Short Chain Fatty Acids, pancreatic dysfunction and type 2 diabetes.

The microbiota living in gut influence the immune response, metabolism, mood and behavior. The diet plays a pivotal role in maintaining healthy gut microbiota composition and its fermentation leads to production of Short Chain Fatty Acids (SCFAs) mainly acetate, propionate and butyrate. During pancreatic dysfunction, insulin mediated suppression of glucagon is impaired leading to uncontrolled glucose production by liver and state of hyperglycemia. Insulin and glucagon balance is as important as insulin sensitivity which is reduced during Type 2 Diabetes (T2D). Glucagon like peptide-1 (GLP1) produced by Intestinal epithelial cells regulates insulin and glucagon secretion directly via GLP1 receptor on pancreatic cells or via nervous system. But half-life period of GLP1 is very short i.e. about 2 min, after which it is cleaved and inactivated. SCFAs are well documented to induce GLP1 but its direct effect on pancreatic dysfunction has not been reported. This review opens a new avenue to study the role of SCFAs as treatment to pancreatic dysfunction and T2D.

The Combinatorial Effect of Acetate and Propionate on High-Fat Diet Induced Diabetic Inflammation or Metaflammation and T Cell Polarization.

High-fat diet (HFD) alters the gut microbiota and its fermentation products mainly acetate, propionate, and butyrate. Butyrate is well studied as a regulator of host metabolism and inflammation while acetate and propionate still need to be studied. Therefore, we aim to decipher the role of acetate and propionate alone and in combination in HFD-induced diabetic mice. HFD was given to mice for 4 months followed by treatment of butyrate, acetate, and propionate as well as acetate + propionate in combination for 1 month. Diabetic outcome was confirmed by evaluating fasting glucose, lipid profile, oral glucose tolerance test, % HbA1c, fasting insulin, and glucagon. To check the immune response, spleen and mesenteric lymph node-specific T cell polarization and serum cytokine profile were studied. HFD-fed mice showed increased body weight and diabetic characteristics while treatment with acetate and propionate regulated their levels in a healthy manner similar to butyrate. In HFD-fed mice, Th1 and Th17 cells were increased while Treg cells were decreased along with increased pro-inflammatory cytokines and decreased IL-10 in serum. The T cell polarization and cytokine profile was reversed by the treatment of acetate and propionate alone and in combination. Acetate reduced the levels of IL-1ß and IL-6 and acetate + propionate reduced IL-6 more significantly than butyrate. Although, we did not find any synergistic effect in combination group, the results were better compared with acetate, propionate, and butyrate. In conclusion, acetate + propionate effectively reduced inflammation and improved insulin sensitivity in HFD-induced diabetic mice.