Multi-matrix metabolome and microbiome profiling in diarrhea-predominant irritable bowel syndrome and ulcerative colitis in remission with IBS-like symptoms

Background

Irritable bowel syndrome (IBS)-like symptoms frequently persist in patients with ulcerative colitis (UC) in remission. Whether UC in remission with IBS-like symptoms (UCR-IBS) represents functional overlap with diarrhea-predominant IBS (IBS-D) or a distinct metabolic phenotype remains unclear.

Methods

In this exploratory cross-sectional study, 39 patients with IBS-D, 21 with UCR-IBS, and 35 healthy controls were enrolled. Serum, urine, fecal, and colonic mucosal samples were collected. Untargeted metabolomics, targeted tryptophan profiling, fecal 16S ribosomal RNA gene sequencing, predicted microbial functional profiling, and microbe-metabolite association analyses were performed.

Results

Tryptophan-related metabolism was altered in both patient groups, but the patterns differed across biological matrices. Compared with IBS-D, UCR-IBS showed higher serum N-formylkynurenine (NFK) concentrations, and fecal findings suggested reduced concentrations of microbiota-associated indole metabolites. Microbiome differences were modest, but predicted nicotinate/nicotinamide metabolism was enriched in UCR-IBS. Exploratory network analysis identified associations between tryptophan-related metabolites and selected bacterial genera in each group.

Conclusions

Multi-matrix profiling shows tryptophan-related metabolic differences between mesalazine-treated UCR-IBS and IBS-D, highlighting higher serum NFK concentrations in UCR-IBS. These findings provide a basis for investigating host-microbiota metabolic relationships across systemic and intestinal compartments during UC remission.

This trial was registered in the Chinese Clinical Trial Registry (ChiCTR; https://www.chictr.org.cn/) under registration number ChiCTR2200060224.