Integrative multi‐omics reveals the mechanism of ulcerative colitis treated with Ma‐Mu‐Ran antidiarrheal capsules

Rationale Ulcerative colitis (UC) is a chronic inflammatory gastrointestinal disease typically coexisting with intestinal microbiota dysbiosis, oxidative stress, and an inflammatory response. Although its underlying mechanism of action is unclear, Ma‐Mu‐Ran Antidiarrheal Capsules (MMRAC) have demonstrated significant therapeutic efficacy for UC. Methods The mechanism of action of MMRAC in the treatment of UC model was investigated by combining metabolomics, transcriptomics, and intestinal microbiota detection techniques. Results The high‐dose group of MMRAC was determined as the best therapeutic dose by pathological changes and biochemical indexes. Transcriptome analysis revealed that 360 genes were differentially altered after MMRAC treatment. Metabolomic analysis using colon tissue yielded 14 colon tissue metabolites with significant differences. Intestinal flora analysis showed that 26 major microorganisms were identified at the genus level. Conclusions Based on a thorough multi‐omics analysis of transcriptomics, metabolomics, and gut flora, it was determined that MMRAC regulated cysteine and methionine metabolism, arginine biosynthesis, and sphingolipid metabolism and their respective genes BHMT, PHGDH, iNOS, and SPHK1, which in turn served to inhibit UC‐generated inflammatory responses and oxidative stress. Additionally, MMRAC regulated the abundance of Coprococcus, Helicobacter, Sutterella, Paraprevotella, and Roseburia in the intestinal tracts of UC mice, which was regulated toward normal levels, thereby restoring normal intestinal function.