Journal Article

5-aminosalicylic acid alleviates colitis and protects intestinal barrier function by modulating gut microbiota in mice

Wan, Leilei, Wang, Xiaoxin, Jiang, Mingjie, Wang, Jingjing, Dai, Juanjuan, Lang, Tao

2025

Overview

5-aminosalicylic acid (5-ASA) is widely used in the treatment of ulcerative colitis (UC), but its anti-inflammatory mechanism is complex and has not been fully understood. DSS model was used to test the effect of 5-ASA. Tight junction and Ki-67 were detected by western blot, immunofluorescence, and immunohistochemistry or qPCR. 16S rRNA gene sequencing of gut microbiota and subsequent bioinformatics and statistical analysis were performed to identify the specific bacteria which were associated with the treatment effect of 5-ASA. GC-MS was performed to test short-chain fatty acids (SCFAs). Antibiotic-treated mice were used to demonstrate the key role of endogenous gut microbiota. Here, we found that 5-ASA alleviated dextran sulfate sodium (DSS)-induced colitis in mice. Moreover, 5-ASA significantly repaired the intestinal barrier. At the molecular level, 5-ASA markedly raised the expression of tight junction proteins including JAM-A and occludin and cell proliferation marker Ki-67 in mice. In addition, bacterial 16S rRNA gene sequencing and bioinformatics analysis showed that 5-ASA significantly modulated the DSS-induced gut bacterial dysbiosis. In detail, it stimulated the growth of protective bacteria belonging to Faecalibaculum and Dubosiella , which were negatively correlated with colitis parameters, and blocked the expansion of pro-inflammatory bacteria such as Escherichia-Shigella and Oscillibacter , which were positively correlated with colitis in mice. Meanwhile, 5-ASA increased the cecal acetate level. Most notably, 5-ASA was no longer able to treat colitis and reverse gut barrier dysfunction in antibiotic-treated mice that lacked endogenous gut microbiota. Our data suggested that the anti-inflammatory activity of 5-ASA required the inherent intestinal flora, and the gut microbiota was a potential and effective target for the treatment of ulcerative colitis.

• Publisher: Springer Berlin Heidelberg,Springer Nature B.V
• Subject: Acetic acid / Animals / Anti-inflammatory agents / Anti-Inflammatory Agents, Non-Steroidal - pharmacology / Anti-Inflammatory Agents, Non-Steroidal - therapeutic use / Antibiotics / Bacteria / Bioinformatics / Biomedical and Life Sciences / Biomedicine / Cecum / Cell proliferation / Colitis - chemically induced / Colitis - drug therapy / Colitis - metabolism / Colitis - microbiology / Colitis, Ulcerative - drug therapy / Colon - drug effects / Colon - metabolism / Colon - microbiology / Colon - pathology / Dextran / Dextran Sulfate / Digestive system / Disease Models, Animal / DNA sequencing / Dysbacteriosis / Dysbiosis - drug therapy / Gastrointestinal Microbiome - drug effects / Gastrointestinal tract / Gut microbiota / Immunofluorescence / Immunohistochemistry / Inflammatory bowel disease / Inflammatory bowel diseases / Intestinal Barrier Function / Intestinal microflora / Intestinal Mucosa - drug effects / Intestinal Mucosa - metabolism / Intestinal Mucosa - microbiology / Male / Mesalamine - pharmacology / Mesalamine - therapeutic use / Mice / Mice, Inbred C57BL / Microbiota / Neurosciences / Pharmacology/Toxicology / RNA, Ribosomal, 16S - genetics / rRNA 16S / Statistical analysis / Tight Junction Proteins - metabolism / Tight Junctions - drug effects / Tight Junctions - metabolism / Ulcerative colitis