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Butyrate-Producing Bacteria and Insulin Homeostasis: The Microbiome and Insulin Longitudinal Evaluation Study (MILES)

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posted on 2022-08-12, 15:58 authored by Jinrui Cui, Gautam Ramesh, Martin Wu, Elizabeth T. Jensen, Osa Crago, Alain G. Bertoni, Chunxu Gao, Kristi L. Hoffman, Patricia A. Sheridan, Kari E. Wong, Alexis C. Wood, Yii-Der I. Chen, Jerome I. Rotter, Joseph F. Petrosino, Stephen S. Rich, Mark O. Goodarzi

Gut microbiome studies have documented depletion of butyrate-producing taxa in type 2 diabetes. We analyzed associations between butyrate-producing taxa and detailed measures of insulin homeostasis whose dysfunction underlies diabetes in 224 non-Hispanic Whites and 129 African Americans, all of whom completed an oral glucose tolerance test. Stool microbiome was assessed by whole metagenome shotgun sequencing with taxonomic profiling. We examined associations between 36 butyrate-producing taxa (7 genera, 29 species) and insulin sensitivity, insulin secretion, disposition index, insulin clearance, and prevalence of dysglycemia (prediabetes plus diabetes, 46% of cohort), adjusting for age, sex, body mass index, and race. Genus Coprococcus was associated with higher insulin sensitivity (β=0.14, P=0.002) and disposition index (β=0.12, P=0.012) and a lower rate of dysglycemia (odds ratio 0.91, 95% confidence interval (CI) 0.85-0.97, P=0.0025); in contrast, Flavonifractor was associated with lower insulin sensitivity (β=-0.13, P=0.004) and disposition index (β=-0.11, P=0.04) and higher prevalence of dysglycemia (OR 1.22, 95% CI 1.08-1.38, P=0.0013). Species-level analyses found 10 bacteria associated with beneficial directions of effects and two bacteria with adverse associations on insulin homeostasis and dysglycemia. While most butyrate-producers analyzed appear to be metabolically beneficial, this is not the case for all such bacteria, suggesting that microbiome-directed therapeutic measures to prevent or treat diabetes should be targeted to specific butyrate-producing taxa rather than all butyrate producers.

Funding

This study was supported in part by National Institutes of Health grants from the National Institute of Diabetes and Digestive and Kidney Disease (R01-DK109588, P30-DK063491) and from the National Center for Advancing Translational Sciences (UL1TR001420, UL1TR001881). M.O.G. was supported by the Eris M. Field Chair in Diabetes Research. A.C.W. was supported, in part, by USDA/ARS cooperative agreement # 58-3092-5-001. The contents of this publication do not necessarily reflect the views or policies of the U.S. Department of Agriculture, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government.

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