Bacteroides uniformis-induced perturbations in colonic microbiota and bile acid levels inhibit TH17 differentiation and ameliorate colitis developments

Abstract

Inflammatory bowel disease (IBD) is associated with gut dysbiosis and can lead to colitis-associated malignancies. Bacteroides uniformis (Bu) regulates animal intestinal homeostasis; however, the mechanism by which it alleviates colitis in mice remains unknown. We investigated the effects of B. uniformis JCM5828 and its metabolites on female C57BL/6J mice with dextran sulfate sodium salt (DSS) induced colitis. Treatment with Bu considerably alleviated colitis progression and restored the mechanical and immune barrier protein expression. Additionally, Bu increased the abundance of the symbiotic bacteria Bifidobacterium and Lactobacillus vaginalis while decreasing that of pathogenic Escherichia-Shigella, and modulated intestinal bile acid metabolism. Bu largely regulated the expression of key regulatory proteins of the NF-κB and mitogen-activated protein kinase (MAPK) signaling pathways in colonic tissues and the differentiation of TH17 cells. However, Bu could not directly inhibit TH17 cell differentiation in vitro; it modulated the process in the lamina propria by participating in bile acid metabolism and regulating key metabolites (alpha-muricholic, hyodeoxycholic, and isolithocholic acid), thereby modulating the intestinal immune response. Our findings suggest that Bu or bile acid supplements are potential therapies for colitis and other diseases associated with intestinal barrier dysfunction.

Mechanistic insights into the role of probiotics in modulating immune cells in ulcerative colitis

“…Instead, it seemed to influence this process inside the lamina propria, indicating a multifaceted mechanism. 75 The results suggest that Bu or bile acid supplements may have promise as therapeutic interventions for colitis and other conditions characterized by impaired intestinal barrier function. The potential therapeutic efficacy of Bu is attributed to its impact on bile acid metabolism, gut microbiota, and immunological modulation.…”

“…137 This investigation's findings demonstrated that Bu's administration effectively mitigated the advancement of colitis, indicating its potential protective efficacy in the DSS-mouse model. 75 Additionally, the Bu therapy has shown the ability to reinstate the production of mechanical and immunological barrier proteins, which are often disrupted in cases of colitis. 75 This suggests that Bu might help preserve the intestinal barrier's integrity.…”

“…75 Additionally, the Bu therapy has shown the ability to reinstate the production of mechanical and immunological barrier proteins, which are often disrupted in cases of colitis. 75 This suggests that Bu might help preserve the intestinal barrier's integrity. Furthermore, Bu therapy was linked to a rise in the number of good bacteria such as Bifidobacterium and Lactobacillus vaginalis while decreasing the prevalence of pathogenic microbes and reducing the abundance of pathogenic Escherichia-Shigella.…”

“…It controlled important metabolites such as hyodeoxycholic, isolithocholic acid, and alpha-muricholic. 75 Bile acids are involved in many physiological activities, including immunological control. Furthermore, the findings of this research indicate that Bu exerted a notable influence on the modulation of essential regulatory proteins involved in the NF-κB and mitogenactivated protein kinase signaling pathways in colonic tissues.…”

“…Furthermore, the findings of this research indicate that Bu exerted a notable influence on the modulation of essential regulatory proteins involved in the NF-κB and mitogenactivated protein kinase signaling pathways in colonic tissues. 75 Furthermore, it impacted the differentiation process of TH17 cells, which have been linked to inflammatory responses. Nevertheless, Bu did not directly impede the development of TH17 cells in a laboratory setting.…”