Symbiotic gut microbes modulate human metabolic phenotypes

Min Li, Baohong Wang, Menghui Zhang, Mattias Rantalainen, Shengyue Wang, Haokui Zhou, Yan Zhang, Jian Shen, Xiaoyan Pang, Meiling Zhang, Hua Wei, Yu Chen, Haifeng Lu, Jian Zuo, Mingming Su, Yunping Qiu, Wei Jia, Chaoni Xiao, Leon M. Smith, Shengli YangElaine Holmes, Huiru Tang, Guoping Zhao, Jeremy K. Nicholson, Lanjuan Li, Liping Zhao

Research output: Contribution to journalArticle

700 Scopus citations

Abstract

Humans have evolved intimate symbiotic relationships with a consortium of gut microbes (microbiome) and individual variations in the microbiome influence host health, may be implicated in disease etiology, and affect drug metabolism, toxicity, and efficacy. However, the molecular basis of these microbe-host interactions and the roles of individual bacterial species are obscure. We now demonstrate a"transgenomic" approach to link gut microbiome and metabolic phenotype (metabotype) variation. We have used a combination of spectroscopic, microbiomic, and multivariate statistical tools to analyze fecal and urinary samples from seven Chinese individuals (sampled twice) and to model the microbial-host metabolic connectivities. At the species level, we found structural differences in the Chinese family gut microbiomes and those reported for American volunteers, which is consistent with population microbial cometabolic differences reported in epidemiological studies. We also introduce the concept of functional metagenomics, defined as "the characterization of key functional members of the microbiome that most influence host metabolism and hence health." For example, Faecalibacterium prausnitzii population variation is associated with modulation of eight urinary metabolites of diverse structure, indicating that this species is a highly functionally active member of the microbiome, influencing numerous host pathways. Other species were identified showing different and varied metabolic interactions. Our approach for understanding the dynamic basis of host-microbiome symbiosis provides a foundation for the development of functional metagenomics as a probe of systemic effects of drugs and diet that are of relevance to personal and public health care solutions.

Original languageEnglish (US)
Pages (from-to)2117-2122
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume105
Issue number6
DOIs
StatePublished - Feb 12 2008

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Keywords

  • Covariation analysis
  • Gut microbiota
  • Metabonomics
  • Metabotype
  • Metagenomics

ASJC Scopus subject areas

  • General

Cite this

Li, M., Wang, B., Zhang, M., Rantalainen, M., Wang, S., Zhou, H., Zhang, Y., Shen, J., Pang, X., Zhang, M., Wei, H., Chen, Y., Lu, H., Zuo, J., Su, M., Qiu, Y., Jia, W., Xiao, C., Smith, L. M., ... Zhao, L. (2008). Symbiotic gut microbes modulate human metabolic phenotypes. Proceedings of the National Academy of Sciences of the United States of America, 105(6), 2117-2122. https://doi.org/10.1073/pnas.0712038105