4.8 Article

The long-term genetic stability and individual specificity of the human gut microbiome

Journal

CELL
Volume 184, Issue 9, Pages 2302-+

Publisher

CELL PRESS
DOI: 10.1016/j.cell.2021.03.024

Keywords

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Funding

  1. Netherlands Heart Foundation (IN-CONTROL CVON) [2012-03, 2018-27]
  2. NWO Gravitation Exposome-NL [024.004.017]
  3. NWO-VIDI [864.13.013, 016.178.056, 016.136.308]
  4. NWO [SPI 92-266]
  5. European Research Council (ERC) FP7/2007-2013/ERC Advanced Grant [2012-322698]
  6. ERC [715772, 101001678]
  7. RuG Investment Agenda Grant Personalized Health
  8. Netherlands Organ-on-Chip Initiative, an NWO Gravitation project - Ministry of Education, Culture and Science of the government of the Netherlands [024.003.001]
  9. Foundation De Cock-Hadders grant [20:20-13]
  10. University Medical Center Groningen [CSC201708320268]
  11. China Scholarship Council [CSC201708320268, CSC201904910478]
  12. Graduate School of Medical Sciences, University of Groningen
  13. Junior Scientific Masterclass (JSM), University of Groningen
  14. Seerave Foundation
  15. Dutch Digestive Foundation [16-14]
  16. European Research Council (ERC) [101001678] Funding Source: European Research Council (ERC)

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By tracking the gut microbiome, human phenotypes, and metabolites, researchers have developed a microbial fingerprinting method for classifying samples with high accuracy. The study suggests that the gut microbiome may influence cardiometabolic health through its metabolites, highlighting the importance of microbial stability and variation in relation to host physiology.
By following up the gut microbiome, 51 human phenotypes and plasma levels of 1,183 metabolites in 338 individuals after 4 years, we characterize microbial stability and variation in relation to host physiology. Using these individual-specific and temporally stable microbial profiles, including bacterial SNPs and structural variations, we develop a microbial fingerprinting method that shows up to 85% accuracy in classifying meta-genomic samples taken 4 years apart. Application of our fingerprinting method to the independent HMP cohort results in 95% accuracy for samples taken 1 year apart. We further observe temporal changes in the abundance of multiple bacterial species, metabolic pathways, and structural variation, as well as strain replacement. We report 190 longitudinal microbial associations with host phenotypes and 519 associations with plasma metabolites. These associations are enriched for cardiometabolic traits, vitamin B, and uremic toxins. Finally, mediation analysis suggests that the gut microbiome may influence cardiometabolic health through its metabolites.

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