Extensive transmission of microbes along the gastrointestinal tract
- European Molecular Biology Laboratory, Germany
- Université Paris-Est, France
- University of Luxembourg, Luxembourg
Abstract
The gastrointestinal tract is abundantly colonized by microbes, yet the translocation of oral species to the intestine is considered a rare aberrant event, and a hallmark of disease. By studying salivary and fecal microbial strain populations of 310 species in 470 individuals from five countries, we found that transmission to, and subsequent colonization of, the large intestine by oral microbes is common and extensive among healthy individuals. We found evidence for a vast majority of oral species to be transferable, with increased levels of transmission in colorectal cancer and rheumatoid arthritis patients and, more generally, for species described as opportunistic pathogens. This establishes the oral cavity as an endogenous reservoir for gut microbial strains, and oral-fecal transmission as an important process that shapes the gastrointestinal microbiome in health and disease.
Data availability
Raw sequencing data have been deposited in the European Nucleotide Archive under project accessions PRJNA289586 and PRJEB28422.
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The Salivary Microbiome in Health and DiseaseEuropean Nucleotide Archive, PRJEB28422.
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Human Gut Microbiome in a Multiplex Family Study of Type 1 Diabetes MellitusEuropean Nucleotide Archive, PRJNA289586.
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The oral and gut microbiomes are perturbed in rheumatoid arthritis and partly normalized after treatment.European Nucleotide Archive, PRJEB6997.
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FijiCOMP: saliva and stool metagenomesEuropean Nucleotide Archive, PRJNA217052.
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Temporal and technical variability of human gut metagenomes.European Nucleotide Archive, PRJEB8347.
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Potential of fecal microbiota for early-stage detection of colorectal cancer.European Nucleotide Archive, PRJEB6070.
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Integrated multi-omics of the human gut microbiome in a case study of familial type 1 diabetes.European Nucleotide Archive, PRJNA289586.
Article and author information
Author details
Thomas Sebastian Benedikt Schmidt
Carine de Beaufort
Anna Heintz-Buschart
Funding
Fonds National de la Recherche Luxembourg (CORE/15/BM/10404093)
- Thomas Sebastian Benedikt Schmidt
- Matthew Robert Hayward
- Anna Heintz-Buschart
H2020 European Research Council (ERC-AdG-669830)
- Thomas Sebastian Benedikt Schmidt
- Simone S Li
- Oleksandr M Maistrenko
- Renato JC Alves
- Peer Bork
H2020 Marie Skłodowska-Curie Actions (661019)
- Matthew Robert Hayward
German Network Bioinformatics (de.NBI #031A537B)
- Georg Zeller
- Peer Bork
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Human subjects: Informed consent was obtained from all study subjects for which novel data was generated; see respective previous publications for details (PMID: 27723761; PMID: 25432777; PMID: 25888008).
Copyright
© 2019, Schmidt et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Extensive transmission of microbes along the gastrointestinal tract
eLife 8:e42693.
https://doi.org/10.7554/eLife.42693
Further reading
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- Microbiology and Infectious Disease
eLife is pleased to present a Special Issue to highlight recent advances in the mechanistic understanding of microbiome function.
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- Computational and Systems Biology
- Genetics and Genomics
Obesity is a major risk factor for type 2 diabetes, dyslipidemia, cardiovascular disease, and hypertension. Intriguingly, there is a subset of metabolically healthy obese (MHO) individuals who are seemingly able to maintain a healthy metabolic profile free of metabolic syndrome. The molecular underpinnings of MHO, however, are not well understood. Here, we report that CTRP10/C1QL2-deficient mice represent a unique female model of MHO. CTRP10 modulates weight gain in a striking and sexually dimorphic manner. Female, but not male, mice lacking CTRP10 develop obesity with age on a low-fat diet while maintaining an otherwise healthy metabolic profile. When fed an obesogenic diet, female Ctrp10 knockout (KO) mice show rapid weight gain. Despite pronounced obesity, Ctrp10 KO female mice do not develop steatosis, dyslipidemia, glucose intolerance, insulin resistance, oxidative stress, or low-grade inflammation. Obesity is largely uncoupled from metabolic dysregulation in female KO mice. Multi-tissue transcriptomic analyses highlighted gene expression changes and pathways associated with insulin-sensitive obesity. Transcriptional correlation of the differentially expressed gene (DEG) orthologs in humans also shows sex differences in gene connectivity within and across metabolic tissues, underscoring the conserved sex-dependent function of CTRP10. Collectively, our findings suggest that CTRP10 negatively regulates body weight in females, and that loss of CTRP10 results in benign obesity with largely preserved insulin sensitivity and metabolic health. This female MHO mouse model is valuable for understanding sex-biased mechanisms that uncouple obesity from metabolic dysfunction.
