Abstract：
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.
摘要：
许多研究报道了肠道微生物群在肥胖中的关键作用。然而,导致肥胖的特定微生物及其潜在机制仍未确定。这里,我们在631名肥胖受试者和374名正常体重对照的中国队列中进行了鸟枪宏基因组测序，并确定了以Megamonas为主的，富含肥胖受试者的肠型样簇。在这个群体中，Megamonas的存在和多基因风险对肥胖有累加影响.rupellensis拥有肌醇降解的基因，如体外和体内所证明的，肌醇的添加有效抑制了肠道类器官中脂肪酸的吸收。此外，用M.rupellensis或大肠杆菌异源表达肌醇降解iolG基因的小鼠表现出增强的肠道脂质吸收，从而导致肥胖。总之,我们的发现揭示了M.rupellensis作为一种促进脂质吸收和肥胖的肌醇降解剂的作用，提出未来肥胖管理的潜在策略。
