Short-Chain Fatty-Acid-Producing Micro-Organisms Regulate the Pancreatic FFA2-Akt/PI3K Signaling Pathway in a Diabetic Rat Model Affected by Pumpkin Oligosaccharides

Herein, we applied the Illumina MiSeq pyrosequencing platform to amplify the V3–V4 hypervariable regions of the 16 S rRNA gene of the gut microbiota (GM) and a gas chromatograph–mass spectrometer to detect the metabolites after supplementation with pumpkin oligosaccharides (POSs) to determine the metabolic markers and mechanisms in rats with type 2 diabetes (T2D). The POSs alleviated glucolipid metabolism by decreasing the serum low-density lipoprotein (LDL), total cholesterol (TC), and glucose levels. These responses were supported by a shift in the gut microbiota, especially in the butyric-acid-producing communities. Meanwhile, elevated total short-chain fatty acid (SCFA), isovaleric acid, and butyric acid levels were observed after supplementation with POSs. Additionally, this work demonstrated that supplementation with POSs could reduce TNF-α and IL-6 secretion via the FFA2-Akt/PI3K pathway in the pancreas. These results suggested that POSs alleviated T2D by changing the SCFA-producing gut microbiota and SCFA receptor pathways.