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

Authors

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

Publication Date

11-1-2022

Journal

Diabetes

DOI

10.2337/db22-0168

PMID

35972231

PMCID

PMC9630078

PubMedCentral® Posted Date

8-12-2022

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes

Keywords

Humans, Insulin, Insulin Resistance, Diabetes Mellitus, Type 2, Blood Glucose, Insulin, Regular, Human, Homeostasis, Microbiota, Butyrates

Abstract

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 among 36 butyrate-producing taxa (n = 7 genera and 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, BMI, and race. The 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 [OR] 0.91; 95% 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. Although 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.