Abstract
Akkermansia muciniphila (A. muciniphila), a health-promoting bacterium in the human gut, is recognized for its role in improving immune function and metabolic health. Recent studies have uncovered its potential use as a therapeutic intervention for cancer treatment. This meta-analysis examines the impact of A. muciniphila, its extracellular vesicles (EVs), and Amuc protein on cancer outcomes in preclinical cancer models. Sixteen studies were included in the analysis through searches of relevant databases as of July 2025. Data on tumor number, volume, weight, and immune responses were extracted and analyzed. A. muciniphila and its derivatives significantly reduced tumor metrics across various cancers, including intestinal, colorectal, prostate, lung, gastric, hepatocellular, and ovarian. The intervention elevated interferon-gamma (IFNγ), CD8⁺ T cells, TNFα, and reduced IL-10 in the tumor microenvironment. Reduced spleen weight and systemic IL-6 levels indicated both local and systemic modulation of inflammation. Dose-specific effects included more substantial reductions in tumor number, size, and spleen weight at low doses (≤ 10⁸ CFU), as well as decreased tumor cell proliferation at high doses (≥ 10⁹ CFU). A. muciniphila and its derivatives exhibit significant potential in reducing cancer metrics. Their effects are mediated by regulating tumor growth, modulating both tumor microenvironment and systemic inflammatory pathways, enhancing immune regulation, and affecting gut microbiota composition. These results suggest that A. muciniphila may be a promising next-generation adjunct therapy for cancer, particularly in its non-live forms. Further exploration of the role of A. muciniphila's outer membrane proteins and metabolites through comprehensive clinical studies could unlock new therapeutic opportunities.