Dietary Nondigestible Polysaccharides Ameliorate Colitis by Improving Gut Microbiota and CD4⁺ Differentiation, as Well as Facilitating M2 Macrophage Polarization

Abstract

Background The aim of this study was to investigate the therapeutic mechanism of a specific multifiber mix diet (MF) designed to match the fiber content of a healthy diet in interleukin‐10 knockout (IL‐10−/−) mice with spontaneous chronic colitis displaying similar characteristics to those of human Crohn's disease (CD). Methods Sixteen‐week‐old IL‐10−/− mice were used for the experiments with MF diet for 4 weeks. Severity of colitis, the composition of the fecal microbiota, expression of Th1/Th17 cells, myeloperoxidase (MPO) concentrations, and inflammatory cytokines and chemokines (tumor necrosis factor‐α [TNF‐α], IL‐6, macrophage inflammatory protein [MIP]‐2, monocyte chemoattractant protein‐1 [MCP‐1], and MIP‐1α), as well as arginase 1 (Arg1) and signal transducers and activators of transcription 6 (STAT6) proteins, were measured at the end of the experiment. In addition, the corresponding metabolites (short‐chain fatty acids) of MF on CD4+CD25+Foxp3+ regulatory T cells (Tregs) were also detected in vivo and in vitro. Results MF treatment significantly ameliorated colitis associated with decreased lamina propria frequency of Th1/Th17 cells, MPO concentrations, and inflammatory cytokines and chemokines (TNF‐α, IL‐6, MIP‐2, MCP‐1, and MIP‐1α). An increase in gut microbial diversity was observed after MF treatment compared with IL‐10−/− mice, including a significant increase in bacteria belonging to the Firmicutes phylum and a significant decrease in bacteria belonging to the Proteobacteria phylum. Moreover, MF treatment increased the differentiation of CD4+CD25+Foxp3+ Tregs mainly by microbial metabolites butyrate. In addition, Arg1 and STAT6 proteins were also significantly increased after MF treatment. Conclusions These results shed light on the contribution of MF treatment to the CD mouse model and suggest that MF has potential as a therapeutic strategy for enhancing efficacy in inducing remission in patients with active CD.

Probiotic Bacillus cereus Alleviates Dextran Sulfate Sodium-Induced Colitis in Mice through Improvement of the Intestinal Barrier Function, Anti-Inflammation, and Gut Microbiota Modulation

“…Several studies have demonstrated that dysregulated intestinal immune response and mucosal inflammation induced by dysbiosis also contribute to mucosal epithelial barrier dysfunction and progression of IBD. , In particular, the regulation of macrophage polarization through the transplantation of gut microbiota is a promising effective target for colitis. , In addition, intestinal inflammation during the development of colitis is characterized by enhanced pro-inflammatory cytokines levels . Furthermore, the toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-κB) and NOD-like receptor pyrin domain-containing protein 3 (NLRP3) inflammasome signaling pathways mediate the pathogenesis of intestinal inflammation. , Thus, the macrophage polarization modulation and inflammatory cytokine production by modulating various inflammatory signaling pathways can be a potential therapeutic approach for colitis.…”

“…7,8 In particular, the regulation of macrophage polarization through the transplantation of gut microbiota is a promising effective target for colitis. 9,10 In addition, intestinal inflammation during the development of colitis is characterized by enhanced pro-inflammatory cytokines levels. 11 Furthermore, the toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-κB) and NOD-like receptor pyrin domain-containing protein 3 (NLRP3) inflammasome signaling pathways mediate the pathogenesis of intestinal inflammation.…”

Review article: The complex interplay between diet and Escherichia coli in inflammatory bowel disease

“…Together these observations suggest that background diet composition can abrogate the protective properties of FOS. Wang et al 51 investigated the effectiveness of a 4‐week multifibre mix diet, including 49% FOS, in IL‐10−/− mice with spontaneous colitis. A significant decrease in colitis was observed which was associated with reduction of Th1/Th17 cells in lamina propria, reduced inflammatory cytokines and chemokines, and a decrease in members of Proteobacteria in faecal samples.…”