Mucosa-associated bacteria and metabolites in inflammatory bowel disease: from inside to insight

Inflammatory bowel disease (IBD) involves chronic gastrointestinal inflammation with complex etiologies, where gut microbiota and metabolites have emerged as key pathogenic factors. While earlier studies predominantly focused on fecal bacteria, recent research has shifted to mucosa-associated bacteria, which reside in the intestinal mucus layer and directly interact with the epithelium-critical for IBD pathogenesis. This review synthesizes evidence showing that IBD patients exhibit mucosa-associated bacteria dysbiosis, characterized by increased facultative anaerobes and reduced beneficial taxa, alongside altered mucosal metabolites such as short-chain fatty acids (SCFAs) and trimethylamine-N-oxide (TMAO). Notably, mucosa-associated bacteria-driven metabolic changes show promise as early diagnostic markers for IBD. Mechanistically, mucosa-associated bacteria directly modulate intestinal barrier integrity and immune responses via pathways like TLR4-mediated inflammation and mucin degradation, distinct from luminal microbiota studied in fecal samples. This review highlights novel therapeutic strategies targeting mucosa-associated bacteria and mucosal metabolites, including probiotics, phage therapy against AIEC, and nanoparticle-based drug delivery systems for localized anti-inflammatory action. Understanding the mucosa-specific microbiota-metabolite-host interactions is pivotal for advancing precision medicine in IBD, bridging gaps in prior fecal-focused research.