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Ring1a protects against colitis through regulating mucosal immune system and colonic microbial ecology.

ABSTRACT: Inflammatory bowel disease (IBD) represents a prominent chronic immune-mediated inflammatory disorder, yet its etiology remains poorly comprehended, encompassing intricate interactions between genetics, immunity, and the gut microbiome. This study uncovers a novel colitis-associated risk gene, namely Ring1a, which regulates the mucosal immune response and intestinal microbiota. Ring1a deficiency exacerbates colitis by impairing the immune system. Concomitantly, Ring1a deficiency led to a Prevotella genus-dominated pathogenic microenvironment, which can be horizontally transmitted to co-housed wild type (WT) mice, consequently intensifying dextran sodium sulfate (DSS)-induced colitis. Furthermore, we identified a potential mechanism linking the altered microbiota in Ring1aKO mice to decreased levels of IgA, and we demonstrated that metronidazole administration could ameliorate colitis progression in Ring1aKO mice, likely by reducing the abundance of the Prevotella genus. We also elucidated the immune landscape of DSS colitis and revealed the disruption of intestinal immune homeostasis associated with Ring1a deficiency. Collectively, these findings highlight Ring1a as a prospective candidate risk gene for colitis and suggest metronidazole as a potential therapeutic option for clinically managing Prevotella genus-dominated colitis.

SUBMITTER: Wang Y

PROVIDER: S-EPMC10478745 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature

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Ring1a protects against colitis through regulating mucosal immune system and colonic microbial ecology.

Wang Yashu Y Li Qianru Q Zhang Jiayu J Liu Pingping P Zheng Huaixin H Chen Lijuan L Wang Zhen Z Tan Chen C Zhang Min M Zhang Hongxia H Miao Wenqing W Wang Yuke Y Xuan Xiaoyan X Yi Guoqiang G Wang Peng P

Gut microbes 20231201 2

Inflammatory bowel disease (IBD) represents a prominent chronic immune-mediated inflammatory disorder, yet its etiology remains poorly comprehended, encompassing intricate interactions between genetics, immunity, and the gut microbiome. This study uncovers a novel colitis-associated risk gene, namely Ring1a, which regulates the mucosal immune response and intestinal microbiota. Ring1a deficiency exacerbates colitis by impairing the immune system. Concomitantly, Ring1a deficiency led to a <i>Prev ...[more]

PMID: 37655448

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Project description:Background: Ulcerative colitis is characterized by relapsing and remitting mucosal inflammation. Bovine lactoferrin (BL) is a multifunctional protein that could regulate the intestinal flora and has anti-inflammatory effects. The aim of this study was to investigate the therapeutic effect of BL on colitis. Methods: Dextran sulfate sodium salt (DSS) was utilized to establish a mouse model of colitis. BL was administered to treat DSS mice. The weight, the activity, and fecal status of the mice were recorded every day. Disease activity index was calculated. After the mice were euthanized, the colon length was measured. Hematoxylin and eosin staining was used to observe the pathological changes of the colon, and histological activity index was calculated. The myeloperoxidase (MPO) activity of colon tissue was measured. Western blot and immunohistochemistry were used to detect the expressions of Claudin-1, Occludin, and ZO-1. The expressions of IL-1β, IL-6, IL-10, TNF-α, and TGF-β in colon tissue were detected by ELISA. The protein expressions of MUC2, Reg3γ, β-defensin (HBD-2), and cAMP were detected by immunofluorescence (IF). 16S rDNA sequencing determined the type and structure of intestinal flora. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) measured the metabolites of the intestinal flora. Results: Compared with the DSS group, the mice's weight in the BL group was higher and the length of the colon was longer. At the 14th day, MPO activity was higher in the BL group. The expressions of Claudin-1, Occludin, and ZO-1 in the colon were up-regulated in the BL group compared with the DSS group. The expressions of IL-1β, IL-6, and TNF-α were lower. The expressions of IL-10 and TGF-β were higher. IF showed that the expressions of MUC2 and β-defensin (HBD-2) were down-regulated, and the expressions of Reg3γ and cAMP were up-regulated. The 16S rDNA sequencing results showed that the alpha diversity and beta diversity were notably changed in the DSS mice treated with BL. Metabolomics results showed that BL changed purine metabolism in the DSS mice. Conclusion: BL alleviated colitis in mice by improving the inflammatory response and the structure of the colon barrier in the colon. BL changed the composition and metabolites of the intestinal flora. Thus, BL might be an effective nutritional supplement for colitis treatment.

Dataset Information

Ring1a protects against colitis through regulating mucosal immune system and colonic microbial ecology.

Publications

Ring1a protects against colitis through regulating mucosal immune system and colonic microbial ecology.

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