8513 Toxic Metals Are Associated With Increased Diabetes And Obesity Through Gut Microbiota Changes In Five African-Origin Populations

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Abstract Disclosure: J. Jorgensen: None. C. Choo-Kang: None. L. Issa: None. J.A. Gilbert: None. G. Ecklu-Mensah: None. A. Luke: None. K. Bedu-Addo: None. T. Forrester: None. P. Bovet: None. E.V. Lambert: None. D. Rae: None. M. Argos: None. Y. Dai: None. R.M. Sargis: None. L.R. Dugas: None. B.T. Layden: None. Obesity is associated with an increased risk for cardiometabolic diseases, such as type 2 diabetes mellitus (T2D). Prior research has shown an association between toxic metals/metalloid (hereafter, “metals”) exposures, including arsenic (As), lead (Pb), mercury (Hg), and cadmium (Cd), and increased T2D risk. Importantly, metal exposure has been suggested to impact the gut microbiome. Gut microbiome composition and metabolism are key to the development and progression of obesity and diabetes, thus we propose a potential novel interaction via the gut microbiota between metals and T2D, although the exact pathway remains unclear. We studied a large African-origin cohort from Ghana, South Africa, Jamaica, Seychelles, and the US (n=188, 51% female, mean age=43.0±6.5 yr). Analyzing 16S rRNA Amplicon sequencing, anthropometrics, and creatinine-adjusted urinary metal levels, we observed metal levels were significantly associated with country of origin and in most countries were significantly associated with decreased microbial diversity. Metal levels were highest in Ghana and lowest in the US, and were significantly different between Ghana and the US for As and Pb (p-value < 2.2e-16). Individually, Pb levels were significantly associated with fasting blood glucose and BMI, As levels were associated with T2D diagnosis, and Hg levels were associated with obesity diagnosis. Pb levels were significantly associated with a lower proportion of potential acetate- and butyrate-producing microbial strains. Similarly, As levels were associated with decreased proportion of potential butyrate-producing genera. Microbial strains in individuals with high Pb levels showed significant association with obesity and T2D risk and strains in individuals with significant high As levels were associated with only T2D risk. Hg and Cd were not significantly associated with microbes and clinical status. These taxa are significantly associated with increased heme metabolism. With this study, we aimed to begin to describe the effect of metals and the risks for obesity and diabetes through its action within the gut microbiome. We demonstrate that toxic metal exposures were associated with differences in the gut microbiome and predicted metabolism that may also be associated with increased obesity and T2D risk. Presentation: 6/1/2024

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