Akkermansia muciniphila and Its Bioactive Derivatives: Emerging Regulators of Healthy Aging

Vollständiger Abstract

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ABSTRACT The global aging trend underscores the urgent need for innovative interventions against aging‐related decline. Accumulating evidence identifies Akkermansia muciniphila ( A. muciniphila ) as a key gut microbiota regulator of aging, with its depletion associated with age‐related diseases (ARDs), whereas its abundance is enriched in healthy centenarians. This review summarized current evidence linking A. muciniphila to aging, examining their causal relationship, the roles of its bioactive derivatives, underlying mechanisms in aging and ARDs, findings from human clinical trials, and challenges in therapeutic translation. Clinically, A. muciniphila depletion correlated with aging and various ARDs, while its supplementation effectively ameliorated neurodegenerative disorders, metabolic dysfunction, musculoskeletal decline, intestinal barrier dysfunction, and atherosclerosis. Mechanistically, A. muciniphila and its derivatives (Amuc_1100, Amuc_1409, extracellular vesicles, and metabolites such as SCFAs) exerted anti‐aging effects by enhancing intestinal barrier function, maintaining metabolic homeostasis, suppressing chronic inflammation, and modulating immune function, ultimately improving glucolipid metabolism, insulin sensitivity, cognitive function, musculoskeletal health, and vascular health. Emerging clinical trials further demonstrated its translational potential in ameliorating age‐related sarcopenia, metabolic dysfunction, and respiratory symptoms. Despite promising preclinical and clinical results, translational applications reserve challenges related to strain heterogeneity, antimicrobial resistance gene transfer risk, biosafety, production stability, and limited clinical validation in elderly populations. Future research should prioritize large‐scale clinical trials to establish optimal dosage, safety, and long‐term efficacy, while exploring combined microbiota‐targeted therapies. Harnessing the diverse benefits of A. muciniphila may enable novel strategies for promoting healthy aging.