Zhang Yifei, Liu Ruixin, Chen Yufei, Cao Zhiwen, Liu Cong, Bao Riqiang, Wang Yufan, Huang Shan, Pan Shijia, Qin Li, Wang Jiqiu, Ning Guang, Wang Weiqing
Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, National Clinical Research Center for Metabolic Diseases (Shanghai), Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission, Shanghai Key Laboratory for Endocrine Tumor, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
Department of Endocrinology and Metabolism, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China.
Cell Metab. 2025 Mar 4;37(3):592-605.e6. doi: 10.1016/j.cmet.2024.12.010. Epub 2025 Jan 28.
Akkermansia muciniphila is a promising target for managing obesity and type 2 diabetes (T2D), but human studies are limited. We conducted a 12-week randomized, double-blind, placebo-controlled trial involving 58 participants with overweight or obese T2D, who received A. muciniphila (AKK-WST01) or placebo, along with routine lifestyle guidance. Both groups showed decreases in body weight and glycated hemoglobin (HbA1c), without significant between-group differences. In participants with low baseline A. muciniphila, AKK-WST01 supplementation showed high colonization efficiency and significant reductions in body weight, fat mass, and HbA1c, which were not found in the placebo group. However, AKK-WST01 supplementation showed poor colonization and no significant clinical improvements in participants with high baseline A. muciniphila. These findings were verified in germ-free mice receiving feces with low or high A. muciniphila. Our study indicates that metabolic benefits of A. muciniphila supplementation could depend on its baseline intestinal levels, supporting the potential for gut microbiota-guided probiotic supplementation. (ClinicalTrials.gov number, NCT04797442).
嗜黏蛋白阿克曼氏菌是治疗肥胖症和2型糖尿病（T2D）的一个有前景的靶点，但人体研究有限。我们进行了一项为期12周的随机、双盲、安慰剂对照试验，纳入了58名超重或肥胖的T2D参与者，他们接受了嗜黏蛋白阿克曼氏菌（AKK-WST01）或安慰剂，并接受常规生活方式指导。两组的体重和糖化血红蛋白（HbA1c）均有所下降，组间差异不显著。在基线嗜黏蛋白阿克曼氏菌水平较低的参与者中，补充AKK-WST01显示出高定殖效率，体重、脂肪量和HbA1c显著降低，而安慰剂组未发现这些情况。然而，在基线嗜黏蛋白阿克曼氏菌水平较高的参与者中，补充AKK-WST01显示出定殖不佳，且无显著的临床改善。这些发现在用低或高嗜黏蛋白阿克曼氏菌粪便接种的无菌小鼠中得到了验证。我们的研究表明，补充嗜黏蛋白阿克曼氏菌的代谢益处可能取决于其肠道基线水平，这支持了肠道微生物群指导的益生菌补充的潜力。（ClinicalTrials.gov编号，NCT04797442）
