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Impact du microbiome intestinal sur la cholestérolémie : concepts et applications

Abstract : The gut microbiota is associated with several host metabolic disorders, such as cholesterolemia. In this context, the gut microbiota could also have beneficial impact through different microbial pathways, including : coprostanol formation, cholesterol entrapment and bile salt hydrolases (BSH). However, many element remain to be elucidated to mechanistic understanding of the gut microbiota influences host cholesterol metabolism. This PhD project has enriched our conceptual knowledge through research based on the three cholesterol microbial metabolisms. To enhance our insight into the microbiome and its host, we have extended this conceptual approach to mathematical models, which is proving to be an effective approach for studying the dynamics and interactions of complex systems. For the first time, we have developed, a human model of cholesterol metabolism including the gut microbiota to investigate the relative impact of host and microbiota pathways. This model demonstrates that these microbial pathways are an important driver of cholesterol regulation. To strengthen these observations, we have identified three new intestinal bacteria with each of these three microbial metabolic pathways and tested their impact in an animal model, the mouse. This application highlights that BSH constitute the most significant lever to regulate cholesterol levels. To further support these experimental data, we established the attractive hypocholesterolemic potential of BSH active-bacteria in a rabbit model, more similar to humans. Oral administration of the bacteria with BSH led to a reduction in hypercholesterolemia and also, its associated disorders (hepatic lesions and development of atherosclerosis). Taken together, this work provides evidence of the potential intervention of the gut bacteria with BSH activity as a probiotic strategy to counteract hypercholesterolemia.
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Submitted on : Tuesday, January 25, 2022 - 5:43:11 PM
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Mélanie Bourgin. Impact du microbiome intestinal sur la cholestérolémie : concepts et applications. Médecine humaine et pathologie. Université Paris-Saclay, 2021. Français. ⟨NNT : 2021UPASB022⟩. ⟨tel-03543111⟩

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