2. Academic Validation
  3. Obesity-enriched gut microbe degrades myo-inositol and promotes lipid absorption

Obesity-enriched gut microbe degrades myo-inositol and promotes lipid absorption

  • Cell Host Microbe. 2024 Jul 9:S1931-3128(24)00230-0. doi: 10.1016/j.chom.2024.06.012.
Chao Wu 1,  Fangming Yang 2,  Huanzi Zhong 2,  Jie Hong 1,  Huibin Lin 1,  Mingxi Zong 1,  Huahui Ren 2,  Shaoqian Zhao 1,  Yufei Chen 1,  Zhun Shi 2,  Xingyu Wang 1,  Juan Shen 3,  Qiaoling Wang 1,  Mengshan Ni 1,  Banru Chen 1,  Zhongle Cai 1,  Minchun Zhang 1,  Zhiwen Cao 1,  Kui Wu 4,  Aibo Gao 1,  Junhua Li 3,  Cong Liu 3,  Minfeng Xiao 3,  Yan Li 3,  Juan Shi 1,  Yifei Zhang 1,  Xun Xu 3,  Weiqiong Gu 1,  Yufang Bi 1,  Guang Ning 5,  Weiqing Wang 6,  Jiqiu Wang 7,  Ruixin Liu 8
Affiliations

Affiliations

  • 1 Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai Key Laboratory for Endocrine Tumor, State Key Laboratory of Medical Genomics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • 2 BGI Research, Shenzhen 518083, China; Institute of Intelligent Medical Research (IIMR), BGI Genomics, Shenzhen 518083, China.
  • 3 BGI Research, Shenzhen 518083, China.
  • 4 BGI Research, Shenzhen 518083, China; Institute of Intelligent Medical Research (IIMR), BGI Genomics, Shenzhen 518083, China; Guangdong Provincial Key Laboratory of Human Disease Genomics, Shenzhen Key Laboratory of Genomics, BGI Research, Shenzhen 518083, China.
  • 5 Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai Key Laboratory for Endocrine Tumor, State Key Laboratory of Medical Genomics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. Electronic address: gning@sibs.ac.cn.
  • 6 Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai Key Laboratory for Endocrine Tumor, State Key Laboratory of Medical Genomics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. Electronic address: wqingw@shsmu.edu.cn.
  • 7 Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai Key Laboratory for Endocrine Tumor, State Key Laboratory of Medical Genomics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. Electronic address: wangjq@shsmu.edu.cn.
  • 8 Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai Key Laboratory for Endocrine Tumor, State Key Laboratory of Medical Genomics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. Electronic address: xiner198287@163.com.
PMID: 38996548 DOI: 10.1016/j.chom.2024.06.012
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.

Keywords

Megamonas; Megamonas rupellensis; Obesity; enterotype; genetics; gut microbiome; lipid absorption; myo-inositol; obesogenic microbe; polygenic risk.

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