Formation of short chain fatty acids by the gut microbiota and their impact on human metabolism

Abstract

The formation of SCFA is the result of a complex interplay between diet and the gut microbiota within the gut lumen environment. The discovery of receptors, across a range of cell and tissue types for which short chain fatty acids SCFA appear to be the natural ligands, has led to increased interest in SCFA as signaling molecules between the gut microbiota and the host. SCFA represent the major carbon flux from the diet through the gut microbiota to the host and evidence is emerging for a regulatory role of SCFA in local, intermediary and peripheral metabolism. However, a lack of well-designed and controlled human studies has hampered our understanding of the significance of SCFA in human metabolic health. This review aims to pull together recent findings on the role of SCFA in human metabolism to highlight the multi-faceted role of SCFA on different metabolic systems.

Keywords: glucose homeostasis; gut microbiota; host metabolic health; inflammation; short chain fatty acids.

Figure 1.

The gut lumen is the major site of production but the concentration gradient falls from the lumen to the periphery with selective uptake of butyrate at the epithelium, propionate at the liver and acetate in the periphery. The significance for host physiology of this biological gradient is poorly understood.

Figure 2.

SCFA along with other metabolites entering the hepatic portal system are rapidly transported to the liver. The role of molecular signaling on different liver cell types is poorly characterized. SCFA can act on resident macrophages and hepatocytes although there may be functional selectivity for each SCFA. Incretion hormones may also act on hepatocytes and peripheral tissues. The overall impact of this dual signaling system appears to be maintenance of a healthy liver through regulation of hepatic metabolism and inflammation and control of adipose derived FFA flux. The peripheral effects of SCFA appear tissue specific. SCFA can regulate insulin in the pancreas, FFA flux from adipocytes, appetite centers in the brain and provide a fuel for the muscle. This multi-faceted role however, requires further investigation with well-designed and controlled studies in humans.