Fecal microbiota transplantation improves intestinal inflammation in mice with ulcerative colitis by modulating intestinal flora composition and down-regulating NF-kB signaling pathway.

Ulcerative colitis (UC) is a chronic inflammatory disease of the intestine. It is characterized with recurrent. The pathogenesis is mainly associated with environmental factors, genetic susceptibility, dysbiosis of the intestinal flora and autoimmunity. The role of intestinal flora disorders in the pathogenesis and progression of UC is becoming increasingly prominent. More and more studies have confirmed that fecal microbiota transplantation (FMT) could reshape the composition of UC intestinal flora and it is expected to be a new strategy for UC treatment. In this study, we used 2% Dextran sulfate sodium (DSS) for 7 days to induce acute colitis model in mice, and interfere with FMT and Enterotoxigenic Escherichia coli (ETEC). ELISA and immunohistochemistry were applied to detect the concentration and expression of NF-κB p65, STAT3 and IL-6. 16SrRNA high-throughput sequencing was performed to explore the composition of intestinal flora. The aim was to study the treatment effect of FMT on UC mice and explore its potential mechanism by observing the changes of intestinal flora composition and diversity, and its relationship with NF-κB p65, STAT3 and IL-6 expression. We conclude that FMT could improve intestinal flora disorder in mice with ulcerative colitis, regulate NF-κB signaling pathway, and significantly reduce intestinal inflammation in UC mice.

Integrative analysis revealed the role of glucagon-like peptide-2 in improving experimental colitis in mice by inhibiting inflammatory pathways, regulating glucose metabolism, and modulating gut microbiota.

Introduction: Ulcerative colitis (UC) is an inflammatory bowel disease characterized by recurrent and remitting inflammation of the mucosa of the colon and rectum, the incidence of which is on the rise. Glucagon-like peptide-2 (GLP-2) is a newly discovered neurotrophic factor, but its efficacy and mechanism of action in UC remain unclear. In this study, we investigated the protective effects and potential targets of GLP-2 on dextran sodium sulfate (DSS)-induced UC in mice through integrative analysis. Methods: The effects of GLP-2 on UC were assessed by calculating the disease activity index, colonic mucosal damage index, and pathological histological scores. Enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry were used to detect the expression of GLP-2, nuclear factor kappa-B (NF-κB), interleukin-6 (IL-6), and signal transducer and activator of transcription-3 (STAT3). The 16SrRNA gene was used to detect changes in gut microbiota in mouse colonic tissues, and oral glucose tolerance test (OGTT) blood glucose levels were used to analyze the differences in flora. Results: The results showed that GLP-2 could reduce the inflammation of UC mice, which may be achieved by inhibiting the potential targets of NF-κB, and Janus kinase (JAK)/STAT3 inflammatory pathways, regulating sugar metabolism, increasing dominant species, and improving microbial diversity. Discussion: This study provides new insight into the potential of GLP-2 for achieving more ideal UC treatment goals in future.