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.)).
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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.
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Liu, R., Hong, J., Xu, X. et al. Gut microbiome and serum metabolome alterations in obesity and after weight-loss intervention. Nat Med 23, 859–868 (2017). https://doi.org/10.1038/nm.4358
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DOI: https://doi.org/10.1038/nm.4358
