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Inflammatory bowel disease (IBD) is a chronic and relapsing inflammatory disease of the gastrointestinal tract. Although the precise etiology of IBD remains incompletely understood, accumulating evidence suggests that various environmental factors, including dietary nutrients, contribute to its pathogenesis. Dietary nutrients are known to have an impact on host physiology and diseases. The interactions between dietary nutrients and intestinal immunity are complex. Dietary nutrients directly regulate the immuno-modulatory function of gut-resident immune cells. Likewise, dietary nutrients shape the composition of the gut microbiota. Therefore, a well-balanced diet is crucial for good health. In contrast, the relationships among dietary nutrients, host immunity and/or the gut microbiota may be perturbed in the context of IBD. Genetic predispositions and gut dysbiosis may affect the utilization of dietary nutrients. Moreover, the metabolism of nutrients in host cells and the gut microbiota may be altered by intestinal inflammation, thereby increasing or decreasing the demand for certain nutrients necessary for the maintenance of immune and microbial homeostasis. Herein, we review the current knowledge of the role dietary nutrients play in the development and the treatment of IBD, focusing on the interplay among dietary nutrients, the gut microbiota and host immune cells. We also discuss alterations in the nutritional metabolism of the gut microbiota and host cells in IBD that can influence the outcome of nutritional intervention. A better understanding of the diet-host-microbiota interactions may lead to new therapeutic approaches for the treatment of IBD.
Macrophages (Mϕs) are known to be major producers of the anti-inflammatory cytokine interleukin-10 (IL-10) in the intestine, thus playing an important role in maintaining gastrointestinal homeostasis. Mϕs that reside in the small intestine (SI) have been previously shown to be regulated by dietary antigens, while colonic Mϕs are regulated by the microbiota. However, the role which resident Mϕs play in SI homeostasis has not yet been fully elucidated. Here, we show that SI Mϕs regulate the integrity of the epithelial barrier via secretion of IL-10. We used an animal model of non-steroidal anti-inflammatory drug (NSAID)-induced SI epithelial injury to show that IL-10 is mainly produced by MHCII+ CD64+ Ly6Clow Mϕs early in injury and that it is involved in the restoration of the epithelial barrier. We found that a lack of IL-10, particularly its secretion by Mϕs, compromised the recovery of SI epithelial barrier. IL-10 production by MHCII+ CD64+ Ly6Clow Mϕs in the SI is not regulated by the gut microbiota, hence depletion of the microbiota did not influence epithelial regeneration in the SI. Collectively, these results highlight the critical role IL-10-producing Mϕs play in recovery from intestinal epithelial injury induced by NSAID.
Intestinal fibrosis is a severe complication in patients with Crohn’s disease (CD). Unfortunately, the trigger leading to the development of intestinal fibrosis in the context of CD remains elusive. Here, we show that colonization by a CD-associated pathobiont adherent-invasive Escherichia coli (AIEC) promotes the development of intestinal fibrosis. Exogenously inoculated AIEC strain LF82 and commensal E. coli HS were gradually eradicated from the intestine in healthy mice. In Salmonella - or dextran sodium sulfate-induced colitis models, AIEC exploited inflammation and stably colonize the gut. Consequently, persistent colonization by AIEC LF82 led to substantial fibrosis. In contrast, commensal E. coli HS was unable to derive a growth advantage from inflammation, thereby failing to colonize the inflamed intestine or promote intestinal fibrosis. AIEC colonization potentiated the expression of the IL-33 receptor ST2 in the intestinal epithelium, which is crucial for the development of intestinal fibrosis. The induction of ST2 by AIEC LF82 was mediated by flagellin, as the FliC mutant failed to induce ST2. These observations provide novel insights into pathobiont-driven intestinal fibrosis and can lead to the development of novel therapeutic approaches for the treatment of intestinal fibrosis in the context of CD that target AIEC and/or its downstream IL-33-ST2 signaling.
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