Integrated gene-catalog and genome-resolved metagenomics reveal taxonomic and metabolic differences in the gut microbiome in irritable bowel syndrome

Background: Irritable bowel syndrome is a common gastrointestinal disorder with heterogeneous symptoms and incompletely understood pathophysiology. Gut microbiome dysbiosis has been repeatedly associated with IBS, but the extent to which taxonomic changes are accompanied by gene-level and genome-resolved differences in microbial functional potential and inferred microbial community structure remains unclear. Results: We conducted a case-control shotgun metagenomic study of stool samples from patients with IBS and healthy controls. Taxonomic profiling identified distinct IBS associated compositional patterns, including enrichment of Klebsiella pneumoniae and Streptococcus parasanguinis and depletion of SCFA-associated taxa such as Phascolarctobacterium and Faecalibacterium prausnitzii. Overall microbial community composition differed between IBS and healthy controls. Assembly-based analysis generated a cohort-specific catalog of 934,495 nonredundant microbial genes. Functional profiling identified differences in carbohydrate-active enzyme families involved in dietary and host-derived glycan metabolism. Genome-resolved analysis recovered 154 nonredundant high-quality metagenome-assembled genomes and identified distinct taxonomic patterns, including HC associated Bifidobacterium longum and IBS associated Dialister invisus, CAG-177 sp003538135, and CAG-568 sp000434395. Metabolic analysis of the recovered genomes further revealed IBS associated enrichment of pathways related to fatty acid biosynthesis and elongation, de novo purine biosynthesis, and histidine degradation. Together, these findings demonstrate that IBS-associated microbiome differences extend beyond community composition to gene-level and genome-resolved functional potential. Conclusions: This study provides a multilayered view of the IBS gut microbiome by integrating read-based taxonomic profiling, a cohort-specific microbial gene catalog, functional annotation, genome-resolved reconstruction, and metabolic-module analysis. IBS was characterized by depletion of SCFA-associated taxa, enrichment of facultative anaerobic and opportunistic taxa, altered representation of carbohydrate-active enzyme families, and distinct genome-resolved metabolic patterns. The convergence of taxonomic, gene-catalog, and MAG-level findings highlights coordinated differences in microbial composition and encoded metabolic potential in IBS and identifies candidate microbial populations and functions for validation in larger cohorts and targeted mechanistic studies.