The Gut Microbiota and Short-Chain Fatty Acids in Association With Glycemia and Adiposity in Young Adults With Type 1 Diabetes: The ACT1ON Ancillary Gut Microbiome Pilot Study

Abstract

ObjectivesCo-managing glycemia and adiposity is the cornerstone of cardiometabolic risk reduction among people with type 1 diabetes (T1D) but targets are often not met. The gut microbiota and microbiota-derived short-chain fatty acids (SFCA) influence glycemia and adiposity but have not been sufficiently investigated in longstanding T1D. We hypothesized that an increased abundance of SCFA-producing gut microbes, fecal SCFA, and gut microbial diversity were associated with improved glycemia but increased adiposity among young adults with longstanding T1D.MethodsParticipants provided stool samples at up to four time points. 16S rRNA gene sequencing determined the abundance of SCFA-producing gut microbes. Gas-chromatography mass-spectrometry determined total and specific SCFA (acetate, butyrate, and propionate). Dual-energy x-ray absorptiometry (% body fat or lean mass) and anthropometrics (body mass index [BMI]) measured adiposity. Continuous glucose monitoring (time in range [70–180 mg/dl], above range [>180 mg/dl], and below range [54–69 mg/dl]) and hemoglobin A1c assessed glycemia. Adjusted and Bonferroni-corrected generalized estimating equations modeled the associations of SCFA-producing gut microbes, fecal SCFA, and gut microbial diversity with glycemia and adiposity. COVID-19 interrupted data collection, so models were repeated with restriction to pre-COVID visits.ResultsData were available for up to 45 participants at 101 visits, including 40 participants at 54 visits pre-COVID. The abundance of Eubacterium hallii was associated inversely with BMI (all data). Pre-COVID, increased fecal propionate was associated with increased time above range and reduced time in target and below range; and the increased abundance of four SCFA-producing intestinal microbes (Ruminococcus gnavus, Ruminococcus 2, Eubacterium ventriosum, and Lachnospira) was associated with reduced adiposity (% body fat or BMI), of which two microbes were also associated with increased % lean mass.ConclusionsUnexpectedly, fecal propionate was associated with detriment to glycemia, while several SCFA-producing gut microbes were associated with benefit to adiposity. Future mechanistic studies may determine whether these associations have causal linkages in T1D.Funding SourcesNational Institute of Diabetes and Digestive and Kidney Diseases.