Abstract

Emerging evidence has linked the gut microbiome to human obesity. We performed a metagenome-wide association study and serum metabolomics profiling in a cohort of lean and obese, young, Chinese individuals. We identified obesity-associated gut microbial species linked to changes in circulating metabolites. The abundance of Bacteroides thetaiotaomicron, a glutamate-fermenting commensal, was markedly decreased in obese individuals and was inversely correlated with serum glutamate concentration. Consistently, gavage with B. thetaiotaomicron reduced plasma glutamate concentration and alleviated diet-induced body-weight gain and adiposity in mice. Furthermore, weight-loss intervention by bariatric surgery partially reversed obesity-associated microbial and metabolic alterations in obese individuals, including the decreased abundance of B. thetaiotaomicron and the elevated serum glutamate concentration. Our findings identify previously unknown links between intestinal microbiota alterations, circulating amino acids and obesity, suggesting that it may be possible to intervene in obesity by targeting the gut microbiota.

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Acknowledgements

The authors thank the field workers for their contribution and the participants for their cooperation. We thank H.B. Nielsen, S.B. Pedersen and H. Zhao for their contribution to data discussions. We thank P. Yin, S. Wang and H. Yu for their assistance in cultivating bacteria. This study was supported by grants from National Natural Science Foundation of China (no. 81621061 (G.N.), 81522011 (J.W.), 81370963 (R.L.), 81570758 (R.L.), 81370949 (J.W.), 81570757 (J.W.), 81471060 (J.H.) and 81670761 (Y.G.)), National International Science Cooperation Foundation (no. 2015DFA30560, W.W.), 973 Foundation (no. 2015CB553600, G.N.) and Shenzhen Municipal Government of China (no. JSGG20140702161403250 (Q.F.), DRC-SZ[2015]162 (Q.F.), JSGG20160229172752028 (J.L.) and JCYJ20160229172757249 (H.J.)).

Author information

Author notes

    • Ruixin Liu
    • , Jie Hong
    • , Xiaoqiang Xu
    • , Qiang Feng
    • , Dongya Zhang
    •  & Yanyun Gu

    These authors contributed equally to this work.

Affiliations

  1. State Key Laboratory of Medical Genomes, National Clinical Research Center for Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

    • Ruixin Liu
    • , Jie Hong
    • , Yanyun Gu
    • , Juan Shi
    • , Shaoqian Zhao
    • , Wen Liu
    • , Bin Cui
    • , Peiwen Liang
    • , Liuqing Xi
    • , Wanyu Li
    • , Rui Wang
    • , Yingkai Sun
    • , Minglan Yang
    • , Yuxin Shen
    • , Yifei Zhang
    • , Weiqiong Gu
    • , Yufang Bi
    • , Jiqiu Wang
    • , Guang Ning
    •  & Weiqing Wang
  2. BGI-Shenzhen, Shenzhen, China.

    • Xiaoqiang Xu
    • , Qiang Feng
    • , Dongya Zhang
    • , Xiaokai Wang
    • , Huihua Xia
    • , Zhipeng Liu
    • , Huijue Jia
    • , Zhou Lan
    • , Fengyu Li
    • , Zhuye Jie
    • , Junhua Li
    • , Xiaomin Chen
    • , Huanzi Zhong
    • , Hailiang Xie
    • , Xun Xu
    • , Huanming Yang
    • , Jian Wang
    • , Lise Madsen
    •  & Karsten Kristiansen
  3. BGI Education Center, University of Chinese Academy of Sciences, Shenzhen, China.

    • Xiaoqiang Xu
    •  & Xiaokai Wang
  4. Shenzhen Engineering Laboratory of Detection and Intervention of Human Intestinal Microbiome, BGI-Shenzhen, Shenzhen, China.

    • Qiang Feng
  5. China National GeneBank, BGI-Shenzhen, Shenzhen, China.

    • Huihua Xia
    • , Huijue Jia
    • , Zhuye Jie
    • , Junhua Li
    • , Huanzi Zhong
    • , Xun Xu
    •  & Karsten Kristiansen
  6. Laboratory of Endocrinology and Metabolism, Institute of Health Sciences, Shanghai Institutes for Biological Sciences (SIBS), Chinese Academy of Sciences (CAS) & Shanghai Jiao Tong University School of Medicine (SJTUSM), Shanghai, China.

    • Bin Cui
    •  & Guang Ning
  7. Pancreatic Disease Center, Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

    • Jiabin Jin
    • , Xiayang Ying
    • , Xiaxing Deng
    •  & Baiyong Shen
  8. CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, China.

    • Xiaolin Wang
    • , Xinjie Zhao
    •  & Guowang Xu
  9. Shenzhen Key Laboratory of Human Commensal Microorganisms and Health Research, BGI-Shenzhen, Shenzhen, China.

    • Huijue Jia
    •  & Junhua Li
  10. James D. Watson Institute of Genome Sciences, Hangzhou, China.

    • Huanming Yang
    •  & Jian Wang
  11. Department of Radiology and Radiological Science, Johns Hopkins School of Medicine, Baltimore, Maryland, USA.

    • Shenghan Lai
  12. Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts, USA.

    • Lu Qi
  13. Department of Epidemiology, School of Public Health and Tropical Medicine, Tulane University, New Orleans, Louisiana, USA.

    • Lu Qi
  14. National Institute of Nutrition and Seafood Research, Bergen, Norway.

    • Lise Madsen
  15. Laboratory of Genomics and Molecular Biomedicine, Department of Biology, University of Copenhagen, Copenhagen, Denmark.

    • Lise Madsen
    •  & Karsten Kristiansen

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Contributions

W.W., K.K. and G.N. conceived and designed the project. W.W., G.N. J.H., R.L., Y.G. and Jiqiu Wang managed the study. J.H., J.S., Y.G., Y.Z., W.G., B.S., X.D., J.J. and Y.B. made clinical diagnosis, recruited subjects and performed intervention. J.S., P.L., L.X., X.Y., Wanyu Li, R.W., Y. Shen, M.Y. and Y. Sun collected samples and clinical phenotypes. Xiaoqiang Xu, Q.F., D.Z., Xiaokai Wang., H. Xia, Z. Lan, Z.J., J.L., H.Z., and H. Xie performed bioinformatics analyses. Z. Liu, F.L. and X.C. performed metabolomics profiling and data analysis. Xiaolin Wang., X.Z. and G.X. performed targeted amino acid profiling. S.Z. and Wen Liu conducted animal experiments. R.L., K.K., W.W., G.N. and Jiqiu Wang wrote the manuscript. L.M., L.Q., S.L., B.C., H.J., Xun Xu, H.Y. and Jian Wang contributed to text revision and discussion.

Competing interests

The authors declare no competing financial interests.

Corresponding authors

Correspondence to Guang Ning or Karsten Kristiansen or Weiqing Wang.

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https://doi.org/10.1038/nm.4358

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