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Etude des perturbations de l'homéostasie intestinale en cas d'infection par citrobacter rodentium. Conséquences sur le bien-être de l'hôte

Abstract : Irritable bowel syndrome (IBS) is the most common functional gastrointestinal disorder. It is characterized by abdominal pain, whose underlying mechanisms is colonic hypersensitivity (CHS), and is often associated with mood disorders. IBS can occur following bacterial infectious enteritis and is referred as to post-infectious IBS. Nowadays, it is not known why only a subgroup of patients develop this disorder while others recover from the infection. Hence, it is necessary to develop a relevant post-infectious animal model in order to better characterize the pathogenesis of IBS. The mouse model of Citrobacter rodentium infection is widely use to mimic human pathogenic Escherichia coli infection, causative infectious agents in the development of post-infectious IBS. Thus, the aim of this study was to characterize disturbances of intestinal homeostasis associated with CHS and mood disorders development by using the mouse model of C. rodentium infection.Study of C. rodentium-induced comorbidities revealed development of CHS and anxiety-like behavior in post-infectious period. Assessment of colonic parameters indicated the development of long-lasting colonic low-grade inflammation. Assessment of the composition of colonic mucosa-associated microbiota highlighted gut dysbiosis similar to that observed in IBS patients. Interestingly, we found a correlation between relative abundance of Burkholderiales and anxiety-like behavior. Analysis of bacterial metabolites revealed an increase of fecal concentration of acetic acid in infected mice. Finally, we observed improvement of CHS and anxiety-like behavior by inducing interleukin-22 (IL-22) expression in enterocytes, through an inflammation independent mechanism.Thanks to the use of the mouse model of C. rodentium infection, our study allowed to better characterize peripheral mechanisms associated with post-infectious IBS. These results offer the opportunity to develop new therapeutic strategies targeting intestinal microbiota and/or IL-22 signaling pathway for a better care of patients or prevent post-infectious IBS.
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Submitted on : Tuesday, June 30, 2020 - 4:44:39 PM
Last modification on : Tuesday, February 23, 2021 - 1:32:01 PM


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Elodie Baudu. Etude des perturbations de l'homéostasie intestinale en cas d'infection par citrobacter rodentium. Conséquences sur le bien-être de l'hôte. Santé. Université Clermont Auvergne, 2018. Français. ⟨NNT : 2018CLFAS020⟩. ⟨tel-02885439⟩



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