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

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 (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.

High-Resolution Taxonomic Characterization Reveals Novel Human Microbial Strains with Potential as Risk Factors and Probiotics for Prediabetes and Type 2 Diabetes

“…Another genus and species that increased in abundance and could be involved in the development of type 2 diabetes were Flavonifractor plautii and an unclassified Flavonifractor species, which were more abundant in type 2 diabetes participants than prediabetes/healthy participants. This pattern supports previous findings showing that the genus Flavonifractor decreased in prediabetes and increased in type 2 diabetes [ 41 ], and was associated with a lower insulin sensitivity and higher prevalence of dysglycemia [ 42 ]. F. plautii , specifically, was lower in patients with prediabetes and higher in patients with diabetes [ 41 , 43 ].…”

A network perspective on the ecology of gut microbiota and progression of type 2 diabetes: Linkages to keystone taxa in a Mexican cohort

“…In accordance with the LEfSe analysis, all identified bacteria belong to genera with previous reports linked to the progression of insulin resistance in T2D ( Figure 6 ). However, Coprococcus_1 , found in the T2D treated group, was already characterized by a high insulin sensitivity (β = 0.14; P = 0.002) and disposition index (β = 0.12; P = 0.012); for this reason, we hypothesized that its effect was mostly related to the changes in the constant metformin consumption in T2D patients ( 89 ). Furthermore, this is the first association of Fournierella with T2D patients and metformin treatment.…”

Alterations in gut microbiota and bile acids by proton‐pump inhibitor use and possible mediating effects on elevated glucose levels and insulin resistance

“…The noted mediation effect provided supporting evidence that oral bacteria may play critical roles in PPI‐induced side effects, such as diabetes. As a potentially pro‐inflammatory species, Fusobacterium could induce low‐grade systemic inflammation, 36,37 thereby causing hepatic and peripheral insulin resistance, and glucose metabolism disorders 21,38 . Therefore, interventions such as mouthwash and probiotic supplements might be a solution to reduce microbiome‐related side effects of PPIs, such as diabetes, but the potential effects warrant further study 39,40 …”