The pathobiont role of Akkermansia muciniphila in colorectal cancer: a systematic review

Abstract

BackgroundColorectal cancer (CRC) is the second leading cause of cancer-related mortality worldwide. Emerging evidence highlights the gut microbiota, particularly Akkermansia muciniphila, as a key modulator in CRC pathogenesis. While often regarded as a beneficial commensal, its role in CRC appears complex and potentially dualistic.ObjectiveThis systematic review aims to comprehensively analyze the context-dependent role of A. muciniphila in CRC, evaluating its potential as a pathobiont.MethodsWe systematically reviewed human, animal, in vitro, and ex vivo studies on associations between A. muciniphila and CRC risk or outcomes. Database searches identified 34 eligible studies. Study quality was assessed using the GRADE criteria.ResultsFrom 244 initial records, 34 studies met the inclusion criteria. Findings reveal a stark dichotomy: non-viable forms of A. muciniphila-including pasteurized bacteria, outer membrane vesicles (OMVs), and purified proteins (e.g., Amuc1100, Amuc2172, Amuc1434*)-consistently demonstrate anti-tumorigenic effects. These components enhance anti-tumor immunity by activating CD8 + T cells, promoting M1-like macrophage polarization via TLR2/NLRP3 signaling, and sensitizing tumors to chemotherapy and anti-PD-1 immunotherapy. Conversely, administration of live A. muciniphila can exert pro-tumorigenic effects, particularly in inflammatory contexts (e.g., colitis-associated CRC) or post-antibiotic settings, likely due to excessive mucin degradation and gut barrier disruption. Host factors such as obesity, sex, genetics, and microbial interactions further modulate its impact.ConclusionA. muciniphila functions as a pathobiont in CRC, with its role critically dependent on its biological state and host context. Therapeutic strategies should shift from live probiotics to targeted postbiotic applications of its beneficial components to maximize efficacy and safety.