Butyrate-producing bacteria and insulin homeostasis: The Microbiome and Insulin Longitudinal Evaluation Study (MILES)

Authors: CUI, JINRUI - Cedars-Sinai Medical Center; RAMESH, GAUTAM - University Of California, San Diego; WU, MARTIN - University Of Virginia; JENSEN, ELIZABETH - Wake Forest School Of Medicine; CRAGO, OSA - Wake Forest School Of Medicine; BERTONI, ALAIN - Wake Forest School Of Medicine; GAO, CHUNXU - Baylor College Of Medicine; HOFFMAN, KRISTI - Baylor College Of Medicine; SHERIDAN, PATRICIA - Metabolon, Inc; WONG, KARI - Metabolon, Inc; WOOD, ALEXIS - Children'S Nutrition Research Center (CNRC); CHEN, YII - Harbor-Ucla Medical Center; ROTTER, JEROME - Harbor-Ucla Medical Center; PETROSINO, JOSEPH - Baylor College Of Medicine; RICH, STEPHEN - University Of Virginia; GOODARZI, MARK - Cedars-Sinai Medical Center

Submitted to: Diabetes
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 8/2/2022
Publication Date: 8/12/2022
Citation: Cui, J., Ramesh, G., Wu, M., Jensen, E.T., Crago, O., Bertoni, A.G., Gao, C., Hoffman, K.L., Sheridan, P.A., Wong, K.E., Wood, A.C., Chen, Y.D., Rotter, J.I., Petrosino, J.F., Rich, S.S., Goodarzi, M.O. 2022. Butyrate-producing bacteria and insulin homeostasis: The Microbiome and Insulin Longitudinal Evaluation Study (MILES). Diabetes. https://doi.org/10.2337/db22-0168.
DOI: https://doi.org/10.2337/db22-0168

Interpretive Summary: The bacteria in our gut, known as our 'gut microbiome', play a critical role in digesting the food we eat. Because type 2 diabetes (T2D) arises when people have too much sugar in their blood after eating carbohydrates, scientists think that the types of bacteria in each person's gut can influence their risk of developing T2D. The problem is that we don't know which bacteria increase the risk of T2D developing, and which decrease the risk. Researchers in Houston studied the gut bacteria of older US adults, and identified almost 20 types of bacteria that work together to improve how well the body reduces sugar in the blood after a sugary meal. This may eventually help us identify pathways underlying T2D, and give clues into treatment options to reduce either the onset of T2D or its effects on health once a diagnosis has been made.

Technical 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 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 (Beta=0.14, P=0.002) and disposition index (Beta=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 (Beta=-0.13, P=0.004) and disposition index (Beta=-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.