The Role of Akkermansia muciniphila in Disease Regulation

In recent years, Akkermansia muciniphila (A. muciniphila), as a representative of the core gut commensal bacteria, has shown outstanding therapeutic potential in the field of microecological interventions due to its unique mucin degrading ability and host-interaction mechanism. A. muciniphila is first isolated from human feces in 2004. It colonizes the intestinal mucus layer, utilizing mucin secreted by goblet cells as its primary carbon and nitrogen source. In 2013, researchers found that supplementation with A. muciniphila could improve obesity, demonstrating the potential of A. muciniphila in the treatment of disease. Recent studies show that A. muciniphila strengthens intestinal barrier integrity, improves metabolic diseases, and mitigates inflammation through multiple mechanisms, including adenosine monophosphate-activated protein kinase (AMPK) pathway activation via Toll-like receptor (TLR) 2 stimulation and NOD-like receptor family, pyrin domain containing 3 (NLRP3) activation. A. muciniphila and its derivatives also exhibit potent anti-tumor effects. They induce tumor-necrosis-factor-related apoptosis-inducing ligand (TRAIL) upregulation, triggering extrinsic (death receptor-mediated) and intrinsic (mitochondrial) apoptosis pathways in tumor cells. Additionally, A. muciniphila promotes M1-like tumor-associated macrophages (TAMs) through NLRP3 activation and remodels the tumor microenvironment via metabolic crosstalk with intratumoral microbiota. Notably, A. muciniphila combined with programmed death-1 (PD-1) antibody boost CD8⁺ T cell infiltration, thereby overcoming host resistance to PD-1 blockade. Moreover, A. muciniphila contributes to the growth of butyric acid-producing bacteria and suppresses the growth of specific bacterial populations, playing an important role in the gut microbiome network. This review evaluates recent discoveries regarding A. muciniphila's multifaceted roles in maintaining intestinal barrier integrity, ameliorating metabolic and inflammatory disorders, and enhancing anti-tumor immune responses. We also discuss its ecological effect on the gut microbiota flora and point out the therapeutic limitations and prospect which provides theoretical references to promote the development of Akkermansia muciniphila in clinical diseases, especially in tumor therapy.