The Role of Prebiotics on Nutrient Sensing and Metabolic Homeostasis in the Small Intestine
PublisherThe University of Arizona.
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AbstractMetabolic disorders like type 2 diabetes are a significant health and financial burden for many countries, particularly the United States, highlighting a need for successful treatment options. Therapeutic efforts to treat metabolic diseases are beginning to target the communities of bacteria residing in the gastrointestinal tract, coined the gut microbiota. The treatment of the gut microbiome with prebiotics like oligofructose (OFS) has demonstrated beneficial effects like reduced body weight, adiposity and even alleviating hallmark symptoms of T2D like insulin resistance. Previous OFS studies have observed an increase in secretion of gut peptides from enteroendocrine cells (EEC). Interestingly, it has been proposed that gut peptides can regulate glucose homeostasis, partly via a reduction of hepatic glucose production through a neuronal gut-brain-liver axis which is regulated by the small intestinal gut microbiota. In this study, we observe that altering the microbiome of high-fat (HF)-fed rodents via OFS treatment restores small intestinal nutrient-sensing mechanisms, which could lead to the improvements in glucose homeostasis. We observed that expression of nutrient sensor, CD36, in the jejunum of the small intestine was significantly decreased after high fat-feeding and restored with OFS treatment. Similarly, we observed an increase in GLP-1 release in the hepatic portal vein and increased c-FOS expression in the nucleus tractus solitarius (NTS) and area postrema (AP) of the hindbrain of prebiotic-treated HFD rats. Lastly, we observed an increase in c-FOS expression in the NTS and AP of the hindbrain of HFD-fed rats swapped with the microbiota of a prebiotic-treated HFD rat compared to the prebiotic-treated rat swapped with HFD-fed microbiota. Collectively, these results demonstrate the implications of HFD and the benefits of prebiotic treatment on the gut microbiota, small intestinal nutrient sensing, and metabolic homeostasis.