학술논문

79-OR: Butyrate Producing Bacteria and Insulin Homeostasis: The Microbiome and Insulin Longitudinal Evaluation Study (MILES).
Document Type
Article
Source
Diabetes. 2021 Supplement 1, Vol. 70, pN.PAG-N.PAG. 1p.
Subject
Language
ISSN
0012-1797
Abstract
Several studies have compared the stool microbiomes of people with and without type 2 diabetes (T2D), from which a pattern of depletion of butyrate producing taxa in T2D has emerged. Seventeen taxa encompass ~85% of the total butyrate producing potential in humans (mSystems 2017;2:e00130). The goal of MILES is to elucidate the effect of diet and gut microbiota on the components of insulin homeostasis (insulin sensitivity, secretion, clearance) whose dysfunction underlies T2D. MILES consists of 224 non-Hispanic Whites and 129 African Americans (mean age 59, 62% female), all of whom have completed an oral glucose tolerance test from which insulin homeostasis traits were calculated. Stool microbiome was assessed by whole metagenome shotgun sequencing (10 Gb depth), with taxonomic profiling using MetaPhlAn3. Spearman correlation was used to assess associations between the 17 dominant butyrate producing taxa (8 genera, 9 species) and insulin sensitivity, insulin secretion, disposition index (product of insulin sensitivity and insulin secretion), and insulin clearance. The Wilcoxon test was used to associate taxa with dysglycemia (prediabetes plus diabetes, 46% of cohort). Genera Coprococcus was associated with higher insulin sensitivity (ρ=0.16, P=0.003) and disposition index (ρ=0.14, P=0.009) and a lower rate of dysglycemia. Flavonifractor was associated with lower insulin sensitivity (ρ=-0.17, P=0.002) and a higher rate of dysglycemia. Eubacterium hallii was associated with insulin sensitivity (ρ=0.12, P=0.02). Analysis of 27 species from the 8 genera revealed additional associations with insulin sensitivity and disposition index, most of which displayed positive associations with these traits. These data suggest that improved insulin sensitivity and improved insulin secretion response to insulin sensitivity (i.e., disposition index) are key mechanisms whereby butyrate producing bacteria may exert metabolic protection against T2D. Disclosure: J. Cui: None. M. O. Goodarzi: None. T. Zhu: None. E. T. Jensen: None. O. L. Crago: None. G. Ramesh: None. K. M. Sandow: None. Y. Chen: None. J. I. Rotter: None. J. Petrosino: None. Funding: National Institutes of Health (R01DK109588) [ABSTRACT FROM AUTHOR]