Gut microbiota, microbial metabolites, and mucosal barrier dysfunction in benign anorectal disorders and ulcerative...

Benign anorectal disorders and ulcerative colitis (UC) are typically managed as separate clinical conditions, despite growing recognition of overlapping pathophysiological features. Constipation, hemorrhoidal disease, anal fistula and colonic mucosal inflammation may converge on partially shared molecular pathways involving microbial dysbiosis, altered microbial metabolite generation, epithelial barrier impairment, immune activation, stromal remodeling and dysregulated tissue repair, although the strength of mechanistic evidence varies substantially among these conditions. This review synthesizes advances from the past decade to propose a translational molecular medicine framework for investigating potential molecular connections among anatomically distinct anorectal and colonic disorders, without assuming shared causal origins. Clinical and pathological associations between disordered defecation, hemorrhoidal vascular remodeling, fistula persistence and UC are contextualized alongside current insights into gut and anorectal microbiota dysbiosis, short-chain fatty acid signaling, bile acid metabolism, tryptophan metabolite activity, gas-producing microbial communities, mucus biology, tight junction function, innate and adaptive immune responses, and fibro-inflammatory repair processes. Integrating microbiome profiling, metabolomics, transcriptomics, single-cell and spatial analyses with causal inference provides a cross-disease framework for resolving convergent molecular states associated with recurrence, healing and therapeutic response. By moving beyond disease-by-disease description, this strategy may uncover biomarkers and actionable pathways otherwise overlooked, supporting mechanism-informed prevention, perioperative optimization and individualized intervention across anorectal disorders and inflammatory bowel disease (IBD).