Gut microbiota, short chain fatty acids, and obesity across the epidemiologic transition: the METS-Microbiome study protocol

Lara R Dugas, Louise Lie, Jacob Plange-Rhule, Kweku Bedu-Addo, Pascal Bovet, Estelle V Lambert, Terrence E Forrester, Amy Luke, Jack A Gilbert, Brian T Layden, Lara R Dugas, Louise Lie, Jacob Plange-Rhule, Kweku Bedu-Addo, Pascal Bovet, Estelle V Lambert, Terrence E Forrester, Amy Luke, Jack A Gilbert, Brian T Layden

Abstract

Background: 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. 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.

Methods: The 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.

Discussion: This 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 registration: Registered NCT03378765 Date first posted: December 20, 2017.

Keywords: Epidemiologic transition; Gut microbiota; Obesity; Short chain fatty acids.

Conflict of interest statement

The protocol for METS-Microbiome was approved by the Institutional Review Board of Loyola University Chicago, IL, USA. Approval granted under LU209537. All site protocols have been approved by the local participating institutions; specifically by the Committee on Human Research Publication and Ethics of Kwame Nkrumah University of Science and Technology, Kumasi, Ghana; the Research Ethics Committee of the University of Cape Town, South Africa; the Board for Ethics and Clinical Research of the University of Lausanne, Switzerland; the Health Research and Ethic Committee of the Ministry of Health of Seychelles, and the Ethics Committee of the University of the West Indies, Kingston, Jamaica.

Not applicable.

The authors declare that they have no competing interests.

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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