(P22-030-25) Impact of Akkermansia muciniphila and Its Derivatives on Tumor Progression and Immune Regulation in Mouse Models of Cancer: A Meta-Analysis of Preclinical Mouse Model Studies

Objectives: Akkermansia muciniphila (A. muciniphila) is a beneficial bacterium in the human gut known for maintaining metabolic health and immune function. Recent studies have suggested its potential as a therapeutic agent in cancer management. This meta-analysis investigates the effect of A. muciniphila and its derivatives, including Amuc protein and extracellular vesicles (EVs), on cancer outcomes in mouse models.

Methods: A total of 16 studies were included through searches on PubMed, Web of Science, Science Direct, and Embase until January 2025. Data on tumor number, volume, weight, and immune responses were extracted and analyzed. A subgroup analysis evaluated the effectiveness of live and non-live interventions, including heat-killed A. muciniphila bacteria, Amuc protein, and EVs.

Results: A. muciniphila and its derivatives significantly reduced tumor count, volume, and weight across a range of cancer types, including intestinal tumors, colorectal tumorigenesis, prostate cancer, lung cancer, gastric cancer, hepatocellular carcinoma, and ovarian cancer. Additionally, treatment groups exhibited significant increases in CD8+ T cells and interferon-gamma (IFN-γ) levels. Subgroup analysis revealed that both live A. muciniphila and non-live interventions, including heat-killed A. muciniphila, Amuc protein, and EVs, significantly reduced tumor numbers. However, only non-live interventions were significantly effective in reducing tumor weight and volume and enhancing immune responses.

Conclusions: A. muciniphila and its derivatives exhibit significant potential as therapeutic agents in cancer management. Their effects are mediated through the modulation of inflammatory pathways, apoptotic processes, microbiota composition, and immune regulation. These findings suggest that A. muciniphila could be a promising next-generation probiotic for cancer therapy, particularly in its non-live forms. Further exploration of A. muciniphila's metabolites and outer membrane proteins could unlock new therapeutic opportunities.

Funding Sources: Florida Department of Health (24K08)