Indole-3-acetic acid alleviates DSS-induced colitis by promoting the production of R-equol from Bifidobacterium pseudolongum

• Published in: Gut microbes Vol. 16; no. 1; p. 2329147
• Main Authors: Li, Miaomiao, Han, Xue, Sun, Lijun, Liu, Xinjuan, Zhang, Weizhen, Hao, Jianyu
• Format: Journal Article
• Language: English
• Published: United States Taylor & Francis 2024; Taylor & Francis Group
• Subjects: Animals; Bifidobacterium; bifidobacterium pseudolongum; colitis; Colitis - chemically induced; Colitis - drug therapy; Colitis - metabolism; Colon - metabolism; Dextran Sulfate - toxicity; Disease Models, Animal; Equol - metabolism; Equol - pharmacology; Equol - therapeutic use; Forkhead Transcription Factors - genetics; Forkhead Transcription Factors - metabolism; Forkhead Transcription Factors - pharmacology; Gastrointestinal Microbiome; gut microbiome; IAA; Indoleacetic Acids - metabolism; Inflammation - pathology; Inflammatory Bowel Diseases - pathology; Mice; Mice, Inbred C57BL; regulatory T cells; Research Paper; RNA, Ribosomal, 16S - genetics; regulatory T cells; IAA; bifidobacterium pseudolongum; colitis; gut microbiome
• ISSN: 1949-0976; 1949-0984; 1949-0984
• DOI: 10.1080/19490976.2024.2329147

Inflammatory bowel disease (IBD) is characterized by immune-mediated, chronic inflammation of the intestinal tract. The occurrence of IBD is driven by the complex interactions of multiple factors. The objective of this study was to evaluate the therapeutic effects of IAA in colitis. C57/BL6 mice were administered 2.5% DSS in drinking water to induce colitis. IAA, and R-equol were administered by oral gavage and fed a regular diet. The Disease Activity Index was used to evaluate disease activity. The degree of colitis was evaluated using histological morphology, RNA, and inflammation marker proteins. CD45+ CD4+ FOXP3+ Treg and CD45+ CD4+ IL17A+ Th17 cells were detected by flow cytometry. Analysis of the gut microbiome in fecal content was performed using 16S rRNA gene sequencing. Gut microbiome metabolites were analyzed using Untargeted Metabolomics. In our study, we found IAA alleviates DSS-induced colitis in mice by altering the gut microbiome. The abundance of significantly increased in the IAA treatment group. ATCC25526 alleviates DSS-induced colitis by increasing the ratio of Foxp3+T cells in colon tissue. R-equol alleviates DSS-induced colitis by increasing Foxp3+T cells, which may be the mechanism by which ATCC25526 alleviates DSS-induced colitis in mice. Our study demonstrates that IAA, an indole derivative, alleviates DSS-induced colitis by promoting the production of Equol from which provides new insights into gut homeostasis regulated by indole metabolites other than the classic AHR pathway.