FRI010 Human Gut Microbiota And Metabolic Profiles Are Associated With Obesity In Five African-Origin Populations
Authors: Jorgensen Julianne , Choo-Kang Candice , Ecklu-Mensah Gertrude , Gilbert Jack , Luke Amy , Bedu-Addo Kweku , Forrester Terrence E , Bovet Pascal , Lambert Estelle V , Rae Dale , Dugas Lara , Dai Yang , Layden Brian T 
Published: October 2023

Abstract
Disclosure: J. Jorgensen: None. C. Choo-Kang: None. G. Ecklu-Mensah: None. J. Gilbert: None. A. Luke: None. K. Bedu-Addo: None. T.E. Forrester: None. P. Bovet: None. E.V. Lambert: None. D. Rae: None. L. Dugas: None. Y. Dai: None. B.T. Layden: None.
Obesity is a global public health crisis, which since 1975 has tripled world-wide. Concomitantly, obesity-related conditions such as cardiovascular disease, stroke, and type 2 diabetes have also increased. An accepted common obesogenic factor has been a shift away from fiber-rich diets to ultra-processed foods. Fiber is digested by the gut microbiota, resulting in the production of short-chain fatty acids (SCFAs), and diets that are rich in fiber are associated with greater microbial diversity and increased serum and fecal SCFA levels. Yet, the mechanistic link between dietary fiber and improved metabolic outcomes, via SCFAs, is not clearly defined. We analyzed data from a large ongoing prospective study of African-origin adults from 5 countries (Ghana, South Africa, Jamaica, Seychelles & US), each with distinct dietary fiber intakes. Standard methods were used to assess taxonomy, Shannon alpha diversity and beta diversity, as well as taxonomic differences by fecal SCFA levels as a proxy for fiber intake. Thereafter, microbiota taxa were used to predict functional metabolite profiles, as well as the metabolic pathway abundances to identify differential metabolites correlated with SCFA levels. These profiles and pathways were correlated with SCFA levels within and between sites. As microbes interact and impact each other, we constructed differential microbial co-occurrence networks to identify hub species and differences in community configuration across sites comparing SCFA levels via Network Construction and comparison for Microbiome data (NetCoMi). The final sample included 1904 participants (age=42.57±8.04 yr). The mean BMI was lowest in Ghana (BMI=26.72±5.88 kg/m2), and highest in the US (BMI=34.42±9.06 kg/m2) with a p-value &lt; 2.2e-16. Conversely, diets in Ghana had the highest fiber intake resulting in the highest fecal SCFA levels (8026.97±2605.38 µg/g) which was significantly greater than US SCFA levels (p-value &lt; 2e-16). Not surprisingly, differences in microbial diversity were unique to each site as well as adiposity levels. Overall, non-obese individuals had a higher proportion of Prevotella, Allaprevotella compared to obese individuals who had higher proportions of Firmicutes. Prevotella and Allaprevotella are known SCFAs producers and previously shown to be anti-inflammatory in the gut, while Firmicutes are positively correlated with gut inflammation. We provide evidence that fiber-rich diets may act through the anti-inflammatory pathways associated with the gut microbiota in humans. Future research should elucidate the gut microbial mediated anti-inflammatory effects and the metabolic pathways to develop novel anti-inflammatory therapeutics.
Presentation: Friday, June 16, 2023