Ding Yingying, Hou Yingjian, Lao Xingzhen
School of Life Science and Technology, China Pharmaceutical University, Nanjing, Jiangsu, China.
The Public Laboratory Platform of China Pharmaceutical University, Nanjing, Jiangsu, China.
Probiotics Antimicrob Proteins. 2025 Jul 9. doi: 10.1007/s12602-025-10642-y.
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.
近年来，嗜黏蛋白阿克曼氏菌（A. muciniphila）作为核心肠道共生菌的代表，因其独特的黏蛋白降解能力和宿主相互作用机制，在微生态干预领域展现出卓越的治疗潜力。A. muciniphila于2004年首次从人类粪便中分离出来。它定殖于肠道黏液层，利用杯状细胞分泌的黏蛋白作为主要碳源和氮源。2013年，研究人员发现补充A. muciniphila可改善肥胖，这证明了A. muciniphila在疾病治疗中的潜力。近期研究表明，A. muciniphila通过多种机制增强肠道屏障完整性、改善代谢性疾病并减轻炎症，这些机制包括通过Toll样受体（TLR）2刺激激活腺苷酸活化蛋白激酶（AMPK）途径以及激活含NOD样受体家族的吡咯结构域蛋白3（NLRP3）。A. muciniphila及其衍生物还具有强大的抗肿瘤作用。它们诱导肿瘤坏死因子相关凋亡诱导配体（TRAIL）上调，触发肿瘤细胞的外源性（死亡受体介导）和内源性（线粒体）凋亡途径。此外，A. muciniphila通过激活NLRP3促进M1样肿瘤相关巨噬细胞（TAM）生成，并通过与肿瘤内微生物群的代谢串扰重塑肿瘤微环境。值得注意的是，A. muciniphila与程序性死亡-1（PD-1）抗体联合使用可增强CD8 T细胞浸润，从而克服宿主对PD-1阻断的抗性。此外，A. muciniphila有助于产丁酸细菌的生长，并抑制特定细菌种群的生长，在肠道微生物群网络中发挥重要作用。本综述评估了关于A. muciniphila在维持肠道屏障完整性、改善代谢和炎症紊乱以及增强抗肿瘤免疫反应方面的多方面作用的最新发现。我们还讨论了其对肠道微生物群的生态影响，并指出了治疗局限性和前景，为促进嗜黏蛋白阿克曼氏菌在临床疾病尤其是肿瘤治疗中的发展提供理论参考。
