Abstract
BackgroundWhile some of the variance observed in adiposity and weight change within populations can be accounted for by traditional risk factors, a new factor, the gut microbiota, has recently been associated with obesity. However, the causal mechanisms through which the gut microbiota and its metabolites, short chain fatty acids (SCFAs) influence obesity are unknown, as are the individual obesogenic effects of the individual SCFAs (butyrate, acetate and propionate). This study, METS-Microbiome, proposes to examine the influence of novel risk factors, the gut microbiota and SCFAs, on obesity, adiposity and weight change in an international established cohort spanning the epidemiologic transition.MethodsThe parent study; Modeling the Epidemiologic Transition Study (METS) is a well-established and ongoing prospective cohort study designed to assess the association between body composition, physical activity, and relative weight, weight gain and cardiometabolic disease risk in five diverse population-based samples in 2500 people of African descent. The cohort has been prospectively followed since 2009. Annual measures of obesity risk factors, including body composition, objectively measured physical activity and dietary intake, components which vary across the spectrum of social and economic development. In our new study; METS-Microbiome, in addition to continuing yearly measures of obesity risk, we will also measure gut microbiota and stool SCFAs in all contactable participants, and follow participants for a further 3 years, thus providing one of the largest gut microbiota population-based studies to date.DiscussionThis new study capitalizes 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 METS-Microbiome 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.Trial registrationRegistered NCT03378765 Date first posted: December 20, 2017.
Highlights
While some of the variance observed in adiposity and weight change within populations can be accounted for by traditional risk factors, a new factor, the gut microbiota, has recently been associated with obesity
While some of the variance observed in obesity within populations can be accounted for by traditional risk factors such as total energy expenditure, physical activity (PA) level, dietary intake, genetics, socioeconomic status or education level [1,2,3,4,5,6], a new factor, the gut microbiota have been recently implicated in obesity [7,8,9]
The Modeling the Epidemiologic Transition Study (METS)-Microbiome study will substantially advance the understanding of the role gut microbiota and short chain fatty acids (SCFAs) play in the development of obesity and provide novel obesity therapeutic targets targeting SCFAs producing features of the gut microbiota
Summary
Design and settings The parent study; METS, is a well-established and ongoing prospective cohort study designed to assess the association between body composition, PA, and relative weight, weight gain and cardiometabolic disease risk in five diverse population-based samples of African descent (NIH R01-DK080763). Bioinformatics data analysis We will perform a Microbiome Wide Association Study (MWAS; [86]) to determine whether fecal microbial biomarkers are predictive of participant variables. Univariate and bivariate summary statistics and distributional plots will be examined for all variables and Covariates of interest Based on biological considerations, it will be important to consider the following variables, among others, as covariates of interest in our analyses: age, sex, site, BMI, family or previous history of diabetes or currently taking medications for diabetes or hypertension, blood pressure, nutritional status indicators (e.g., dietary nutrient and specific food intakes), smoking, alcohol use, education, occupation and employment status, marital status, parity (females) and physical activity
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