Akkermansia muciniphila WW001 protects against DSS-induced colitis by restoring intestinal barrier integrity and modulating inflammatory responses.

Inflammatory bowel disease (IBD) is a chronic, relapsing disorder intimately linked to impaired intestinal barrier function. Akkermansia muciniphila, a beneficial gut bacterium, has been shown to enhance intestinal barrier function. This study aimed to characterize a newly identified strain, A. muciniphila WW001, and evaluate its protective effects on intestinal barrier integrity in IBD models. Lipopolysaccharide (LPS)-induced Caco-2/HT29-MTX cell model and dextran sulfate sodium (DSS)-induced mouse model were employed to assess its protective effects on intestinal barrier function. Whole-genome sequencing, comparative genomic analysis, and molecular docking were performed to explore the unique genetic characteristics of WW001. In line with these genomic features, WW001 significantly strengthened intestinal barrier function and displayed distinct functional characteristics compared with A. muciniphila ATCC 835, as evidenced by elevated transepithelial electrical resistance (TEER), reduced paracellular permeability, upregulation of tight junction proteins, suppression of pro-inflammatory cytokines, and elevation of anti-inflammatory cytokine levels. Furthermore, WW001 alleviated colitis symptoms and promoted goblet cell proliferation, which were associated with its distinct genomic features and increased short-chain fatty acid (SCFA) concentrations. The enriched glycoside hydrolase repertoire may indicate an enhanced capacity for mucin-derived glycan utilization; however, the causal relationships among these genomic features, mucin utilization, SCFA changes, and barrier protection remain to be established. These findings demonstrate that A. muciniphila WW001 enhances intestinal barrier function and exerts anti-inflammatory effects, while the associated metabolic changes may contribute to its beneficial effects, supporting its potential application as a probiotic candidate for IBD intervention.