The Role of Oligofructose in Altering Small Intestinal Nutrient Sensing via the Gut Microbiota

Abstract

Impairments in glucose homeostasis and insulin sensitivity in type II diabetic patients can be improved via manipulations to the gut microbiota. As such, therapies that alter the gut microbiota could serve as alternative treatments for diabetes and metabolic disorders. Treatment with the prebiotic oligofructose (OFS), a non-digestible carbohydrate known to beneficially alter the distal gut microbiota, decreases glucose production potentially via a gut-brain signal, although the exact mechanism remains unknown. As no studies have examined the effect of OFS on the small intestinal microbiota and given the recent evidence that the small intestinal microbiota can impact small intestinal nutrient sensing to regulate hepatic glucose production, we tested the hypothesis that OFS can restore the gut-brain-liver axis to decrease glucose production in response to a small intestinal nutrient infusion, which is abolished with high fat (HF)- feeding. We found that three-days of high fat feeding abolished the ability of small intestinal nutrients to decrease glucose production during euglycemic (basal insulin) pancreatic clamps. Both small intestinal carbohydrate and lipid nutrient sensing to decrease glucose production were restored in HF-fed rodents following two-day OFS supplementation. Microbiota swaps from HF+OFS treated donor rats into HF-fed recipient rats replicated the decrease in glucose production in response to carbohydrate or lipid small intestinal infusions. Lastly, we are the first to show that OFS treatment alters the small intestinal microbiota and that these shifts can impact small intestinal nutrient sensing to regulate glucose production.