Population study of the gut microbiome: associations with diet, lifestyle, and cardiometabolic disease
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13073_2021_Article_1007.pdf
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14.5 MB
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Unknown
Checksum (MD5)
bb842c61e1c461dbce5e8d4c1ef94cdb
Author(s)
Walker, Rebecca L.
Vlamakis, Hera
Lee, Jonathan W. J.
Besse, Luke A.
Xanthakis, Vanessa
Vasan, Ramachandran S.
Shaw, Stanley Y
Xavier, Ramnik Joseph
Date Issued
December 17, 2021
Publisher
BioMed Central
Citation
Genome Medicine. 2021 Dec 17;13(1):188
Version
Final published version
Abstract
Abstract
Background
The human gut harbors trillions of microbes that play dynamic roles in health. While the microbiome contributes to many cardiometabolic traits by modulating host inflammation and metabolism, there is an incomplete understanding regarding the extent that and mechanisms by which individual microbes impact risk and development of cardiovascular disease (CVD). The Framingham Heart Study (FHS) is a multi-generational observational study following participants over decades to identify risk factors for CVD by correlating genetic and phenotypic factors with clinical outcomes. As a large-scale population-based cohort with extensive clinical phenotyping, FHS provides a rich landscape to explore the relationships between the gut microbiome and cardiometabolic traits.
Methods
We performed 16S rRNA gene sequencing on stool from 1423 participants of the FHS Generation 3, OMNI2, and New Offspring Spouse cohorts. Data processing and taxonomic assignment were performed with the 16S bioBakery workflow using the UPARSE pipeline. We conducted statistical analyses to investigate trends in overall microbiome composition and diversity in relation to disease states and systematically examined taxonomic associations with a variety of clinical traits, disease phenotypes, clinical blood markers, and medications.
Results
We demonstrate that overall microbial diversity decreases with increasing 10-year CVD risk and body mass index measures. We link lifestyle factors, especially diet and exercise, to microbial diversity. Our association analyses reveal both known and unreported microbial associations with CVD and diabetes, related prescription medications, as well as many anthropometric and blood test measurements. In particular, we observe a set of microbial species that demonstrate significant associations with CVD risk, metabolic syndrome, and type 2 diabetes as well as a number of shared associations between microbial species and cardiometabolic subphenotypes.
Conclusions
The identification of significant microbial taxa associated with prevalent CVD and diabetes, as well as risk for developing CVD, adds to increasing evidence that the microbiome may contribute to CVD pathogenesis. Our findings support new hypothesis generation around shared microbe-mediated mechanisms that influence metabolic syndrome, diabetes, and CVD risk. Further investigation of the gut microbiomes of CVD patients in a targeted manner may elucidate microbial mechanisms with diagnostic and therapeutic implications.
MIT Department
Massachusetts Institute of Technology. Center for Microbiome Informatics and Therapeutics
Klarman Cell Observatory (Broad Institute)
Broad Institute of MIT and Harvard
Terms of Use
Creative Commons Attribution
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1186/s13073-021-01007-5
