Symbiotic gut microbes modulate human metabolic phenotypes
Open accessAbstract
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.
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Humans and microbes have coevolved over millions of years, contributing to the interdependency of host and microbiota physiological activities.
“Humans and microbes have coevolved over millions of years, thereby contributing to the interdependency of host and microbiota physiological activities.1”
From Regulation of Intestinal Barrier Function by Microbial Metabolites (2021) · cites this paper as [1]
The gut microbiome can be viewed as an anaerobic bioreactor programmed to synthesize molecules that direct the mammalian immune system, modify the mammalian epigenome, and regulate host metabolism.
“the gut microbiome can be viewed as an anaerobic bioreactor programmed to synthesize molecules which direct the mammalian immune system,5 modify the mammalian epigenome,6 and regulate host metabolism.7”
From The Gut Microbiome and the Brain (2014) · cites this paper as [6]
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- Authors
- 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., Yang, S., Holmes, E., Tang, H., Zhao, G., Nicholson, J. K., Li, L., & Zhao, L.
- Affiliations
- Shanghai Jiao Tong University (CN)
- First Affiliated Hospital Zhejiang University (CN)
- Imperial College London (GB)
- Chinese National Human Genome Center (CN)
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University, Hangzhou 310003, China;
- Chinese Academy of Sciences (CN)
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2008-02-12
- Volume
- 105
- Issue
- 6
- Pages
- 2117-2122
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC2538887
- OpenAlex
- W2152805980
- Cited by
- 1,144
- References
- 42
- Citations by year
- 2026: 14 · 2025: 23 · 2024: 51 · 2023: 51 · 2022: 49 · 2021: 78 · 2020: 69 · 2019: 68 · 2018: 65 · 2017: 89 · 2016: 60 · 2015: 60 · 2014: 73 · 2013: 76 · 2012: 69
- FWCI
- 33.97
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolomics and Mass Spectrometry Studies
- Health Sciences › Dentistry › Periodontics › Oral microbiology and periodontitis research
- Keywords
- gut microbiota, human-microbe interactions, metabolic phenotypes, functional metagenomics, Faecalibacterium prausnitzii, urinary metabolites, fecal metabolites, Chinese population, drug metabolism
- MeSH terms
- Bacteria, Electrophoresis, Polyacrylamide Gel, Humans, Intestines, Metabolism, Molecular Sequence Data, Magnetic Resonance Spectroscopy, Phenotype, Phylogeny, Symbiosis
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