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Composition et dynamique du microbiote vaginal : facteurs associés et rôle dans l’infection par Chlamydia trachomatis

Abstract : Chlamydia trachomatis (CT) is a sexually transmitted bacteria responsible for cervicitis, urethritis, and pelvic inflammatory diseases leading to subsequent tubal infertility and ectopic pregnancies. It is the most frequent sexually transmitted infection worldwide, including in France. Epidemiological data indicate that the incidence rate is increasing despite the implementation of control measures, which motivates the revision of current screening strategies. The vaginal microbiota could play a major role in preventing sexually transmitted infections through ecological competition and metabolites, such as lactic acid production. The vaginal microbiota corresponds to a fine-tuned equilibrium likely to be modified by exposures such as sexual practices, hygiene practices, antibiotics but also presence of pathogens. The overall objective of this thesis is to study the association in this triangle composed of external exposures, vaginal microbiota and CT infection, through the study of the vaginal microbiota composition and dynamics. We aimed at answering these questions: are there biomarkers of CT infection in the vaginal microbiota? Are the vaginal microbiota composition and structure modified by CT infection and antibiotic consumption? What are the exposures associated with perturbations of the vaginal microbiota? To answer these questions, the first step consisted of a state of the art to estimate the association between vaginal microbiota and CT infection in the literature, as well as three other clinically relevant sexually transmitted infections, and to evaluate the role of several factors in the observed heterogeneity between studies. In a second step, we estimated this association using molecular characterization of the vaginal microbiota in two studies in France and in the United States. We showed that Lactobacillus iners-dominated communities (CST III) and Lactobacillus-deprived communities (CST IV) were over-represented among CT-positive women. By studying the vaginal microbiota after azithromycin treatment and CT clearance in the American study, we showed that the vaginal microbiota did not evolve towards an optimal state, suggesting that women may stay at risk of CT reinfections. Finally, in two longitudinal studies using frequent sampling in the United States, we studied exposures associated with incidence and clearance of a CST IV. We showed that when the vaginal microbiota was not dominated by L. iners, menses was the main factor associated with incidence and clearance of a CST IV, while for women whose vaginal microbiota is dominated by L. iners, menses but also lubricant use, douching, ethnic origins, age and condomless vaginal sex were associated with CST IV incidence and/or clearance. Therefore, this thesis allowed on the one hand to confirm the association between Lactobacillus-deprived vaginal microbiota and CT infection using genome sequencing, and on the other hand to single out L. iners from other Lactobacillus spp. and to evaluated the risk associated with CST III. By enabling a better understanding of the natural history of CT and of the vaginal microbiota dynamics, we hope to contribute to improving strategies for the control of CT infection and other STIs. The innovative potential of the project lies in the use of molecular methods, which allows refining of our approach of health management by integrating individual predisposition to sexually transmitted infections, thus paving the way for personalized medicine.
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Jeanne Tamarelle. Composition et dynamique du microbiote vaginal : facteurs associés et rôle dans l’infection par Chlamydia trachomatis. Santé publique et épidémiologie. Université Paris-Saclay, 2019. Français. ⟨NNT : 2019SACLV097⟩. ⟨tel-02614316⟩

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