Gut Microbiota, Short Chain Fatty Acids, and Adiposity Across The Epidemiological Transition

The objective of this study is to define associations between gut microbiota, short chain
fatty acids (SCFAs) and obesity in populations spanning the epidemiologic transition, and
explore mechanisms by which these factors may independently and collectively influence the
development of obesity. The gut microbiota and SCFAs have been associated with obesity, yet
the causal mechanisms are unknown, as are the individual obesogenic effects of the individual
SCFAs (butyrate, acetate and propionate). Existing studies are, limited by contradictory
findings, small sample sizes, limited and imprecise measurements of obesity, and lack of
detailed dietary and other environmental exposures/mediators. The investigators propose to
overcome these challenges by leveraging an existing cohort of five diverse, well-defined
populations from the Modeling the Epidemiologic Transition Study (METS, R01-DK080763). METS
is comprised of a cohort of 2,500 African-origin adults, living in 5 distinctly different
environments; Ghana, South Africa, Jamaica, the Seychelles and the US, and who have been
prospectively followed since 2010. Our preliminary data suggest that while gut microbiota and
SCFAs differences exist across sites, similar relationships exist across the sites for gut
microbiota/SCFAs adiposity effects. In addition to yearly health measurements; the
investigators propose to measure gut microbiota and stool SCFAs in all participants (2500)
during the first year of the current study, thus providing one of the largest gut microbiota
population-based studies to date. We will divide our cohort of 2500 individuals into 2 sets:
(1) a test set of 1000 participants to explore which gut microorganisms and stool SCFAs are
associated with adiposity; (2) a validation set of 1500 participants to independently verify
the biomarkers identified in the test set, thus minimizing spurious correlations due to large
number of features (e.g., bacterial taxa). The investigators will follow all 2500
participants for 3 years to assess weight and adiposity changes, using Bayesian Kernel
Machine Regression modeling to explore whether changes can be predicted by gut microbiota and
SCFAs factors. Finally, using a causal mediation analysis, the investigators will identify
the direct and indirect effect of single and/or cumulative gut microbiota on adiposity as
mediated by SCFA. The investigators will thus capitalize upon an existing, extensively well
described cohort of adults of African-origin, with significant variability as a result of the
widespread geographic distributions, and therefore variation in the environmental covariate
exposures. The proposed study will substantially advance the understanding of the role gut
microbiota and SCFAs play in the development of obesity and provide novel obesity therapeutic
targets targeting SCFAs producing features of the gut microbiota.

Inclusion Criteria:

- Identify as African American or Black

- Age 18-50

Exclusion Criteria:

- Pregnancy, nursing, or planning to become pregnant

- Movement disorders or other disability that limits mobility