Rôle de l’hème dans la primo-colonisation de Bacteroides thetaiotaomicron dans le tractus digestif

Abstract : The intestinal microbiota comprises the numerous microorganisms colonizing the digestive tract. This flora, and the variations it undergoes are unique and specific to each individual. The microbial balance, which is a determinant of our state of health, develops gradually from birth. In addition to the known roles of the microbiote in digestion, it is now recognized as an important contributor to human metabolism. Among the 10¹³ bacteria inhabiting the human gut, the genus Bacteroides comprises the dominant genus, and is needed to digest complex dietary polysaccharide fibers. This feature, and the resistance to trace oxygen of these Gram-negative anaerobes make them particularly well adapted to the intestinal environment. Remarkably, although heme is a required metabolite for Bacteroides growth, these bacteria are incapable of heme synthesis. Heme, which comprises an iron atom trapped within a porphyrin ring, is a cofactor involved in numerous enzymatic reactions essential to central metabolism. Its bioactivity may also provoke intestinal inflammatory phenomena. We investigated the interactions between the bacterium Bacteroides thetaiotaomicron and environmental heme. We first developed a test to detect nanogram amounts of heme in complex media such as intestinal contents. We then showed that the commensal bacterium Escherichia coli donates heme to B. thetaiotaomicron in vitro. Nevertheless, we found that E. coli is not the major heme source for Bacteroides colonization, as tested in a germfree mouse model. This study led us to conclude that the host must be the major heme donor. We then set up a system to modulate heme availability in the digestive tract by capturing free heme on a hemophore HasA, from Serratia marcescens. We confirmed the HasA system was active in vitro. Preliminary experiments indicate that it 1- reduces levels of intestinal heme, and 2- delays B. thetaiotaomicron colonization. The present work provides tools for better understanding the factors needed for Bacteroides implantation in the gut and underlines the importance of heme in this crucial process of primocolonization. In the longer term, the bacterial heme-capture system may be considered as a means of decreasing free intestinal pools of heme and thereby its pro-inflammatory effect, in chronic inflammatory bowel diseases.
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David Halpern. Rôle de l’hème dans la primo-colonisation de Bacteroides thetaiotaomicron dans le tractus digestif. Microbiologie et Parasitologie. Université Paris-Saclay, 2017. Français. ⟨NNT : 2017SACLS369⟩. ⟨tel-02356788⟩



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