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Etude du dialogue système entéro-endocrinien/microbiote intestinal

Abstract : The human gastrointestinal tract is colonized by approximatively 1014 commensal bacteria which are in contact with the enteroendocrine system and its hormonal mediators. The influence of these eukaryotic factors on the gut microbiota is not very well known. Therefore, in the present work, we investigated the effect of serotonin (5HT), substance P (SP) and epinephrine (Epi) on the growth and virulence of P. fluorescens. The results showed that bacterial growth of P. fluorescens was not mainly affected by these factors. But interestingly, enteroendocrine factors can led to a modulation of bacterial virulence depending on the eukaryotic substances tested and the origin of bacterial strain (clinical or environmental). Epinephrine is involved in interkingdom signaling and activates expression of virulence genes in several Gram negative pathogens bacteria such as Salmonella and Escherichia coli. Thus, in further work, we decided to study the impact of this neurotransmitter on two intestinal bacteria and opportunistic pathogens: P. aeruginosa PAO1 (Gram negative bacteria) and E. faecalis V583 (Gram positive bacteria). We showed that epinephrine can modulate the cytotoxic potential and adhesion of these bacteria on Caco-2/TC7 cells, and the proinflammatory capacity of E. faecalis V583 was also enhanced. The initial biofilm formation was increased in P. aeruginosa PAO1 after epinephrine exposure, as well as bacterial translocation, and the ability of the germ to alter the permeability, and invade Caco-2/TC7 cells. We thus conclude that epinephrine is able to act on both Gram negative and Gram positive bacteria. Our work suggests that P. aeruginosa and E. faecalis could have sensors to epinephrine even if their nature still has to be determinated. Substance P is known to display antimicrobial activity against several germs such as E. coli.. Interestingly, in our study, we could highlight that substance P promotes aggregation of E. faecalis V583, increases the cytotoxic potential and hydrophobicity of this bacteria, and its ability to produce tyramine and lactic acid. Finally, all these observations show that SP enhances virulence in E. faecalis V583. To evaluate the global effect of hormonal imbalances on the composition of intestinal microbiota, caecal contents of activity-Based anorexia (ABA) mice were compared to control and limited food access (LFA) mice. This study showed an increase of the Firmicutes phylum concomitantly with a decrease of Proteobacteria, in ABA and LFA mice. We can suggest that this may be partly explained by the reduction of their diet. However, we also observed that several bacterial genera appeared or disappeared among the gut microbiota of ABA mice, such as for example Psychrobacillus. Taken together, our study demonstrates that intestinal factors may be sensed by the gut microbiota and could probably participate in health and disease. Enteroendocrine factors can modulate bacterial virulence while precisely hormonal imbalances are noticed in pathologies such as Crohn disease or anorexia. This work opens new perspectives for a better understanding of diseases linked to the gut/brain axis.
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Kelly Biaggini. Etude du dialogue système entéro-endocrinien/microbiote intestinal. Interactions cellulaires [q-bio.CB]. Université de Rouen, 2015. Français. ⟨tel-02366432⟩

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