The chemical interactome space between the human host and the genetically defined gut metabotypes
Open accessAbstract
The bacteria that colonize the gastrointestinal tracts of mammals represent a highly selected microbiome that has a profound influence on human physiology by shaping the host’s metabolic and immune system activity. Despite the recent advances on the biological principles that underlie microbial symbiosis in the gut of mammals, mechanistic understanding of the contributions of the gut microbiome and how variations in the metabotypes are linked to the host health are obscure. Here, we mapped the entire metabolic potential of the gut microbiome based solely on metagenomics sequencing data derived from fecal samples of 124 Europeans (healthy, obese and with inflammatory bowel disease). Interestingly, three distinct clusters of individuals with high, medium and low metabolic potential were observed. By illustrating these results in the context of bacterial population, we concluded that the abundance of the Prevotella genera is a key factor indicating a low metabolic potential. These metagenome-based metabolic signatures were used to study the interaction networks between bacteria-specific metabolites and human proteins. We found that thirty-three such metabolites interact with disease-relevant protein complexes several of which are highly expressed in cells and tissues involved in the signaling and shaping of the adaptive immune system and associated with squamous cell carcinoma and bladder cancer. From this set of metabolites, eighteen are present in DrugBank providing evidence that we carry a natural pharmacy in our guts. Furthermore, we established connections between the systemic effects of non-antibiotic drugs and the gut microbiome of relevance to drug side effects and health-care solutions.
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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 [7]
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- Authors
- Jacobsen, U. P., Nielsen, H. B., Hildebrand, F., Raes, J., Sicheritz-Ponten, T., Kouskoumvekaki, I., & Panagiotou, G.
- Affiliations
- Technical University of Denmark (DK)
- Vrije Universiteit Brussel (BE)
- Center for Biological Sequence Analysis, Department of Systems Biology, Technical University of Denmark , Lyngby, Denmark
- University of Hong Kong (HK)
- Corresponding author
- Kouskoumvekaki, Irene
- Panagiotou, Gianni
- ORCID
- Venue
- The ISME Journal
- Publisher
- Oxford University Press (OUP)
- Published
- 2012-11-22
- Volume
- 7
- Issue
- 4
- Pages
- 730-742
- ISSN
- 1751-7362 (ISSN-L)
- 1751-7370
- PMC
- PMC3603391
- OpenAlex
- W1985762104
- Cited by
- 24
- References
- 50
- Citations by year
- 2023: 3 · 2022: 2 · 2021: 1 · 2020: 3 · 2018: 2 · 2017: 2 · 2016: 2 · 2015: 2 · 2014: 5 · 2013: 2
- FWCI
- 1.16
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- The ISME Journal (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- The HKU Scholars Hub (University of Hong Kong) (submittedVersion)
- Technical University of Denmark, DTU Orbit (Technical University of Denmark, DTU) (submittedVersion)
- VUBIR (Vrije Universiteit Brussel) (submittedVersion)
- Funders
- Novo Nordisk
- Novo Nordisk Fonden (NNF10CC1016517)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Dentistry › Periodontics › Oral microbiology and periodontitis research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Nutrition, Genetics, and Disease
- Keywords
- gut microbiota, host-microbe interactions, bacterial metabolites, human protein complex, Prevotella, obesity, inflammatory bowel disease, adaptive immunity, squamous cell carcinoma, bladder cancer, adverse drug reactions, non-antibiotic drugs
- MeSH terms
- Bacteria, Pharmaceutical Preparations, Feces, Humans, Obesity, Symbiosis, Inflammatory Bowel Diseases, Gastrointestinal Tract, Metagenome, Metabolome, Metagenomics
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