Gut Microbiota–Metabolite Signaling in Irritable Bowel Syndrome: From Mechanisms and Candidate Metabotypes to Precision Therapeutics

Irritable bowel syndrome (IBS) is a heterogeneous disorder of gut–brain interaction in which the same bowel-habit subtype can arise from different biological processes. This narrative review maps microbiota-related bile acids, short-chain fatty acids (SCFAs), tryptophan metabolites, lipopolysaccharide (LPS), neuroactive amines, and fatty acid ethanolamides to host sensors and barrier, immune, motor, and sensory outcomes. Its contribution is a pathway-specific assessment of the evidence needed for clinical use: analytical and temporal reproducibility, demonstration of the proposed mechanism in humans, and prediction of differential treatment benefit. We distinguish descriptive associations, preclinical mechanisms, human pharmacodynamic effects, and validated treatment-selection biomarkers. Bile acid dysregulation offers the most developed connection between a measurable physiological abnormality and a tractable pathway, although biomarker changes do not establish symptom benefit or validate every proposed selection threshold. Most other candidate metabotypes lack externally validated classification rules and prospective treatment-by-biomarker interaction evidence. Diet, transit, medications, sex and hormonal context, and subtype transitions can modify both microbial function and measured metabolite exposure. Accordingly, proposed metabotypes remain research constructs. We integrate microbial transformations and endocrine cross-talk with an evidence ledger that identifies the missing human and predictive links, providing a testable agenda for mechanism-based treatment rather than a clinically validated prescribing algorithm.