94-102, 1994.

V. Julia, T. Mezzasalma, and L. Buéno, Influence of bradykinin in gastrointestinal disorders and visceral pain induced by acute or chronic inflammation in rats, Dig. Dis. Sci, vol.40, pp.1913-1921, 1995.

J. and D. , TRP channels and pain, Annu. Rev. Cell Dev. Biol, vol.29, pp.355-384, 2013.

S. Kagota, K. Maruyama, and J. J. Mcguire, Characterization and Functions of Protease-Activated Receptor 2 in Obesity, Diabetes, and Metabolic Syndrome: A Systematic Review, BioMed Res. Int, p.3130496, 2016.

M. L. Kahn, S. R. Hammes, C. Botka, and S. R. Coughlin, Gene and locus structure and chromosomal localization of the protease-activated receptor gene family, J. Biol. Chem, vol.273, pp.23290-23296, 1998.

M. Kanazawa, Y. Endo, W. E. Whitehead, M. Kano, M. Hongo et al., distress. Dig. Dis. Sci, vol.49, pp.1046-1053, 2004.

N. C. Kaneider, A. J. Leger, A. Agarwal, N. Nguyen, G. Perides et al., Role reversal" for the receptor PAR1 in sepsis-induced vascular damage, Nat. Immunol, vol.8, pp.1303-1312, 2007.

S. Kang, T. Okuno, N. Takegahara, H. Takamatsu, S. Nojima et al., Intestinal epithelial cell-derived semaphorin 7A negatively regulates development of colitis via ?v?1 integrin, J. Immunol. Baltim. Md, vol.188, pp.1108-1116, 1950.

A. Kaser, A. Lee, A. Franke, J. N. Glickman, S. Zeissig et al., XBP1 links ER stress to intestinal inflammation and confers genetic risk for human inflammatory bowel disease, Cell, vol.134, pp.743-756, 2008.

A. Kaser, S. Zeissig, and R. S. Blumberg, Inflammatory bowel disease, Annu. Rev. Immunol, vol.28, pp.573-621, 2010.

Y. Kawahito, H. Sano, M. Kawata, K. Yuri, S. Mukai et al., Local secretion of corticotropin-releasing hormone by enterochromaffin cells in human colon, Gastroenterology, vol.106, pp.859-865, 1994.

L. A. Kazal, D. S. Spicer, and R. A. Brahinsky, Isolation of a crystalline trypsin inhibitor-anticoagulant protein from pancreas, J. Am. Chem. Soc, vol.70, pp.3034-3040, 1948.

A. P. Kerckhoffs, J. J. Ter-linde, L. M. Akkermans, and M. Samsom, , 2008.

, Trypsinogen IV, serotonin transporter transcript levels and serotonin content are increased in small intestine of irritable bowel syndrome patients, Neurogastroenterol. Motil, vol.20, pp.900-907

S. Khaldi, G. Gargala, L. Le-goff, S. Parey, A. Francois et al., Cryptosporidium parvum isolate-dependent postinfectious jejunal hypersensitivity and mast cell accumulation in an immunocompetent rat model, Infect. Immun, vol.77, pp.5163-5169, 2009.
URL : https://hal.archives-ouvertes.fr/hal-00489341

K. J. Khan, T. A. Ullman, A. C. Ford, M. T. Abreu, A. Abadir et al., Antibiotic therapy in inflammatory bowel disease: a systematic review and meta-analysis, Am. J. Gastroenterol, vol.106, pp.661-673, 2011.

Y. S. Kim and S. B. Ho, Intestinal goblet cells and mucins in health and disease: recent insights and progress, Curr. Gastroenterol. Rep, vol.12, pp.319-330, 2010.

J. J. Kim, M. S. Shajib, M. M. Manocha, and W. I. Khan, Investigating Intestinal Inflammation in DSS-induced Model of IBD, J. Vis. Exp. JoVE, 2012.

M. Kiss, Z. Czimmerer, and L. Nagy, The role of lipid-activated nuclear receptors in shaping macrophage and dendritic cell function: From physiology to pathology, J. Allergy Clin. Immunol, vol.132, pp.264-286, 2013.

E. Klement, R. V. Cohen, J. Boxman, A. Joseph, R. et al., Breastfeeding and risk of inflammatory bowel disease: a systematic review with meta-analysis, Am. J. Clin. Nutr, vol.80, pp.1342-1352, 2004.

Z. Kmie?, Cytokines in inflammatory bowel disease, Arch. Immunol. Ther. Exp. (Warsz.), vol.46, pp.143-155, 1998.

W. Knecht, G. S. Cottrell, S. Amadesi, J. Mohlin, A. Skåregärde et al., Trypsin IV or Mesotrypsin and p23 Cleave Protease-activated Receptors 1 and 2 to Induce Inflammation and Hyperalgesia, J. Biol. Chem, vol.282, pp.26089-26100, 2007.

D. R. Knighton, T. K. Hunt, H. Scheuenstuhl, B. J. Halliday, Z. Werb et al., Oxygen tension regulates the expression of angiogenesis factor by macrophages, Science, vol.221, pp.1283-1285, 1983.

N. Kolli and S. C. Garman, Proteolytic Activation of Human Cathepsin A, J. Biol. Chem, vol.289, pp.11592-11600, 2014.

J. König, J. Wells, P. D. Cani, C. L. García-ródenas, T. Macdonald et al., Human Intestinal Barrier Function in Health and Disease, Clin. Transl. Gastroenterol, vol.7, p.196, 2016.

A. Kornbluth and D. B. Sachar, Ulcerative Colitis Practice Guidelines in Adults (Update): American College of Gastroenterology, Practice Parameters Committee, Am. J. Gastroenterol, vol.99, pp.1371-1385, 2004.

I. E. Koutroubakis, I. G. Vlachonikolis, and E. A. Kouroumalis, Role of appendicitis and appendectomy in the pathogenesis of ulcerative colitis: a critical review, Inflamm. Bowel Dis, vol.8, pp.277-286, 2002.

J. P. Kraehenbuhl and M. R. Neutra, Molecular and cellular basis of immune protection of mucosal surfaces, Physiol. Rev, vol.72, pp.853-879, 1992.

L. Krogius-kurikka, A. Lyra, E. Malinen, J. Aarnikunnas, J. Tuimala et al., Microbial community analysis reveals high level phylogenetic alterations in the overall gastrointestinal microbiota of diarrhoea-predominant irritable bowel syndrome sufferers, BMC Gastroenterol, vol.9, p.95, 2009.

J. H. Kurata, S. Kantor-fish, H. Frankl, P. Godby, and C. M. Vadheim, Crohn's disease among ethnic groups in a large health maintenance organization, Gastroenterology, vol.102, pp.1940-1948, 1992.

M. Laforge, N. Bidère, S. Carmona, A. Devocelle, B. Charpentier et al., Apoptotic death concurrent with CD3 stimulation in primary human CD8+ T lymphocytes: a role for endogenous granzyme B, J. Immunol. Baltim. Md, vol.176, pp.3966-3977, 1950.

J. M. Laird, C. Roza, C. De-felipe, S. P. Hunt, C. et al., Role of central and peripheral tachykinin NK1 receptors in capsaicin-induced pain and hyperalgesia in mice, Pain, vol.90, pp.97-103, 2001.

J. M. Laird, L. Martinez-caro, E. Garcia-nicas, C. , and F. , A new model of visceral pain and referred hyperalgesia in the mouse, Pain, vol.92, pp.335-342, 2001.

D. A. Lane, H. Philippou, H. , and J. A. , Directing thrombin, Blood, vol.106, pp.2605-2612, 2005.

J. Langhorst, S. Elsenbruch, J. Koelzer, A. Rueffer, A. Michalsen et al., Noninvasive markers in the assessment of intestinal inflammation in inflammatory bowel diseases: performance of fecal lactoferrin, calprotectin, and PMN-elastase, CRP, and clinical indices, Am. J. Gastroenterol, vol.103, pp.162-169, 2008.

M. Larauche, G. Gourcerol, L. Wang, K. Pambukchian, S. Brunnhuber et al., Cortagine, a CRF1 agonist, induces stresslike alterations of colonic function and visceral hypersensitivity in rodents primarily through peripheral pathways, Am. J. Physiol.-Gastrointest. Liver Physiol, vol.297, p.215, 2009.

M. Larauche, A. Mulak, and Y. Taché, Stress-Related Alterations of Visceral Sensation: Animal Models for Irritable Bowel Syndrome Study, J. Neurogastroenterol. Motil, vol.17, p.213, 2011.

M. Larauche, A. Mulak, and Y. Taché, Stress and visceral pain: from animal models to clinical therapies, Exp. Neurol, vol.233, p.49, 2012.

R. H. Law, Q. Zhang, S. Mcgowan, A. M. Buckle, G. A. Silverman et al., An overview of the serpin superfamily, Genome Biol, vol.7, p.216, 2006.

A. M. Lechner, I. Assfalg-machleidt, S. Zahler, M. Stoeckelhuber, W. Machleidt et al., RGD-dependent binding of procathepsin X to integrin alphavbeta3 mediates cell-adhesive properties, J. Biol. Chem, vol.281, pp.39588-39597, 2006.

S. H. Lee, Intestinal Permeability Regulation by Tight Junction: Implication on, Inflammatory Bowel Diseases. Intest. Res, vol.13, p.11, 2015.

J. Lee, J. Mo, K. Katakura, I. Alkalay, A. N. Rucker et al., Maintenance of colonic homeostasis by distinctive apical TLR9 signalling in intestinal epithelial cells, Nat. Cell Biol, vol.8, pp.1327-1336, 2006.

K. J. Lee, J. H. Kim, and S. W. Cho, Gabapentin reduces rectal mechanosensitivity and increases rectal compliance in patients with diarrhoea-predominant irritable bowel syndrome, Aliment. Pharmacol. Ther, vol.22, pp.981-988, 2005.

K. J. Lee, Y. B. Kim, J. H. Kim, H. C. Kwon, D. K. Kim et al., The alteration of enterochromaffin cell, mast cell, and lamina propria T lymphocyte numbers in irritable bowel syndrome and its relationship with psychological factors, J. Gastroenterol. Hepatol, vol.23, pp.1689-1694, 2008.

J. S. Leeds, A. D. Hopper, R. Sidhu, A. Simmonette, N. Azadbakht et al., Some patients with irritable bowel syndrome may have exocrine pancreatic insufficiency, Clin. Gastroenterol. Hepatol. Off. Clin. Pract. J. Am. Gastroenterol. Assoc, vol.8, pp.433-438, 2010.

T. Lembo, V. Plourde, Z. Shui, S. Fullerton, H. Mertz et al., Effects of the corticotropin-releasing factor (CRF) on rectal afferent nerves in humans, Neurogastroenterol. Motil. Off. J. Eur. Gastrointest. Motil. Soc, vol.8, pp.9-18, 1996.

S. Lesko, I. Wessler, G. Gäbel, C. Petto, P. et al., Cholinergic modulation of epithelial integrity in the proximal colon of pigs, Cells Tissues Organs, vol.197, pp.411-420, 2013.

B. Levine, N. Mizushima, and H. W. Virgin, Autophagy in immunity and inflammation, Nature, vol.469, pp.323-335, 2011.

R. L. Levy, K. R. Jones, W. E. Whitehead, S. I. Feld, N. J. Talley et al., Irritable bowel syndrome in twins: Heredity and social learning both contribute to etiology, Gastroenterology, vol.121, pp.799-804, 2001.

W. Li, H. Wang, C. Kuang, J. Zhu, Y. Yu et al., An essential role for the Id1/PI3K/Akt/NFkB/survivin signalling pathway in promoting the proliferation of endothelial progenitor cells in vitro, Mol. Cell. Biochem, vol.363, pp.135-145, 2012.

S. Lichtiger, D. H. Present, A. Kornbluth, I. Gelernt, J. Bauer et al., Cyclosporine in severe ulcerative colitis refractory to steroid therapy, N. Engl. J. Med, vol.330, pp.1841-1845, 1994.

M. E. Lidell, D. M. Moncada, K. Chadee, and G. C. Hansson, Entamoeba histolytica cysteine proteases cleave the MUC2 mucin in its C-terminal domain and dissolve the protective colonic mucus gel, Proc. Natl. Acad. Sci. U. S. A, vol.103, pp.9298-9303, 2006.

D. R. Linden, B. P. Manning, N. W. Bunnett, and G. M. Mawe, Agonists of proteinase-activated receptor 2 excite guinea pig ileal myenteric neurons, Eur. J. Pharmacol, vol.431, pp.311-314, 2001.

M. J. Lodes, Y. Cong, C. O. Elson, R. Mohamath, C. J. Landers et al., Bacterial flagellin is a dominant antigen in Crohn disease, J. Clin. Invest, vol.113, pp.1296-1306, 2004.

E. V. Loftus, P. Schoenfeld, and W. J. Sandborn, The epidemiology and natural history of Crohn's disease in population-based patient cohorts from North America: a systematic review, Aliment. Pharmacol. Ther, vol.16, pp.51-60, 2002.

E. Louis, A. Collard, A. F. Oger, E. Degroote, F. A. Aboul-nasr-el-yafi et al., Behaviour of Crohn's disease according to the Vienna classification: changing pattern over the course of the disease, Gut, vol.49, pp.777-782, 2001.

R. M. Lovell and A. C. Ford, Global Prevalence of and Risk Factors for Irritable Bowel Syndrome: A Meta-analysis, Clin. Gastroenterol. Hepatol, vol.10, pp.712-721, 2012.

S. Ludidi, Z. Mujagic, D. Jonkers, D. Keszthelyi, M. Hesselink et al., Markers for visceral hypersensitivity in patients with irritable bowel syndrome, Neurogastroenterol. Motil, vol.26, pp.1104-1111, 2014.

S. Ludidi, D. Jonkers, E. Elamin, H. Pieters, E. Schaepkens et al., The Intestinal Barrier in Irritable Bowel Syndrome: Subtype-Specific Effects of the Systemic Compartment in an, In Vitro Model. PLOS ONE, vol.10, 2015.

K. Luo and S. S. Cao, Endoplasmic Reticulum Stress in Intestinal Epithelial Cell Function and Inflammatory Bowel Disease, Gastroenterol. Res. Pract, 2015.

G. T. Macfarlane and S. Macfarlane, Fermentation in the human large intestine: its physiologic consequences and the potential contribution of prebiotics, J. Clin. Gastroenterol, vol.45, pp.120-127, 2011.

S. Macfarlane and G. T. Macfarlane, Regulation of short-chain fatty acid production, Proc. Nutr. Soc, vol.62, pp.67-72, 2003.

D. R. Mack, S. Michail, S. Wei, L. Mcdougall, and M. A. Hollingsworth, Probiotics inhibit enteropathogenic E. coli adherence in vitro by inducing intestinal mucin gene expression, Am. J. Physiol, vol.276, pp.941-950, 1999.

J. Macsharry, L. O'mahony, A. Fanning, E. Bairead, G. Sherlock et al., Mucosal cytokine imbalance in irritable bowel syndrome, Scand. J. Gastroenterol, vol.43, pp.1467-1476, 2008.

H. Maekawa and D. M. Tollefsen, Role of the Proposed Serpin-Enzyme Complex Receptor Recognition Site in Binding and Internalization of Thrombin-Heparin Cofactor II Complexes by Hepatocytes, J. Biol. Chem, vol.271, pp.18604-18609, 1996.

C. Maillot, M. Million, J. Y. Wei, A. Gauthier, and Y. Taché, Peripheral corticotropin-releasing factor and stress-stimulated colonic motor activity involve type 1 receptor in rats, Gastroenterology, vol.119, pp.1569-1579, 2000.

W. Maison, I. Schlemminger, O. Westerhoff, and J. Martens, Modified PNAs: a simple method for the synthesis of monomeric building blocks, Bioorg. Med. Chem. Lett, vol.9, pp.581-584, 1999.

P. L. Mäkinen, D. B. Clewell, F. An, and K. K. Mäkinen, Purification and substrate specificity of a strongly hydrophobic extracellular metalloendopeptidase ("gelatinase") from Streptococcus faecalis (strain 0G1-10), J. Biol. Chem, vol.264, pp.3325-3334, 1989.

P. Mallon, D. Mckay, S. Kirk, G. , and K. , Probiotics for induction of remission in ulcerative colitis, Cochrane Database Syst. Rev. CD005573, 2007.

S. M. Man, N. O. Kaakoush, M. , and H. M. , The role of bacteria and patternrecognition receptors in Crohn's disease, Nat. Rev. Gastroenterol. Hepatol, vol.8, pp.152-168, 2011.

J. Mankertz, M. Amasheh, S. M. Krug, A. Fromm, S. Amasheh et al., TNFalpha up-regulates claudin-2 expression in epithelial HT-29/B6 cells via phosphatidylinositol-3-kinase signaling, Cell Tissue Res, vol.336, pp.67-77, 2009.

P. Mansueto, A. D'alcamo, A. Seidita, C. , and A. , Food allergy in irritable bowel syndrome: The case of non-celiac wheat sensitivity, World J. Gastroenterol. WJG, vol.21, p.7089, 2015.

N. J. Mantis, C. R. Mcguinness, O. Sonuyi, G. Edwards, and S. A. Farrant, , 2006.

, Immunoglobulin A antibodies against ricin A and B subunits protect epithelial cells from ricin intoxication, Infect. Immun, vol.74, pp.3455-3462

T. Marchbank, A. Mahmood, A. J. Fitzgerald, J. Domin, M. Butler et al., Human pancreatic secretory trypsin inhibitor stabilizes intestinal mucosa against noxious agents, Am. J. Pathol, vol.171, pp.1462-1473, 2007.

F. Marger, A. Gelot, A. Alloui, J. Matricon, J. F. Ferrer et al., T-type calcium channels contribute to colonic hypersensitivity in a rat model of irritable bowel syndrome, Proc. Natl. Acad. Sci. U. S. A, vol.108, pp.11268-11273, 2011.

L. Marín, E. M. Miguélez, C. J. Villar, and F. Lombó, Bioavailability of dietary polyphenols and gut microbiota metabolism: antimicrobial properties, BioMed Res. Int, p.905215, 2015.

K. Matsuoka and T. Kanai, The gut microbiota and inflammatory bowel disease, Semin. Immunopathol, vol.37, pp.47-55, 2015.

H. Matthes, T. Krummenerl, M. Giensch, C. Wolff, and J. Schulze, Clinical trial: probiotic treatment of acute distal ulcerative colitis with rectally administered Escherichia coli Nissle 1917 (EcN), BMC Complement. Altern. Med, vol.10, p.13, 2010.

J. Maul, C. Loddenkemper, P. Mundt, E. Berg, T. Giese et al., Peripheral and intestinal regulatory CD4+ CD25(high) T cells in inflammatory bowel disease, Gastroenterology, vol.128, pp.1868-1878, 2005.

J. E. Mawdsley and D. S. Rampton, Psychological stress in IBD: new insights into pathogenic and therapeutic implications, Gut, vol.54, pp.1481-1491, 2005.

E. A. Mayer, The neurobiology of stress and gastrointestinal disease, Gut, vol.47, pp.861-869, 2000.

E. A. Mayer and G. F. Gebhart, Basic and clinical aspects of visceral hyperalgesia, Gastroenterology, vol.107, pp.271-293, 1994.

L. Mayer and D. Eisenhardt, Lack of induction of suppressor T cells by intestinal epithelial cells from patients with inflammatory bowel disease, J. Clin. Invest, vol.86, pp.1255-1260, 1990.

S. K. Mazmanian, J. L. Round, and D. L. Kasper, A microbial symbiosis factor prevents intestinal inflammatory disease, Nature, vol.453, pp.620-625, 2008.

J. Mcgrath, J. W. Mcdonald, and J. K. Macdonald, Transdermal nicotine for induction of remission in ulcerative colitis, Cochrane Database Syst. Rev. CD004722, 2004.

P. G. Mclean, C. Picard, R. Garcia-villar, R. Ducos-de-lahitte, J. Moré et al., Role of kinin B1 and B2 receptors and mast cells in post intestinal infection-induced hypersensitivity to distension, Neurogastroenterol. Motil. Off. J. Eur. Gastrointest. Motil. Soc, vol.10, pp.499-508, 1998.

S. B. Mcmahon, W. B. Cafferty, and F. Marchand, Immune and glial cell factors as pain mediators and modulators, Exp. Neurol, vol.192, pp.444-462, 2005.

J. W. Mcmichael, A. Roghanian, L. Jiang, R. Ramage, and J. Sallenave, The antimicrobial antiproteinase elafin binds to lipopolysaccharide and modulates macrophage responses, Am. J. Respir. Cell Mol. Biol, vol.32, pp.443-452, 2005.

G. A. Mcquibban, J. Gong, J. P. Wong, J. L. Wallace, I. Clark-lewis et al., Matrix metalloproteinase processing of monocyte chemoattractant proteins generates CC chemokine receptor antagonists with anti-inflammatory properties in vivo, Blood, vol.100, pp.1160-1167, 2002.

R. Medzhitov, Origin and physiological roles of inflammation, Nature, vol.454, pp.428-435, 2008.

T. R. Mempel, S. E. Henrickson, V. Andrian, and U. H. , T-cell priming by dendritic cells in lymph nodes occurs in three distinct phases, Nature, vol.427, pp.154-159, 2004.

H. Mertz, B. Naliboff, J. Munakata, N. Niazi, and E. A. Mayer, Altered rectal perception is a biological marker of patients with irritable bowel syndrome, Gastroenterology, vol.109, pp.40-52, 1995.

U. Meyer-hoffert, J. Wingertszahn, and O. Wiedow, Human leukocyte elastase induces keratinocyte proliferation by epidermal growth factor receptor activation, J. Invest. Dermatol, vol.123, pp.338-345, 2004.

D. Meynard, V. Vaja, C. C. Sun, E. Corradini, S. Chen et al., Regulation of TMPRSS6 by BMP6 and iron in human cells and mice, Blood, vol.118, pp.747-756, 2011.

S. Michlewska, I. Dransfield, I. L. Megson, and A. G. Rossi, Macrophage phagocytosis of apoptotic neutrophils is critically regulated by the opposing actions of pro-inflammatory and anti-inflammatory agents: key role for TNF-alpha, FASEB J. Off. Publ. Fed. Am. Soc. Exp. Biol, vol.23, pp.844-854, 2009.

P. Middel, D. Raddatz, B. Gunawan, F. Haller, and H. Radzun, Increased number of mature dendritic cells in Crohn's disease: evidence for a chemokine mediated retention mechanism, Gut, vol.55, pp.220-227, 2006.

K. Mihara, R. Ramachandran, M. Saifeddine, K. K. Hansen, B. Renaux et al., Thrombin-Mediated Direct Activation of Proteinase-Activated Receptor-2: Another Target for Thrombin Signaling, Mol. Pharmacol, vol.89, pp.606-614, 2016.

A. Minn, M. Schubert, W. F. Neiss, and B. Müller-hill, Enhanced GFAP expression in astrocytes of transgenic mice expressing the human brain-specific trypsinogen IV, Glia, vol.22, pp.338-347, 1998.

J. Miranda-bautista, C. De-gracia-fernández, M. López-ibáñez, M. Barrientos, A. Gallomoltó et al., Lipid Profile in Inflammatory Bowel Disease Patients on Anti-TNF? Therapy, vol.60, pp.2130-2135, 2015.

M. Miyai, Y. Matsumoto, H. Yamanishi, M. Yamamoto-tanaka, R. Tsuboi et al., Keratinocyte-Specific Mesotrypsin Contributes to the Desquamation Process via Kallikrein Activation and LEKTI Degradation, J. Invest. Dermatol, vol.134, pp.1665-1674, 2014.

F. Molinié, C. Gower-rousseau, T. Yzet, V. Merle, B. Grandbastien et al., Opposite evolution in incidence of Crohn's disease and ulcerative colitis in Northern France, Gut, vol.53, pp.843-848, 1988.

N. A. Molodecky, I. S. Soon, D. M. Rabi, W. A. Ghali, M. Ferris et al., Increasing incidence and prevalence of the inflammatory bowel diseases with time, based on systematic review, Gastroenterology, vol.142, pp.46-54, 2012.

R. D. Moloney, S. M. O'mahony, T. G. Dinan, and J. F. Cryan, Stress-induced visceral pain: toward animal models of irritable-bowel syndrome and associated comorbidities, Front. Psychiatry, vol.6, p.15, 2015.

G. Monteleone, I. Monteleone, D. Fina, P. Vavassori, . Del-vecchio et al., , 2005.

, T-helper cell type I signaling and interferon-gamma production in Crohn's disease, Gastroenterology, vol.128, pp.687-694

C. A. Moore, S. K. Milano, and J. L. Benovic, Regulation of receptor trafficking by GRKs and arrestins, Annu. Rev. Physiol, vol.69, pp.451-482, 2007.

C. Moret and M. Briley, Antidepressants in the treatment of fibromyalgia, Neuropsychiatr. Dis. Treat, vol.2, p.537, 2006.

G. P. Morris, P. L. Beck, M. S. Herridge, W. T. Depew, M. R. Szewczuk et al., Hapten-induced model of chronic inflammation and ulceration in the rat colon, Gastroenterology, vol.96, pp.795-803, 1989.

A. Morris-yates, N. J. Talley, P. M. Boyce, S. Nandurkar, and G. Andrews, Evidence of a genetic contribution to functional bowel disorder, Am. J. Gastroenterol, vol.93, pp.1311-1317, 1998.

O. Morteau, T. Hachet, M. Caussette, and L. Bueno, Experimental colitis alters visceromotor response to colorectal distension in awake rats, Dig. Dis. Sci, vol.39, pp.1239-1248, 1994.

A. Mortha, A. Chudnovskiy, D. Hashimoto, M. Bogunovic, S. P. Spencer et al., Microbiota-dependent crosstalk between macrophages and ILC3 promotes intestinal homeostasis, Science, vol.343, p.1249288, 2014.
DOI : 10.1126/science.1249288

URL : http://europepmc.org/articles/pmc4291125?pdf=render

J. Motta, L. Magne, D. Descamps, C. Rolland, C. Squarzoni-dale et al., Modifying the protease, antiprotease pattern by elafin overexpression protects mice from colitis, Gastroenterology, vol.140, pp.1272-1282, 2011.
DOI : 10.1053/j.gastro.2010.12.050

URL : https://hal-pasteur.archives-ouvertes.fr/pasteur-00552947/file/Motta_et_al_Oct._2010_last_unmarked.pdf

J. Motta, L. G. Bermúdez-humarán, C. Deraison, L. Martin, C. Rolland et al., Food-grade bacteria expressing elafin protect against inflammation and restore colon homeostasis, Sci. Transl, 2012.
DOI : 10.1126/scitranslmed.3004212

URL : https://hal.archives-ouvertes.fr/hal-01204261

W. A. Muller, Getting leukocytes to the site of inflammation, Vet. Pathol, vol.50, pp.7-22, 2013.

T. B. Murdoch, W. Xu, J. M. Stempak, C. Landers, S. R. Targan et al., Pattern recognition receptor and autophagy gene variants are associated with development of antimicrobial antibodies in Crohn's disease, Inflamm. Bowel Dis, vol.18, pp.1743-1748, 2012.

T. G. Murrell and D. J. Deller, Intestinal motility in man: the effect of bradykinin on the motility of the distal colon, Am. J. Dig. Dis, vol.12, pp.568-576, 1967.

W. S. Nanayakkara, P. M. Skidmore, L. O'brien, T. J. Wilkinson, and R. B. Gearry, Efficacy of the low FODMAP diet for treating irritable bowel syndrome: the evidence to date, Clin. Exp. Gastroenterol, vol.9, p.131, 2016.

F. Narducci, W. J. Snape, W. M. Battle, R. L. London, and S. Cohen, Increased colonic motility during exposure to a stressful situation, Dig. Dis. Sci, vol.30, pp.40-44, 1985.
DOI : 10.1007/bf01318369

C. Nathan, Points of control in inflammation, Nature, vol.420, pp.846-852, 2002.

D. R. Neill, S. H. Wong, A. Bellosi, R. J. Flynn, M. Daly et al., Nuocytes represent a new innate effector leukocyte that mediates type-2 immunity, Nature, vol.464, pp.1367-1370, 2010.
DOI : 10.1038/nature08900

URL : http://europepmc.org/articles/pmc2862165?pdf=render

M. F. Neurath, Cytokines in inflammatory bowel disease, Nat. Rev. Immunol, vol.14, pp.329-342, 2014.

R. D. Newberry and R. G. Lorenz, Organizing a mucosal defense, Immunol. Rev, vol.206, pp.6-21, 2005.
DOI : 10.1111/j.0105-2896.2005.00282.x

G. Nicolas, M. Bennoun, I. Devaux, C. Beaumont, B. Grandchamp et al., Lack of hepcidin gene expression and severe tissue iron overload in upstream stimulatory factor 2 (USF2) knockout mice, Proc. Natl. Acad. Sci. U. S. A, vol.98, pp.8780-8785, 2001.
URL : https://hal.archives-ouvertes.fr/inserm-00331349

A. M. Niec, B. Frankum, and N. J. Talley, Are adverse food reactions linked to irritable bowel syndrome?, Am. J. Gastroenterol, vol.93, pp.2184-2190, 1998.
DOI : 10.1111/j.1572-0241.1998.00531.x

O. H. Nielsen, B. Vainer, and J. Rask-madsen, Review article: the treatment of inflammatory bowel disease with 6-mercaptopurine or azathioprine, Aliment. Pharmacol. Ther, vol.15, pp.1699-1708, 2001.

J. H. Niess, S. Brand, X. Gu, L. Landsman, S. Jung et al., CX3CR1-mediated dendritic cell access to the intestinal lumen and bacterial clearance, Science, vol.307, pp.254-258, 2005.
DOI : 10.1126/science.1102901

G. Nieto-alamilla, R. Márquez-gómez, A. García-gálvez, G. Morales-figueroa, and J. Arias-montaño, The Histamine H3 Receptor: Structure, Pharmacology, and Function, vol.90, pp.649-673, 2016.
DOI : 10.1124/mol.116.104752

URL : http://molpharm.aspetjournals.org/content/90/5/649.full.pdf

E. Noguchi, Y. Homma, X. Kang, M. G. Netea, M. et al., A Crohn's diseaseassociated NOD2 mutation suppresses transcription of human IL10 by inhibiting activity of the nuclear ribonucleoprotein hnRNP-A1, Nat. Immunol, vol.10, pp.471-479, 2009.

T. T. Nostrant, N. B. Kumar, and H. D. Appelman, Histopathology differentiates acute self-limited colitis from ulcerative colitis, Gastroenterology, vol.92, pp.318-328, 1987.
DOI : 10.1016/0016-5085(87)90124-7

O. Nufer, M. Corbett, and A. Walz, Amino-terminal processing of chemokine ENA-78 regulates biological activity, Biochemistry (Mosc.), vol.38, pp.636-642, 1999.
DOI : 10.1021/bi981294s

S. Nystedt, K. Emilsson, C. Wahlestedt, and J. Sundelin, Molecular cloning of a potential proteinase activated receptor, Proc. Natl. Acad. Sci. U. S. A, vol.91, pp.9208-9212, 1994.

S. Nystedt, K. Emilsson, A. K. Larsson, B. Strömbeck, and J. Sundelin, Molecular cloning and functional expression of the gene encoding the human proteinase-activated receptor 2, Eur. J. Biochem, vol.232, pp.84-89, 1995.

N. Obermajer, B. Doljak, P. Jamnik, U. P. Fonovi?, and J. Kos, Cathepsin X cleaves the C-terminal dipeptide of alpha-and gamma-enolase and impairs survival and neuritogenesis of neuronal cells, Int. J. Biochem. Cell Biol, vol.41, pp.1685-1696, 2009.

Y. Ogura, D. K. Bonen, N. Inohara, D. L. Nicolae, F. F. Chen et al., A frameshift mutation in NOD2 associated with susceptibility to Crohn's disease, Nature, vol.411, pp.603-606, 2001.

A. M. O'hara and F. Shanahan, The gut flora as a forgotten organ, EMBO Rep, vol.7, p.688, 2006.

L. Öhman, S. Isaksson, A. Lundgren, M. Simrén, and H. Sjövall, A Controlled Study of Colonic Immune Activity and ?7+ Blood T Lymphocytes in Patients With Irritable Bowel Syndrome, Clin. Gastroenterol. Hepatol, vol.3, pp.980-986, 2005.

I. Okayasu, S. Hatakeyama, M. Yamada, T. Ohkusa, Y. Inagaki et al., A novel method in the induction of reliable experimental acute and chronic ulcerative colitis in mice, Gastroenterology, vol.98, pp.694-702, 1990.

S. Oliva, G. Di-nardo, F. Ferrari, S. Mallardo, P. Rossi et al., Randomised clinical trial: the effectiveness of Lactobacillus reuteri ATCC 55730 rectal enema in children with active distal ulcerative colitis, Aliment. Pharmacol. Ther, vol.35, pp.327-334, 2012.

S. M. O'mahony, M. Tramullas, P. Fitzgerald, C. , and J. F. , Rodent models of colorectal distension, Curr. Protoc. Neurosci. Chapter, issue.9, p.40, 2012.

D. K. Ong, S. B. Mitchell, J. S. Barrett, S. J. Shepherd, P. M. Irving et al., Manipulation of dietary short chain carbohydrates alters the pattern of gas production and genesis of symptoms in irritable bowel syndrome, J. Gastroenterol. Hepatol, vol.25, pp.1366-1373, 2010.

R. Oren, N. Arber, S. Odes, M. Moshkowitz, D. Keter et al., Methotrexate in chronic active ulcerative colitis: a double-blind, randomized, Israeli multicenter trial, Gastroenterology, vol.110, pp.1416-1421, 1996.

V. S. Ossovskaya and N. W. Bunnett, Protease-activated receptors: contribution to physiology and disease, Physiol. Rev, vol.84, pp.579-621, 2004.

H. Østgaard, T. Hausken, D. Gundersen, and M. Salhy, Diet and effects of diet management on quality of life and symptoms in patients with irritable bowel syndrome, Mol. Med. Rep, vol.5, pp.1382-1390, 2012.

O. Pabst, V. Cerovic, and M. Hornef, Secretory IgA in the Coordination of Establishment and Maintenance of the Microbiota, Trends Immunol, vol.37, pp.287-296, 2016.

M. Pallaoro, M. S. Fejzo, L. Shayesteh, J. L. Blount, and G. H. Caughey, Characterization of genes encoding known and novel human mast cell tryptases on chromosome 16p13.3, J. Biol. Chem, vol.274, pp.3355-3362, 1999.

R. Panaccione, J. G. Ferraz, B. , and P. , Advances in medical therapy of inflammatory bowel disease, Curr. Opin. Pharmacol, vol.5, pp.566-572, 2005.

M. Pathak, S. S. Wong, I. Dreveny, and J. Emsley, Structure of plasma and tissue kallikreins, Thromb. Haemost, vol.110, pp.423-433, 2013.

Z. Pei, E. J. Bini, L. Yang, M. Zhou, F. Francois et al., Bacterial biota in the human distal esophagus, Proc. Natl. Acad. Sci. U. S. A, vol.101, pp.4250-4255, 2004.

W. F. Pendergraft, E. H. Rudolph, R. J. Falk, J. E. Jahn, M. Grimmler et al., Proteinase 3 sidesteps caspases and cleaves p21(Waf1/Cip1/Sdi1) to induce endothelial cell apoptosis, Kidney Int, vol.65, pp.75-84, 2004.

D. H. Perlmutter, G. I. Glover, M. Rivetna, C. S. Schasteen, F. et al., Identification of a serpin-enzyme complex receptor on human hepatoma cells and human monocytes, Proc. Natl. Acad. Sci. U. S. A, vol.87, p.3753, 1990.

S. L. Peters, J. G. Muir, and P. R. Gibson, Review article: gut-directed hypnotherapy in the management of irritable bowel syndrome and inflammatory bowel disease, 2015.

, Aliment. Pharmacol. Ther, vol.41, pp.1104-1115

L. W. Peterson and D. Artis, Intestinal epithelial cells: regulators of barrier function and immune homeostasis, Nat. Rev. Immunol, vol.14, pp.141-153, 2014.

L. Peyrin-biroulet, P. Deltenre, N. De-suray, J. Branche, W. J. Sandborn et al., Efficacy and safety of tumor necrosis factor antagonists in Crohn's disease: meta-analysis of placebo-controlled trials, Clin. Gastroenterol. Hepatol. Off. Clin. Pract. J. Am. Gastroenterol. Assoc, vol.6, pp.644-653, 2008.

R. Pfundt, F. Van-ruissen, I. M. Van-vlijmen-willems, H. A. Alkemade, P. L. Zeeuwen et al., Constitutive and inducible expression of SKALP/elafin provides anti-elastase defense in human epithelia, J. Clin. Invest, vol.98, pp.1389-1399, 1996.

C. T. Pham, Neutrophil serine proteases: specific regulators of inflammation, Nat. Rev. Immunol, vol.6, pp.541-550, 2006.

T. Piche, Tight junctions and IBS-the link between epithelial permeability, lowgrade inflammation, and symptom generation?, Neurogastroenterol. Motil, vol.26, pp.296-302, 2014.

J. M. Pickard and A. V. Chervonsky, Sampling of the intestinal microbiota by epithelial M cells, Curr. Gastroenterol. Rep, vol.12, pp.331-339, 2010.

M. Pimentel, S. Chatterjee, C. Chang, K. Low, Y. Song et al., A new rat model links two contemporary theories in irritable bowel syndrome, Dig. Dis. Sci, vol.53, pp.982-989, 2008.

M. Pimentel, L. Hwang, G. Y. Melmed, K. Low, E. Vasiliauskas et al., New Clinical Method for Distinguishing D-IBS from Other Gastrointestinal Conditions Causing Diarrhea: The LA/IBS Diagnostic Strategy, Dig. Dis. Sci, vol.55, pp.145-149, 2010.

A. C. Piscaglia, Intestinal stem cells and celiac disease, World J. Stem Cells, vol.6, p.213, 2014.

A. M. Platt, C. C. Bain, Y. Bordon, D. P. Sester, and A. M. Mowat, An independent subset of TLR expressing CCR2-dependent macrophages promotes colonic inflammation, J. Immunol. Baltim. Md, vol.184, pp.6843-6854, 1950.

I. Posserud, P. Stotzer, E. S. Bjornsson, H. Abrahamsson, and M. Simren, , 2007.

, Small intestinal bacterial overgrowth in patients with irritable bowel syndrome, Gut, vol.56, pp.802-808

T. L. Powley and R. J. Phillips, Musings on the wanderer: what's new in our understanding of vago-vagal reflexes? I. Morphology and topography of vagal afferents innervating the GI tract, Am. J. Physiol. Gastrointest. Liver Physiol, vol.283, pp.1217-1225, 2002.

C. Prantera, M. L. Scribano, G. Falasco, A. Andreoli, and C. Luzi, Ineffectiveness of probiotics in preventing recurrence after curative resection for Crohn's disease: a randomised controlled trial with Lactobacillus GG, Gut, vol.51, pp.405-409, 2002.

S. Prasad, R. Mingrino, K. Kaukinen, K. L. Hayes, R. M. Powell et al., Inflammatory processes have differential effects on claudins 2, 3 and 4 in colonic epithelial cells, Lab. Investig. J. Tech. Methods Pathol, vol.85, pp.1139-1162, 2005.

M. Pruteanu, N. P. Hyland, D. J. Clarke, B. Kiely, and F. Shanahan, Degradation of the extracellular matrix components by bacterial-derived metalloproteases: implications for inflammatory bowel diseases, Inflamm. Bowel Dis, vol.17, pp.1189-1200, 2011.

A. Psichas, F. Reimann, and F. M. Gribble, Gut chemosensing mechanisms, J. Clin. Invest, vol.125, pp.908-917, 2015.

H. Qin, J. C. Wu, X. Tong, J. J. Sung, H. Xu et al., Systematic review of animal models of post-infectious/post-inflammatory irritable bowel syndrome, J. Gastroenterol, vol.46, pp.164-174, 2011.

E. Quévrain, M. A. Maubert, C. Michon, F. Chain, R. Marquant et al., Identification of an antiinflammatory protein from Faecalibacterium prausnitzii, a commensal bacterium deficient in Crohn's disease, Gut, vol.65, pp.415-425, 2016.

J. F. Quinton, B. Sendid, D. Reumaux, P. Duthilleul, A. Cortot et al., Anti-Saccharomyces cerevisiae mannan antibodies combined with antineutrophil cytoplasmic autoantibodies in inflammatory bowel disease: prevalence and diagnostic role, Gut, vol.42, pp.788-791, 1998.

M. Raithel, S. Winterkamp, A. Pacurar, P. Ulrich, J. Hochberger et al., Release of mast cell tryptase from human colorectal mucosa in inflammatory bowel disease, Scand. J. Gastroenterol, vol.36, pp.174-179, 2001.

M. Rajili?-stojanovi?, E. Biagi, H. G. Heilig, K. Kajander, R. A. Kekkonen et al., Global and Deep Molecular Analysis of Microbiota Signatures in Fecal Samples From Patients With Irritable Bowel Syndrome, Gastroenterology, vol.141, pp.1792-1801, 2011.

M. Rajili?-stojanovi?, D. M. Jonkers, A. Salonen, K. Hanevik, J. Raes et al., Intestinal Microbiota And Diet in IBS: Causes, Consequences, or Epiphenomena?, Am. J. Gastroenterol, vol.110, pp.278-287, 2015.

R. Ramachandran, K. Mihara, H. Chung, B. Renaux, C. S. Lau et al., Neutrophil elastase acts as a biased agonist for proteinase-activated receptor-2 (PAR2), J. Biol. Chem, vol.286, pp.24638-24648, 2011.

G. Ramelli, S. Fuertes, S. Narayan, N. Busso, H. Acha-orbea et al., Proteaseactivated receptor 2 signalling promotes dendritic cell antigen transport and T-cell activation in vivo, Immunology, vol.129, pp.20-27, 2010.

R. Ransford, .. J. Langman, and M. J. , Sulphasalazine and mesalazine: serious adverse reactions re-evaluated on the basis of suspected adverse reaction reports to the Committee on Safety of Medicines, Gut, vol.51, pp.536-539, 2002.

N. V. Rao, B. C. Marshall, B. H. Gray, and J. R. Hoidal, Interaction of secretory leukocyte protease inhibitor with proteinase-3, Am. J. Respir. Cell Mol. Biol, vol.8, pp.612-616, 1993.

U. B. Rasmussen, V. Vouret-craviari, S. Jallat, Y. Schlesinger, G. Pagès et al., cDNA cloning and expression of a hamster alpha-thrombin receptor coupled to Ca2+ mobilization, FEBS Lett, vol.288, pp.123-128, 1991.

E. M. Ratcliffe, Molecular development of the extrinsic sensory innervation of the gastrointestinal tract, Auton. Neurosci, vol.161, pp.1-5, 2011.

N. D. Rawlings, Peptidase inhibitors in the MEROPS database, Biochimie, vol.92, pp.1463-1483, 2010.

K. K. Reed and R. Wickham, Review of the Gastrointestinal Tract: From Macro to Micro, Semin. Oncol. Nurs, vol.25, pp.3-14, 2009.

D. E. Reed, C. Barajas-lopez, G. Cottrell, S. Velazquez-rocha, O. Dery et al., Mast cell tryptase and proteinase-activated receptor 2 induce hyperexcitability of guinea-pig submucosal neurons, J. Physiol, vol.547, pp.531-542, 2003.

I. Ricciardelli, K. J. Lindley, M. Londei, and S. Quaratino, Anti tumour necrosisalpha therapy increases the number of FOXP3 regulatory T cells in children affected by Crohn's disease, Immunology, vol.125, pp.178-183, 2008.

M. Rimoldi, M. Chieppa, V. Salucci, F. Avogadri, A. Sonzogni et al., Intestinal immune homeostasis is regulated by the crosstalk between epithelial cells and dendritic cells, Nat. Immunol, vol.6, pp.507-514, 2005.

H. Rinderknecht, I. G. Renner, S. B. Abramson, and C. Carmack, Mesotrypsin: a new inhibitor-resistant protease from a zymogen in human pancreatic tissue and fluid, Gastroenterology, vol.86, pp.681-692, 1984.

A. M. Riordan, C. H. Ruxton, and J. O. Hunter, A review of associations between Crohn's disease and consumption of sugars, Eur. J. Clin. Nutr, vol.52, pp.229-238, 1998.

M. A. Rivas, M. Beaudoin, A. Gardet, C. Stevens, Y. Sharma et al., Deep resequencing of GWAS loci identifies independent rare variants associated with inflammatory bowel disease, Nat. Genet, vol.43, pp.1066-1073, 2011.

X. Roblin and B. Bonaz, Osteoporosis and inflammatory bowel disease, Am. J. Gastroenterol, vol.102, 0209.
URL : https://hal.archives-ouvertes.fr/inserm-00417770

G. Roda, A. Sartini, E. Zambon, A. Calafiore, M. Marocchi et al., Intestinal epithelial cells in inflammatory bowel diseases, World J. Gastroenterol. WJG, vol.16, pp.4264-4271, 2010.

V. E. Rolfe, P. J. Fortun, C. J. Hawkey, and F. Bath-hextall, Probiotics for maintenance of remission in Crohn's disease, Cochrane Database Syst. Rev. CD004826, 2006.

C. Rolland-fourcade, A. Denadai-souza, C. Cirillo, C. Lopez, J. O. Jaramillo et al., Epithelial expression and function of trypsin-3 in irritable bowel syndrome, 2017.

M. R. Rosen, P. R. Brink, I. S. Cohen, R. , and R. B. , Genes, stem cells and biological pacemakers, Cardiovasc. Res, vol.64, pp.12-23, 2004.

R. Rosenthal, S. Milatz, S. M. Krug, B. Oelrich, J. Schulzke et al., Claudin-2, a component of the tight junction, forms a paracellular water channel, J. Cell Sci, vol.123, pp.1913-1921, 2010.

A. Rot and U. H. Von-andrian, Chemokines in innate and adaptive host defense: basic chemokinese grammar for immune cells, Annu. Rev. Immunol, vol.22, pp.891-928, 2004.

J. L. Round, S. M. Lee, J. Li, G. Tran, B. Jabri et al., , 2011.

, The Toll-like receptor 2 pathway establishes colonization by a commensal of the human microbiota, Science, vol.332, pp.974-977

F. Roviezzo, M. Bucci, V. Brancaleone, A. Di-lorenzo, P. Geppetti et al., Proteinase-activated receptor-2 mediates arterial vasodilation in diabetes, Arterioscler. Thromb. Vasc. Biol, vol.25, pp.2349-2354, 2005.

L. Rust, E. C. Pesci, and B. H. Iglewski, Analysis of the Pseudomonas aeruginosa elastase (lasB) regulatory region, J. Bacteriol, vol.178, pp.1134-1140, 1996.

J. Saboti? and J. Kos, Microbial and fungal protease inhibitors-current and potential applications, Appl. Microbiol. Biotechnol, vol.93, pp.1351-1375, 2012.

M. Sahin-tóth, HUMAN MESOTRYPSIN DEFIES NATURAL TRYPSIN INHIBITORS. FROM PASSIVE RESISTANCE TO ACTIVE DESTRUCTION, Protein Pept. Lett, vol.12, pp.457-464, 2005.

Y. A. Saito, G. R. Locke, A. L. Weaver, A. R. Zinsmeister, and N. J. Talley, Diet and functional gastrointestinal disorders: a population-based case-control study, Am. J. Gastroenterol, vol.100, pp.2743-2748, 2005.

M. A. Salameh and E. S. Radisky, Biochemical and structural insights into mesotrypsin: an unusual human trypsin, Int. J. Biochem. Mol. Biol, vol.4, pp.129-139, 2013.

J. M. Sallenave, Antimicrobial activity of antiproteinases, Biochem. Soc. Trans, vol.30, pp.111-115, 2002.

J. Sallenave, Secretory leukocyte protease inhibitor and elafin/trappin-2: versatile mucosal antimicrobials and regulators of immunity, Am. J. Respir. Cell Mol. Biol, vol.42, pp.635-643, 2010.

J. Sallenave, Secretory leukocyte protease inhibitor and elafin/trappin-2: versatile mucosal antimicrobials and regulators of immunity, Am. J. Respir. Cell Mol. Biol, vol.42, pp.635-643, 2010.

P. Salmon, K. Skaife, and J. Rhodes, Abuse, dissociation, and somatization in irritable bowel syndrome: towards an explanatory model, J. Behav. Med, vol.26, pp.1-18, 2003.

B. S. Samuel, A. Shaito, T. Motoike, F. E. Rey, F. Backhed et al., Effects of the gut microbiota on host adiposity are modulated by the short-chain fatty-acid binding G protein-coupled receptor, Gpr41. Proc. Natl. Acad. Sci. U. S. A, vol.105, pp.16767-16772, 2008.

W. Sandborn, L. Sutherland, D. Pearson, G. May, R. Modigliani et al., , 2000.

, Azathioprine or 6-mercaptopurine for inducing remission of Crohn's disease, Cochrane Database Syst. Rev. CD000545

W. J. Sandborn, P. Rutgeerts, R. Enns, S. B. Hanauer, J. Colombel et al., Adalimumab induction therapy for Crohn disease previously treated with infliximab: a randomized trial, Ann. Intern. Med, vol.146, pp.829-838, 2007.

K. Sasaki, M. Iizuka, S. Konno, K. Shindo, A. Sato et al., , 2005.

, Ecabet sodium prevents the delay of wound repair in intestinal epithelial cells induced by hydrogen peroxide, J. Gastroenterol, vol.40, pp.474-482

T. Sato, R. G. Vries, H. J. Snippert, M. Van-de-wetering, N. Barker et al., Single Lgr5 stem cells build crypt-villus structures in vitro without a mesenchymal niche, Nature, vol.459, pp.262-265, 2009.

T. C. Savidge, P. Newman, C. Pothoulakis, A. Ruhl, M. Neunlist et al., Enteric glia regulate intestinal barrier function and inflammation via release of S-nitrosoglutathione, Gastroenterology, vol.132, pp.1344-1358, 2007.

S. Sawa, M. Lochner, N. Satoh-takayama, S. Dulauroy, M. Bérard et al., ROR?t+ innate lymphoid cells regulate intestinal homeostasis by integrating negative signals from the symbiotic microbiota, Nat. Immunol, vol.12, pp.320-326, 2011.

F. Scheiffele and I. J. Fuss, Induction of TNBS colitis in mice, Curr. Protoc. Immunol. Chapter, vol.15, 2002.

M. Schemann, Control of gastrointestinal motility by the "gut brain"-the enteric nervous system, J. Pediatr. Gastroenterol. Nutr, vol.41, issue.1, pp.4-6, 2005.

A. M. Schoepfer, T. Schaffer, B. Seibold-schmid, S. Müller, and F. Seibold, , 2008.

, Antibodies to flagellin indicate reactivity to bacterial antigens in IBS patients, Neurogastroenterol. Motil, vol.20, pp.1110-1118

K. S. Schulze, The imaging and modelling of the physical processes involved in digestion and absorption, Acta Physiol, vol.213, pp.394-405, 2015.

J. Schulzke, C. Bojarski, S. Zeissig, F. Heller, A. H. Gitter et al., Disrupted barrier function through epithelial cell apoptosis, Ann. N. Y. Acad. Sci, vol.1072, pp.288-299, 2006.

M. Schwab, E. Schaeffeler, C. Marx, M. F. Fromm, B. Kaskas et al., Association between the C3435T MDR1 gene polymorphism and susceptibility for ulcerative colitis, Gastroenterology, vol.124, pp.26-33, 2003.

D. H. Scoville, T. Sato, X. C. He, L. , and L. , Current view: intestinal stem cells and signaling, Gastroenterology, vol.134, pp.849-864, 2008.

C. L. Scudamore, M. A. Jepson, B. H. Hirst, and H. R. Miller, The rat mucosal mast cell chymase, RMCP-II, alters epithelial cell monolayer permeability in association with altered distribution of the tight junction proteins ZO-1 and occludin, Eur. J. Cell Biol, vol.75, pp.321-330, 1998.

I. Sekirov, S. L. Russell, L. C. Antunes, and B. B. Finlay, Gut microbiota in health and disease, Physiol. Rev, vol.90, pp.859-904, 2010.

J. N. Sengupta, X. Su, and G. F. Gebhart, Kappa, but not mu or delta, opioids attenuate responses to distention of afferent fibers innervating the rat colon, Gastroenterology, vol.111, pp.968-980, 1996.

J. N. Sengupta, A. Mickle, P. Kannampalli, R. Spruell, J. Mcrorie et al., Visceral analgesic effect of 5-HT(4) receptor agonist in rats involves the rostroventral medulla (RVM), vol.79, pp.345-358, 2014.

C. N. Serhan, N. Chiang, and T. E. Van-dyke, Resolving inflammation: dual antiinflammatory and pro-resolution lipid mediators, Nat. Rev. Immunol, vol.8, pp.349-361, 2008.

B. Shahbazkhani, A. Sadeghi, R. Malekzadeh, F. Khatavi, M. Etemadi et al., Non-Celiac Gluten Sensitivity Has Narrowed the Spectrum of Irritable Bowel Syndrome: A Double-Blind Randomized PlaceboControlled Trial, vol.7, pp.4542-4554, 2015.

L. Shaw and O. Wiedow, Therapeutic potential of human elafin, Biochem. Soc. Trans, vol.39, pp.1450-1454, 2011.

S. J. Shepherd, F. C. Parker, J. G. Muir, and P. R. Gibson, Dietary Triggers of Abdominal Symptoms in Patients With Irritable Bowel Syndrome: Randomized PlaceboControlled Evidence, Clin. Gastroenterol. Hepatol, vol.6, pp.765-771, 2008.

S. J. Shepherd, F. C. Parker, J. G. Muir, and P. R. Gibson, Dietary triggers of abdominal symptoms in patients with irritable bowel syndrome: randomized placebocontrolled evidence, Clin. Gastroenterol. Hepatol. Off. Clin. Pract. J. Am. Gastroenterol. Assoc, vol.6, pp.765-771, 2008.

B. S. Sheridan and L. Lefrançois, Intraepithelial Lymphocytes: To Serve and Protect, Curr. Gastroenterol. Rep, vol.12, p.513, 2010.

K. Shindo, M. Iizuka, K. Sasaki, S. Konno, H. Itou et al., , 2006.

, Sucralfate prevents the delay of wound repair in intestinal epithelial cells by hydrogen peroxide through NF-kappaB pathway, J. Gastroenterol, vol.41, pp.450-461

V. Shpacovitch, M. Feld, M. D. Hollenberg, T. A. Luger, and M. Steinhoff, Role of protease-activated receptors in inflammatory responses, innate and adaptive immunity, J. Leukoc. Biol, vol.83, pp.1309-1322, 2008.

N. Shulzhenko, A. Morgun, W. Hsiao, M. Battle, M. Yao et al., Crosstalk between B lymphocytes, microbiota and the intestinal epithelium governs immunity versus metabolism in the gut, Nat. Med, vol.17, pp.1585-1593, 2011.

C. A. Siegel and R. P. Macdermott, Is chronic pain an extraintestinal manifestation of IBD?, Inflamm. Bowel Dis, vol.15, pp.769-771, 2009.

K. J. Simpson, L. M. Selfors, J. Bui, A. Reynolds, D. Leake et al., Identification of genes that regulate epithelial cell migration using an siRNA screening approach, Nat. Cell Biol, vol.10, pp.1027-1038, 2008.

V. Singh, J. Yang, T. Chen, N. C. Zachos, O. Kovbasnjuk et al., Translating molecular physiology of intestinal transport into pharmacologic treatment of diarrhea: stimulation of Na+ absorption, Clin. Gastroenterol. Hepatol. Off. Clin. Pract. J. Am. Gastroenterol. Assoc, vol.12, pp.27-31, 2014.

H. Sjövall, H. Abrahamsson, G. Westlander, R. Gillberg, S. Redfors et al., Intestinal fluid and electrolyte transport in man during reduced circulating blood volume, Gut, vol.27, pp.913-918, 1986.

J. L. Smith and D. Bayles, Postinfectious irritable bowel syndrome: a long-term consequence of bacterial gastroenteritis, J. Food Prot, vol.70, pp.1762-1769, 2007.

P. M. Smith, M. R. Howitt, N. Panikov, M. Michaud, C. A. Gallini et al., The microbial metabolites, short-chain fatty acids, regulate colonic Treg cell homeostasis, Science, vol.341, pp.569-573, 2013.

W. J. Snape, G. M. Carlson, and S. Cohen, Colonic myoelectric activity in the irritable bowel syndrome, Gastroenterology, vol.70, pp.326-330, 1976.

W. D. Snider and S. B. Mcmahon, Tackling pain at the source: new ideas about nociceptors, Neuron, vol.20, pp.629-632, 1998.

J. D. Söderholm, P. Yang, P. Ceponis, A. Vohra, R. Riddell et al., Chronic stress induces mast cell-dependent bacterial adherence and initiates mucosal inflammation in rat intestine, Gastroenterology, vol.123, pp.1099-1108, 2002.

U. J. Soh, M. R. Dores, B. Chen, and J. Trejo, Signal transduction by proteaseactivated receptors, Br. J. Pharmacol, vol.160, pp.191-203, 2010.

H. Sokol, B. Pigneur, L. Watterlot, O. Lakhdari, L. G. Bermúdez-humarán et al., Faecalibacterium prausnitzii is an anti-inflammatory commensal bacterium identified by gut microbiota analysis of Crohn disease patients, Proc. Natl. Acad. Sci. U. S. A, vol.105, pp.16731-16736, 2008.
URL : https://hal.archives-ouvertes.fr/hal-00652961

H. S. Souza, C. J. Tortori, M. T. Castelo-branco, A. T. Carvalho, V. S. Margallo et al., Apoptosis in the intestinal mucosa of patients with inflammatory bowel disease: evidence of altered expression of FasL and perforin cytotoxic pathways, Int. J. Colorectal Dis, vol.20, pp.277-286, 2005.

H. S. De-souza and C. Fiocchi, Immunopathogenesis of IBD: current state of the art, Nat. Rev. Gastroenterol. Hepatol, vol.13, pp.13-27, 2016.

J. Spencer, P. G. Isaacson, T. T. Macdonald, A. J. Thomas, and J. A. Walker-smith, , 1991.

, Gamma/delta T cells and the diagnosis of coeliac disease, Clin. Exp. Immunol, vol.85, pp.109-113

R. Spiller, Role of motility in chronic diarrhoea, Neurogastroenterol. Motil. Off. J. Eur. Gastrointest. Motil. Soc, vol.18, pp.1045-1055, 2006.

R. C. Spiller, Postinfectious irritable bowel syndrome, Gastroenterology, vol.124, pp.1662-1671, 2003.

R. Spiller and K. Garsed, Postinfectious irritable bowel syndrome, Gastroenterology, vol.136, pp.1979-1988, 2009.

R. C. Spiller, D. Jenkins, J. P. Thornley, J. M. Hebden, T. Wright et al., Increased rectal mucosal enteroendocrine cells, T lymphocytes, and increased gut permeability following acute Campylobacter enteritis and in post-dysenteric irritable bowel syndrome, Gut, vol.47, pp.804-811, 2000.
DOI : 10.1136/gut.47.6.804

URL : http://europepmc.org/articles/pmc1728147?pdf=render

A. Stadnicki, R. A. Dela-cadena, R. B. Sartor, D. Bender, C. A. Kettner et al., Selective plasma kallikrein inhibitor attenuates acute intestinal inflammation in Lewis rat, Dig. Dis. Sci, vol.41, pp.912-920, 1996.
DOI : 10.1007/bf02091530

A. Stadnicki, U. Mazurek, D. Plewka, and T. Wilczok, Intestinal tissue kallikreinkallistatin profile in inflammatory bowel disease, Int. Immunopharmacol, vol.3, pp.939-944, 2003.

T. S. Stappenbeck, L. V. Hooper, G. , and J. I. , Developmental regulation of intestinal angiogenesis by indigenous microbes via Paneth cells, Proc. Natl. Acad. Sci. U. S. A, vol.99, pp.15451-15455, 2002.

C. Stasi, M. Bellini, G. Bassotti, C. Blandizzi, and S. Milani, Serotonin receptors and their role in the pathophysiology and therapy of irritable bowel syndrome, Tech. Coloproctology, vol.18, pp.613-621, 2014.

R. Staud, Cytokine and immune system abnormalities in fibromyalgia and other central sensitivity syndromes, Curr. Rheumatol. Rev, vol.11, pp.109-115, 2015.
DOI : 10.2174/1573397111666150619094819

H. Steed, G. T. Macfarlane, K. L. Blackett, B. Bahrami, N. Reynolds et al., Clinical trial: the microbiological and immunological effects of synbiotic consumption-a randomized double-blind placebocontrolled study in active Crohn's disease, Aliment. Pharmacol. Ther, vol.32, pp.872-883, 2010.

L. Steidler, W. Hans, L. Schotte, S. Neirynck, F. Obermeier et al., Treatment of murine colitis by Lactococcus lactis secreting interleukin-10, Science, vol.289, pp.1352-1355, 2000.

K. A. Steinbrecher, E. Harmel-laws, R. Sitcheran, and A. S. Baldwin, Loss of epithelial RelA results in deregulated intestinal proliferative/apoptotic homeostasis and susceptibility to inflammation, J. Immunol. Baltim. Md, vol.180, pp.2588-2599, 1950.

M. Steinhoff, J. Buddenkotte, V. Shpacovitch, A. Rattenholl, C. Moormann et al., Proteinase-Activated Receptors: Transducers of Proteinase-Mediated Signaling in Inflammation and Immune Response, Endocr. Rev, vol.26, pp.1-43, 2005.

R. J. Stoney, R. , and L. M. , Chronic visceral ischemia. An often overlooked cause of abdominal pain, Postgrad. Med, vol.74, pp.111-118, 1983.

D. K. Strickland, S. C. Muratoglu, A. , and T. M. , Serpin-Enzyme Receptors: LDL Receptor-Related Protein 1, Methods Enzymol, vol.499, p.17, 2011.

A. Sturm and A. U. Dignass, Epithelial restitution and wound healing in inflammatory bowel disease, World J. Gastroenterol. WJG, vol.14, pp.348-353, 2008.
DOI : 10.3748/wjg.14.348

URL : https://doi.org/10.3748/wjg.14.348

I. Sukhotnik, K. Khateeb, J. G. Mogilner, H. Helou, M. Lurie et al., Dietary glutamine supplementation prevents mucosal injury and modulates intestinal epithelial restitution following ischemia-reperfusion injury in the rat, Dig. Dis. Sci, vol.52, pp.1497-1504, 2007.

S. Sullivan, P. Alex, T. Dassopoulos, N. C. Zachos, C. Iacobuzio-donahue et al., Downregulation of sodium transporters and NHERF proteins in IBD patients and mouse colitis models: potential contributors to IBD-associated diarrhea, Inflamm. Bowel Dis, vol.15, pp.261-274, 2009.

J. Sun, X. Shen, Y. Li, Z. Guo, W. Zhu et al., Therapeutic Potential to Modify the Mucus Barrier in Inflammatory Bowel Disease, Nutrients, vol.8, 2016.

V. R. Sutton, D. L. Vaux, and J. A. Trapani, Bcl-2 prevents apoptosis induced by perforin and granzyme B, but not that mediated by whole cytotoxic lymphocytes, J. Immunol. Baltim. Md, vol.158, pp.5783-5790, 1950.

T. Suzuki, T. J. Moraes, E. Vachon, H. H. Ginzberg, T. Huang et al., Proteinaseactivated receptor-1 mediates elastase-induced apoptosis of human lung epithelial cells, Am. J. Respir. Cell Mol. Biol, vol.33, pp.231-247, 2005.

A. Swidsinski, V. Loening-baucke, H. Lochs, H. , and L. , Spatial organization of bacterial flora in normal and inflamed intestine: a fluorescence in situ hybridization study in mice, World J. Gastroenterol, vol.11, pp.1131-1140, 2005.

R. Szmola, Z. Kukor, and M. Sahin-tóth, Human Mesotrypsin Is a Unique Digestive Protease Specialized for the Degradation of Trypsin Inhibitors, J. Biol. Chem, vol.278, pp.48580-48589, 2003.

J. Tack, M. Fried, L. A. Houghton, J. Spicak, and G. Fisher, Systematic review: the efficacy of treatments for irritable bowel syndrome-a European perspective, Aliment. Pharmacol. Ther, vol.24, pp.183-205, 2006.

J. Tack, M. Outryve, . Van, G. Beyens, R. Kerstens et al., , 2009.

. Prucalopride, Resolor) in the treatment of severe chronic constipation in patients dissatisfied with laxatives, Gut, vol.58, pp.357-365

C. C. Taggart, S. Cryan, S. Weldon, A. Gibbons, C. M. Greene et al., Secretory leucoprotease inhibitor binds to NF-kappaB binding sites in monocytes and inhibits p65 binding, J. Exp. Med, vol.202, pp.1659-1668, 2005.

T. Wojno, E. D. Artis, and D. , Innate lymphoid cells: balancing immunity, inflammation, and tissue repair in the intestine, Cell Host Microbe, vol.12, pp.445-457, 2012.

L. Thim, F. Madsen, and S. S. Poulsen, Effect of trefoil factors on the viscoelastic properties of mucus gels, Eur. J. Clin. Invest, vol.32, pp.519-527, 2002.

C. M. Thomas and J. Versalovic, Probiotics-host communication: Modulation of signaling pathways in the intestine, Gut Microbes, vol.1, pp.148-163, 2010.

G. A. Thomas, J. Rhodes, and J. Green, Nicotine and gastrointestinal disease, QJM Mon. J. Assoc. Physicians, vol.89, pp.485-488, 1996.

H. Tian, B. Biehs, S. Warming, K. G. Leong, L. Rangell et al., A reserve stem cell population in small intestine renders Lgr5-positive cells dispensable, Nature, vol.478, pp.255-259, 2011.

C. W. Tiffany and R. M. Burch, Bradykinin stimulates tumor necrosis factor and interleukin-1 release from macrophages, FEBS Lett, vol.247, pp.189-192, 1989.

S. L. Tilley, T. M. Coffman, and B. H. Koller, Mixed messages: modulation of inflammation and immune responses by prostaglandins and thromboxanes, J. Clin. Invest, vol.108, pp.15-23, 2001.

D. Tooth, K. Garsed, G. Singh, L. Marciani, C. Lam et al., Characterisation of faecal protease activity in irritable bowel syndrome with diarrhoea: origin and effect of gut transit, Gut, vol.63, pp.753-760, 2014.

L. Torres, S. M. Karam, C. Wendling, M. Chenard, D. Kershenobich et al., Trefoil factor 1 (TFF1/pS2) deficiency activates the unfolded protein response, Mol. Med. Camb. Mass, vol.8, pp.273-282, 2002.

F. Toumi, M. Neunlist, E. Cassagnau, S. Parois, C. L. Laboisse et al., Human submucosal neurones regulate intestinal epithelial cell proliferation: evidence from a novel co-culture model, Neurogastroenterol. Motil. Off. J. Eur. Gastrointest. Motil. Soc, vol.15, pp.239-242, 2003.

J. A. Trapani, Granzymes: a family of lymphocyte granule serine proteases, 2001.

, Genome Biol, vol.2

G. M. Tremblay, J. M. Sallenave, E. Israél-assayag, Y. Cormier, and J. Gauldie, , 1996.

, Elafin/elastase-specific inhibitor in bronchoalveolar lavage of normal subjects and farmer's lung, Am. J. Respir. Crit. Care Med, vol.154, pp.1092-1098

M. Tsunemi, Y. Matsuura, S. Sakakibara, K. , and Y. , Crystal structure of an elastase-specific inhibitor elafin complexed with porcine pancreatic elastase determined at 1.9 A resolution, Biochemistry (Mosc.), vol.35, pp.11570-11576, 1996.

J. R. Turner, Intestinal mucosal barrier function in health and disease, Nat. Rev. Immunol, vol.9, pp.799-809, 2009.

R. Undseth, A. Berstad, N. Kløw, K. Arnljot, K. S. Moi et al., Abnormal accumulation of intestinal fluid following ingestion of an unabsorbable carbohydrate in patients with irritable bowel syndrome: an MRI study, Neurogastroenterol. Motil. Off. J. Eur. Gastrointest. Motil. Soc, vol.26, pp.1686-1693, 2014.

B. Ursing, T. Alm, F. Bárány, I. Bergelin, K. Ganrot-norlin et al., A comparative study of metronidazole and sulfasalazine for active Crohn's disease: the cooperative Crohn's disease study in Sweden, II. Result. Gastroenterology, vol.83, pp.550-562, 1982.

E. Vachon, Y. Bourbonnais, C. D. Bingle, S. J. Rowe, M. F. Janelle et al., Anti-inflammatory effect of pre-elafin in lipopolysaccharide-induced acute lung inflammation, Biol. Chem, vol.383, pp.1249-1256, 2002.

S. Vaishnava, M. Yamamoto, K. M. Severson, K. A. Ruhn, X. Yu et al., The antibacterial lectin RegIIIgamma promotes the spatial segregation of microbiota and host in the intestine, Science, vol.334, pp.255-258, 2011.

V. Valatas, M. Vakas, K. , and G. , The value of experimental models of colitis in predicting efficacy of biological therapies for inflammatory bowel diseases, Am. J. Physiol. Gastrointest. Liver Physiol, vol.305, pp.763-785, 2013.

X. Valencia, G. Stephens, R. Goldbach-mansky, M. Wilson, E. M. Shevach et al., TNF downmodulates the function of human CD4+CD25hi T-regulatory cells, vol.108, pp.253-261, 2006.

S. J. Van-deventer, Immunotherapy of Crohn's disease, Scand. J. Immunol, vol.51, pp.18-22, 2000.

C. M. Van-itallie, J. Holmes, A. Bridges, J. L. Gookin, M. R. Coccaro et al., The density of small tight junction pores varies among cell types and is increased by expression of claudin-2, J. Cell Sci, vol.121, pp.298-305, 2008.

H. Van-spaendonk, H. Ceuleers, L. Witters, E. Patteet, J. Joossens et al., Regulation of intestinal permeability: The role of proteases, World J. Gastroenterol, vol.23, pp.2106-2123, 2017.

R. M. Vejborg, V. Hancock, A. M. Petersen, K. A. Krogfelt, and P. Klemm, , 2011.

, Comparative genomics of Escherichia coli isolated from patients with inflammatory bowel disease, BMC Genomics, vol.12, p.316

C. Veltkamp, M. Anstaett, K. Wahl, S. Möller, S. Gangl et al., Apoptosis of regulatory T lymphocytes is increased in chronic inflammatory bowel disease and reversed by antiTNF? treatment, Gut, vol.60, pp.1345-1353, 2011.

K. Venkova, G. Meerveld, and B. , Long-lasting changes in small intestinal transport following the recovery from Trichinella spiralis infection, Neurogastroenterol. Motil. Off. J. Eur. Gastrointest. Motil. Soc, vol.18, pp.234-242, 2006.

I. Vera, J. , and F. J. , Eluxadoline in the treatment of diarrhea-predominant irritable bowel syndrome. The SEPD perspective, Rev. Espanola Enfermedades Dig. Organo Of. Soc. Espanola Patol. Dig, 2017.

N. Vergnolle, Proteinase-Activated Receptor-2-Activating Peptides Induce Leukocyte Rolling, Adhesion, and Extravasation In Vivo, J. Immunol, vol.163, pp.5064-5069, 1999.

N. Vergnolle, Modulation of visceral pain and inflammation by proteaseactivated receptors, Br. J. Pharmacol, vol.141, pp.1264-1274, 2004.

N. Vergnolle, Protease-activated receptors and inflammatory hyperalgesia, Mem. Inst. Oswaldo Cruz, vol.100, pp.173-176, 2005.

N. Vergnolle, Protease-activated receptors as drug targets in inflammation and pain, Pharmacol. Ther, vol.123, pp.292-309, 2009.

N. Vergnolle, Protease inhibition as new therapeutic strategy for GI diseases, Gut, 2016.

N. Vergnolle, L. Cellars, A. Mencarelli, G. Rizzo, S. Swaminathan et al., A role for proteinaseactivated receptor-1 in inflammatory bowel diseases, J. Clin. Invest, vol.116, 2006.

W. Vermeulen, J. G. De-man, P. A. Pelckmans, D. Winter, and B. Y. , Neuroanatomy of lower gastrointestinal pain disorders, World J. Gastroenterol, vol.20, pp.1005-1020, 2014.

T. Verrier, B. Solhonne, J. Sallenave, and I. Garcia-verdugo, The WAP protein Trappin-2/Elafin: a handyman in the regulation of inflammatory and immune responses, Int. J. Biochem. Cell Biol, vol.44, pp.1377-1380, 2012.

G. D. Victora and M. C. Nussenzweig, Germinal centers, Annu. Rev. Immunol, vol.30, pp.429-457, 2012.

A. Villani, M. Lemire, M. Thabane, A. Belisle, G. Geneau et al., Genetic Risk Factors for PostInfectious Irritable Bowel Syndrome Following a Waterborne Outbreak of Gastroenteritis, Gastroenterology, vol.138, pp.1502-1513, 2010.

J. Visser, J. Rozing, A. Sapone, K. Lammers, and A. Fasano, Tight Junctions, Intestinal Permeability, and Autoimmunity Celiac Disease and Type 1 Diabetes Paradigms, Ann. N. Y. Acad. Sci, vol.1165, p.195, 2009.

E. Vivier, H. Spits, C. , and T. , Interleukin-22-producing innate immune cells: new players in mucosal immunity and tissue repair?, Nat. Rev. Immunol, vol.9, pp.229-234, 2009.
URL : https://hal.archives-ouvertes.fr/hal-00408427

M. Vivinus-nébot, R. Dainese, R. Anty, M. C. Saint-paul, J. L. Nano et al., Combination of allergic factors can worsen diarrheic irritable bowel syndrome: role of barrier defects and mast cells, Am. J. Gastroenterol, vol.107, pp.75-81, 2012.

M. Vivinus-nébot, G. Frin-mathy, H. Bzioueche, R. Dainese, G. Bernard et al., Functional bowel symptoms in quiescent inflammatory bowel diseases: role of epithelial barrier disruption and lowgrade inflammation, Gut, vol.63, pp.744-752, 2014.

C. Vonarbourg, A. Mortha, V. L. Bui, P. P. Hernandez, E. A. Kiss et al., Regulated expression of nuclear receptor ROR?t confers distinct functional fates to NK cell receptor-expressing ROR?t(+) innate lymphocytes, Immunity, vol.33, pp.736-751, 2010.

T. K. Vu, D. T. Hung, V. I. Wheaton, and S. R. Coughlin, Molecular cloning of a functional thrombin receptor reveals a novel proteolytic mechanism of receptor activation, Cell, vol.64, pp.1057-1068, 1991.

C. Wahl, S. Liptay, G. Adler, and R. M. Schmid, Sulfasalazine: a potent and specific inhibitor of nuclear factor kappa B, J. Clin. Invest, vol.101, pp.1163-1174, 1998.

D. Wald, J. Qin, Z. Zhao, Y. Qian, M. Naramura et al., SIGIRR, a negative regulator of Toll-like receptor-interleukin 1 receptor signaling, Nat. Immunol, vol.4, pp.920-927, 2003.

I. Waldhauer and A. Steinle, NK cells and cancer immunosurveillance, Oncogene, vol.27, pp.5932-5943, 2008.

K. L. Wallace, L. Zheng, Y. Kanazawa, and D. Q. Shih, Immunopathology of inflammatory bowel disease, World J. Gastroenterol, vol.20, pp.6-21, 2014.

R. J. Wallace, N. Mckain, K. J. Shingfield, D. , and E. , Isomers of conjugated linoleic acids are synthesized via different mechanisms in ruminal digesta and bacteria, J. Lipid Res, vol.48, pp.2247-2254, 2007.

C. Wang, D. Meynard, L. , and H. Y. , The role of TMPRSS6/matriptase-2 in iron regulation and anemia, Front. Pharmacol, vol.5, p.114, 2014.

Y. Wang, W. Luo, T. Wartmann, W. Halangk, M. Sahin-tóth et al., , 2006.

, Mesotrypsin, a brain trypsin, activates selectively proteinase-activated receptor-1, but not proteinase-activated receptor-2, in rat astrocytes, J. Neurochem, vol.99, pp.759-769

Y. Wang, W. Luo, and G. Reiser, Trypsin and trypsin-like proteases in the brain: Proteolysis and cellular functions, Cell. Mol. Life Sci, vol.65, pp.237-252, 2007.

C. J. Watson, C. J. Hoare, D. R. Garrod, G. L. Carlson, and G. Warhurst, Interferongamma selectively increases epithelial permeability to large molecules by activating different populations of paracellular pores, J. Cell Sci, vol.118, pp.5221-5230, 2005.

C. T. Weaver and R. D. Hatton, Interplay between the TH17 and TReg cell lineages: a (co-)evolutionary perspective, Nat. Rev. Immunol, vol.9, pp.883-889, 2009.

C. R. Weber, S. C. Nalle, M. Tretiakova, D. T. Rubin, and J. R. Turner, Claudin-1 and claudin-2 expression is elevated in inflammatory bowel disease and may contribute to early neoplastic transformation, Lab. Investig. J. Tech. Methods Pathol, vol.88, pp.1110-1120, 2008.

J. Wehkamp, J. Harder, K. Wehkamp, . Wehkamp-von, B. Meissner et al., NF-kappaB-and AP-1-mediated induction of human beta defensin-2 in intestinal epithelial cells by Escherichia coli Nissle 1917: a novel effect of a probiotic bacterium, Infect. Immun, vol.72, pp.5750-5758, 2004.

J. Wehkamp, K. Fellermann, K. R. Herrlinger, C. L. Bevins, and E. F. Stange, Mechanisms of disease: defensins in gastrointestinal diseases, Nat. Clin. Pract. Gastroenterol. Hepatol, vol.2, pp.406-415, 2005.

J. Wehkamp, M. Götz, K. Herrlinger, W. Steurer, and E. F. Stange, Inflammatory Bowel Disease. Dtsch. Arzteblatt Int, vol.113, pp.72-82, 2016.

H. L. Weiner, A. P. Cunha, . Da, F. Quintana, and H. Wu, Oral Tolerance, Immunol. Rev, vol.206, p.232, 2005.

W. E. Whitehead, O. S. Palsson, R. R. Levy, A. D. Feld, M. Turner et al., Comorbidity in Irritable Bowel Syndrome, Am. J. Gastroenterol, vol.102, pp.2767-2776, 2007.

O. Wiedow and U. Meyer-hoffert, Neutrophil serine proteases: potential key regulators of cell signalling during inflammation, J. Intern. Med, vol.257, pp.319-328, 2005.

U. Wiegand, S. Corbach, A. Minn, J. Kang, and B. Müller-hill, Cloning of the cDNA encoding human brain trypsinogen and characterization of its product, Gene, vol.136, pp.167-175, 1993.

E. M. Wilcz-villega, S. Mcclean, and M. A. Sullivan, Mast cell tryptase reduces junctional adhesion molecule-A (JAM-A) expression in intestinal epithelial cells: implications for the mechanisms of barrier dysfunction in irritable bowel syndrome, Am. J. Gastroenterol, vol.108, pp.1140-1151, 2013.

T. S. Wilkinson, K. Dhaliwal, T. W. Hamilton, A. F. Lipka, L. Farrell et al., Trappin-2 promotes early clearance of Pseudomonas aeruginosa through CD14-dependent macrophage activation and neutrophil recruitment, Am. J. Pathol, vol.174, pp.1338-1346, 2009.

A. J. Williams, M. V. Merrick, and M. A. Eastwood, Idiopathic bile acid malabsorption-a review of clinical presentation, diagnosis, and response to treatment, Gut, vol.32, pp.1004-1006, 1991.

E. Wine, J. C. Ossa, S. D. Gray-owen, and P. M. Sherman, Adherent-invasive Escherichia coli, strain LF82 disrupts apical junctional complexes in polarized epithelia, BMC Microbiol, vol.9, p.180, 2009.

S. Wirtz, C. Neufert, B. Weigmann, and M. F. Neurath, Chemically induced mouse models of intestinal inflammation, Nat. Protoc, vol.2, pp.541-546, 2007.

M. M. Wouters, D. Balemans, S. Van-wanrooy, J. Dooley, V. Cibert-goton et al., , 2016.

, Histamine Receptor H1-Mediated Sensitization of TRPV1 Mediates Visceral Hypersensitivity and Symptoms in Patients With Irritable Bowel Syndrome, vol.150, pp.875-887

N. A. Wright, Epithelial stem cell repertoire in the gut: clues to the origin of cell lineages, proliferative units and cancer, Int. J. Exp. Pathol, vol.81, pp.117-143, 2000.

E. M. Wright and D. D. Loo, Coupling between Na+, sugar, and water transport across the intestine, Ann. N. Y. Acad. Sci, vol.915, pp.54-66, 2000.

W. F. Xu, H. Andersen, T. E. Whitmore, S. R. Presnell, D. P. Yee et al., Cloning and characterization of human protease-activated receptor 4, Proc. Natl. Acad. Sci. U. S. A, vol.95, pp.6642-6646, 1998.

N. Yahagi, M. Ichinose, M. Matsushima, Y. Matsubara, K. Miki et al., Complementary DNA cloning and sequencing of rat enteropeptidase and tissue distribution of its mRNA, Biochem. Biophys. Res. Commun, vol.219, pp.806-812, 1996.

M. Yamamoto, M. Kweon, P. D. Rennert, T. Hiroi, K. Fujihashi et al., Role of gut-associated lymphoreticular tissues in antigen-specific intestinal IgA immunity, J. Immunol. Baltim. Md, vol.173, pp.762-769, 1950.

F. Yan, H. Cao, T. L. Cover, M. K. Washington, Y. Shi et al., Colon-specific delivery of a probiotic-derived soluble protein ameliorates intestinal inflammation in mice through an EGFR-dependent mechanism, J. Clin. Invest, vol.121, pp.2242-2253, 2011.

P. Yang, W. J. Tremaine, R. L. Meyer, and U. B. Prakash, Alpha1-antitrypsin deficiency and inflammatory bowel diseases, Mayo Clin. Proc, vol.75, pp.450-455, 2000.

X. Yang, L. Sheng, Y. Guan, W. Qian, and X. Hou, Synaptic plasticity: the new explanation of visceral hypersensitivity in rats with Trichinella spiralis infection?, Dig. Dis. Sci, vol.54, pp.937-946, 2009.

Y. Yiangou, P. Facer, I. P. Chessell, C. Bountra, C. Chan et al., Voltage-gated ion channel Nav1.7 innervation in patients with idiopathic rectal hypersensitivity and paroxysmal extreme pain disorder (familial rectal pain), Neurosci. Lett, vol.427, pp.77-82, 2007.

Q. L. Ying and S. R. Simon, Kinetics of the inhibition of proteinase 3 by elafin, Am. J. Respir. Cell Mol. Biol, vol.24, pp.83-89, 2001.

A. P. Yu, L. A. Cabanilla, E. Q. Wu, P. M. Mulani, and J. Chao, The costs of Crohn's disease in the United States and other Western countries: a systematic review, Curr. Med. Res. Opin, vol.24, pp.319-328, 2008.

C. Yuan, L. Chen, E. J. Meehan, N. Daly, D. J. Craik et al., Structure of catalytic domain of Matriptase in complex with Sunflower trypsin inhibitor, 2011.

, BMC Struct. Biol, vol.11, p.30

C. Zaph, Y. Du, S. A. Saenz, M. G. Nair, J. G. Perrigoue et al., Commensal-dependent expression of IL-25 regulates the IL-23-IL-17 axis in the intestine, J. Exp. Med, vol.205, pp.2191-2198, 2008.

S. Zar, L. Mincher, M. J. Benson, and D. Kumar, Food-specific IgG4 antibodyguided exclusion diet improves symptoms and rectal compliance in irritable bowel syndrome, Scand. J. Gastroenterol, vol.40, pp.800-807, 2005.

S. Zeissig, T. Bergann, A. Fromm, C. Bojarski, F. Heller et al., Altered ENaC expression leads to impaired sodium absorption in the noninflamed intestine in Crohn's disease, Gastroenterology, vol.134, pp.1436-1447, 2008.

T. Zelante, R. G. Iannitti, C. Cunha, A. De-luca, G. Giovannini et al., Tryptophan catabolites from microbiota engage aryl hydrocarbon receptor and balance mucosal reactivity via interleukin-22, Immunity, vol.39, pp.372-385, 2013.

L. H. Zeuthen, L. N. Fink, and H. Frokiaer, Epithelial cells prime the immune response to an array of gut-derived commensals towards a tolerogenic phenotype through distinct actions of thymic stromal lymphopoietin and transforming growth factor-beta, Immunology, vol.123, pp.197-208, 2008.

P. Zezos, G. Papaioannou, N. Nikolaidis, K. Patsiaoura, A. Papageorgiou et al., Low-molecular-weight heparin (enoxaparin) as adjuvant therapy in the treatment of active ulcerative colitis: a randomized, controlled, comparative study, Aliment. Pharmacol. Ther, vol.23, pp.1443-1453, 2006.

R. Zhang, G. , and J. , Proteinase-Activated Receptor-2 Modulates Ve-Cadherin Expression to Affect Human Vascular Endothelial Barrier Function, J. Cell. Biochem, 2017.
DOI : 10.1002/jcb.26123

J. Zhao, L. Dong, H. Shi, Z. Wang, H. Shi et al., The expression of protease-activated receptor 2 and 4 in the colon of irritable bowel syndrome patients, Dig. Dis. Sci, vol.57, pp.58-64, 2012.

J. Zhao, X. Zheng, H. Chu, J. Zhao, Y. Cong et al., A study of the methodological and clinical validity of the combined lactulose hydrogen breath test with scintigraphic oro-cecal transit test for diagnosing small intestinal bacterial overgrowth in IBS patients, Neurogastroenterol. Motil, vol.26, pp.794-802, 2014.

P. Zhao, T. Lieu, N. Barlow, S. Sostegni, S. Haerteis et al., Neutrophil Elastase Activates Protease-activated Receptor-2 (PAR2) and Transient Receptor Potential Vanilloid 4 (TRPV4) to Cause Inflammation and Pain, J. Biol. Chem, vol.290, pp.13875-13887, 2015.
DOI : 10.1074/jbc.m115.642736

URL : http://www.jbc.org/content/290/22/13875.full.pdf

C. Zoja, R. Donadelli, S. Colleoni, M. Figliuzzi, S. Bonazzola et al., Protein overload stimulates RANTES production by proximal tubular cells depending on NF-kappa B activation, Kidney Int, vol.53, pp.1608-1615, 1998.
DOI : 10.1046/j.1523-1755.1998.00905.x

URL : https://doi.org/10.1046/j.1523-1755.1998.00905.x

V. Zoller, A. Laguna, O. Prazeres-da-costa, T. Buch, B. Göke et al., , 2015.

, microbiota transfer (FMT) in a patient with refractory irritable bowel syndrome

, Dtsch. Med. Wochenschr, vol.140, pp.1232-1236, 1946.

A. A. Zyrek, C. Cichon, S. Helms, C. Enders, U. Sonnenborn et al., Molecular mechanisms underlying the probiotic effects of Escherichia coli Nissle 1917 involve ZO-2 and PKCzeta redistribution resulting in tight junction and epithelial barrier repair, Cell. Microbiol, vol.9, pp.804-816, 2007.