Prebiotic Dietary Fiber Consumption Improves Glucose Tolerance and Modulates Gastrointestinal Microbiota Composition in Overweight/Obese Adults with Impaired Fasting Glucose

Background Soluble fermentable fibers, like inulin and fructo‐oligosaccharides (FOS), have been designated as prebiotics. In humans, inulin and FOS are selectively fermented by endogenous bacteria in the lower gastrointestinal (GI) tract resulting in an increase in the relative amounts of purported beneficial bacteria (e.g., bifidobacteria, lactobacilli). Additionally, prebiotics have been shown to modulate specific host metabolic parameters, although results have been mixed. Objective This single‐arm exploratory study investigated whether daily supplementation of FOS‐enriched inulin selectively modulates GI microbial structure, while exerting beneficial effects on glycemic control in overweight/obese adults with impaired fasting glucose (IFG). Methods Study subjects included 8 adult males of non‐Hispanic white (n=4), black/African American (n=3), or Asian/Pacific Islander (n=1) race/ethnicity, with mean ± SEM age of 44.1 ± 2.9 y, BMI of 30.2 ± 1.2 kg/m2, body fat % (via dual energy x‐ray absorptiometry) of 33.4 ± 1.4%, and fasting glucose concentration of 109.3 ± 2.7 mg/dL at screening. All subjects consumed 8 g/day of a commercially available FOS‐enriched inulin over a 3‐week period. Subjects provided two fecal samples, fasting blood samples for analysis of lipoprotein lipids and a targeted metabolite profile, 3‐day diet records, and a 3‐day bowel habits diary prior to and at the end of the 3‐week test period. Additionally, all participants provided blood samples for measurement of circulating insulin and glucose in response to a standard oral glucose tolerance test (OGTT; 75 g glucose) at baseline and end of study. Alterations in microbial community structure of stool samples were assessed using Illumina MiSeq sequencing of the 16s rRNA V4‐V5 region. Results On average, there were no statistically significant changes from baseline in fasting glucose, insulin, lipoprotein lipids, or indicators of glucose tolerance associated with the OGTT for the entire group. However, the calculated insulin sensitivity (Matsuda composite index; MISI) determined from the OGTT (MISI Δbaseline = 1.87 ± 0.95) of 4 subjects suggested improvements in glucose tolerance indicated by reductions in the area under the curve (AUC 0–120 min ) for glucose (−2430 mg*min/dL) and insulin (−3111 μIU*min/mL) after the 3‐week intervention. Conversely, the remaining 4 subjects experienced either no change in, or a worsening of, MISI over the 3‐week period (−3.05 ± 2.09) with corresponding increases in the AUC 0–120 min for glucose (2348 mg*min/dL) and insulin (5471 μIU*min/mL). Therefore, 16s rRNA sequencing analyses were performed to determine whether OGTT “responders” and “nonresponders” displayed differences in microbial community structure. While no changes were found in membership based on alpha diversity metrics, Principal Coordinate Analysis (PCoA) of abundance‐weighted beta‐diversity showed that microbial communities significantly differed between responders and nonresponders (p = 0.003). After supplementation, responders displayed increased abundance of the phyla Bacteroidetes and Actinobacteria and decreased abundance of Firmicutes and Proteobacteria compared to baseline, whereas no apparent differences were found in nonresponders. Conclusion These data suggest that prebiotic dietary fiber consumption may mediate improvements in glucose tolerance in overweight/obese adults with IFG, with associated shifts in gut microbiota composition. Support or Funding Information This study was funded by Biofortis Clinical Research and NIH grants T32DK007074, P30DK42086, DK097268.