许多研究报告了肠道微生物群在肥胖中的关键作用。然而，导致肥胖的具体微生物及其潜在机制仍未确定。在这里，我们对 631 名肥胖受试者和 374 名正常体重对照的中国队列进行了鸟枪法宏基因组测序，并鉴定了肥胖受试者中富含的以巨单胞菌为主的肠型样簇。在这个队列中，巨型单胞菌和多基因风险的存在对肥胖表现出附加影响。鲁佩尔巨型单胞菌拥有肌醇降解基因，体外和体内均证明，添加肌醇可有效抑制肠道类器官中的脂肪酸吸收。此外，异源表达肌醇降解 iolG 基因的鲁佩尔分枝杆菌或大肠杆菌定植的小鼠表现出肠道脂质吸收增强，从而导致肥胖。总而言之，我们的研究结果揭示了 M. rupellensis 作为肌醇降解剂的作用，可增强脂质吸收和肥胖，为未来肥胖管理提出潜在策略。版权所有 © 2024 Elsevier Inc. 保留所有权利。

Numerous studies have reported critical roles for the gut microbiota in obesity. However, the specific microbes that causally contribute to obesity and the underlying mechanisms remain undetermined. Here, we conducted shotgun metagenomic sequencing in a Chinese cohort of 631 obese subjects and 374 normal-weight controls and identified a Megamonas-dominated, enterotype-like cluster enriched in obese subjects. Among this cohort, the presence of Megamonas and polygenic risk exhibited an additive impact on obesity. Megamonas rupellensis possessed genes for myo-inositol degradation, as demonstrated in vitro and in vivo, and the addition of myo-inositol effectively inhibited fatty acid absorption in intestinal organoids. Furthermore, mice colonized with M. rupellensis or E. coli heterologously expressing the myo-inositol-degrading iolG gene exhibited enhanced intestinal lipid absorption, thereby leading to obesity. Altogether, our findings uncover roles for M. rupellensis as a myo-inositol degrader that enhances lipid absorption and obesity, suggesting potential strategies for future obesity management.Copyright © 2024 Elsevier Inc. All rights reserved.