229-OR: The Gut Microbiome in Adults with Prediabetes and Effect of Dietary Glycemic Index

Abstract

Compositional and functional differences in gut bacteria exist between adults with normal glucose tolerance, IGT and type 2 diabetes and can change with dietary factors. We compared the gut microbiome between adults with impaired fasting glucose (IFG), impaired glucose tolerance (IGT) and IFG+IGT and evaluated the impact of dietary glycemic index (GI) on the gut microbiome. The study enrolled 53 adults (mean±SEM: age 53.0±1.4 y, BMI 32.5±0.9 kg/m2) with IFG (n=20), IGT (n=10) or both IFG+IGT (n=23). Stool samples were collected in RNAlater after 2 weeks on a control, moderate GI diet (GI 55-58) and again after a 4 week dietary intervention of a low GI (GI<35, n=18) or high GI diet (GI>70, n=18 on placebo and n=17 on the antioxidant N-acetyl-cysteine 1200 mg po BID). Diets had the same macronutrient composition (55%carbohydrate/30% fat/15% protein) but more fiber in the LGI (65.1±2.2 g/d) vs. HGI diet (25.8±0.8 g/d). The stool microbiome was analyzed using 16S rRNA gene sequencing (V1-V3). Results: α diversity was significantly higher in IGT vs. IFG+IGT (7.2±0.08 vs. 7.0±0.06, p<0.05). Linear regression analysis adjusted for age, sex, BMI, race and sequencing plate showed 3 genera differed across groups on the control diet: Fusicatenibacter (p=0.01) and Lachnospiraceae UCG-008 (p=0.02) were lower in IGT vs. IFG+IGT; Oxalobacter was reduced in IFG (p=0.04) and enriched in IGT (p=0.004) vs. IFG+IGT. After 4 weeks on LGI or HGI diets α diversity did not differ and NAC had no effect on the microbiome. Adjusted regression analysis showed only the genus Anaerostipes differed, being higher in the LGI group (p<0.0001). Conclusions: Differences in microbiota were observed between IGT and IFG+IGT. These associations may contribute to poorer metabolic function in IFG+IGT, but would need further testing to determine cause and effect. The LGI diet was associated with higher Anaerostipes, a butyrate producing bacteria with beneficial anti-inflammatory effects. This may be related to the higher fiber content of the LGI diet. Disclosure K. Utzschneider: Other Relationship; Self; Medtronic. M.L. Neuhouser: None. K.M. Newton: None. K. Breymeyer: None. M.A. Hullar: None. Funding National Institutes of Health (R01DK092568, P30DK017047, UL1TR002319, P30CA015704, KL2TR002317, TL1TR002318)