Abstract
The intestinal microbiota of patients with constipated-predominant irritable bowel syndrome (C-IBS) displays chronic dysbiosis. Our aim was to determine whether this microbial imbalance instigates perturbation of the host intestinal mucosal immune response, using a model of human microbiota-associated rats (HMAR) and dextran sulfate sodium (DSS)-induced experimental colitis. The analysis of the microbiota composition revealed a decrease of the relative abundance of Bacteroides, Roseburia-Eubacterium rectale and Bifidobacterium and an increase of Enterobacteriaceae, Desulfovibrio sp., and mainly Akkermansia muciniphila in C-IBS patients compared to healthy individuals. The bacterial diversity of the gut microbiota of healthy individuals or C-IBS patients was maintained in corresponding HMAR. Animals harboring a C-IBS microbiota had reduced DSS colitis with a decreased expression of pro-inflammatory cytokines from innate, Th1, and Th17 responses. The pre-treatment of conventional C57BL/6 mice or HMAR with A. muciniphila, but not with Escherichia coli, prior exposure to DSS also resulted in a reduction of colitis severity, highlighting that the anti-inflammatory effect of the gut microbiota of C-IBS patients is mediated, in part, by A. muciniphila. This work highlights a novel aspect of the crosstalk between the gut microbiota of C-IBS patients and host intestinal homeostasis.
Highlights
Throughout the intestinal tract of Irritable bowel syndrome (IBS) patients compared with healthy volunteers, notably those in the vicinity of visceral neurons[8]
The current study demonstrates that the intestinal microbiota of constipated IBS (C-IBS) patients protects from dextran sulfate sodium salt (DSS)-induced colitis
The essential role of A. muciniphila, which is more prevalent in gut microbiota of these patients than in healthy individuals, in this protective effect was supported by our findings that mice and human microbiota-associated rats (HMAR) pre-treated with this bacteria exhibit reduced histological damages in the colon and reduced tissue mRNA expression of pro-inflammatory mediators of the innate, Th1 and Th17 responses
Summary
Throughout the intestinal tract of IBS patients compared with healthy volunteers, notably those in the vicinity of visceral neurons[8]. While low grade infiltration of T cells has been observed in the lamina propria[16,17] or in the myenteric plexus[18] of IBS patients, numerous studies has found normal or decreased lymphocyte density in the intestinal tissues[19,20] In this context, our aim was to investigate the effect of the human intestinal microbiota of C-IBS patients on the mucosal immune response. Our aim was to investigate the effect of the human intestinal microbiota of C-IBS patients on the mucosal immune response For this purpose, we used HMAR, and demonstrate that the gut microbiota of C-IBS patients protects animals from dextran sulfate sodium salt (DSS)-induced colitis. This protective effect is mediated by the increased abundance of the bacterium Akkermensia muciniphila in the C-IBS microbiota compared to healthy subjects
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