Evidence for the gut microbiota short-chain fatty acids as key pathophysiological molecules improving diabetes

Abstract

In type 2 diabetes, hyperglycemia, insulin resistance, increased inflammation, and oxidative stress were shown to be associated with the progressive deterioration of beta-cell function and mass. Short-chain fatty acids (SCFAs) are organic fatty acids produced in the distal gut by bacterial fermentation of macrofibrous material that might improve type 2 diabetes features. Their main beneficial activities were identified in the decrease of serum levels of glucose, insulin resistance as well as inflammation, and increase in protective Glucagon-like peptide-1 (GLP-1) secretion. In this review, we updated evidence on the effects of SCFAs potentially improving metabolic control in type 2 diabetes.

Figure 1

SCFAs improve metabolic functions in T2D. SCFAs were shown to affect pancreatic beta-cell function by directly acting as HDAC inhibitors (promoting β-cell development, proliferation, and differentiation) or by indirectly increasing GLP-1 secretion from enteroendocrine L-cells (leading to insulin release). Furthermore, SCFAs reduce the release of proinflammatory cytokines by adipose tissue and weaken leukocyte activation. These anti-inflammatory effects improve insulin resistance, tissue glucose uptake, and blood glucose levels.