The protective role of short-chain fatty acids acting as signal molecules in chemotherapy- or radiation-induced intestinal inflammation.

Abstract

A compelling set of links between chemotherapy- or radiation-induced intestinal inflammation and microbial dysbiosis has emerged. It is the proportional imbalance between pathogenic and beneficial bacteria that aggravates intestinal mucositis. Bacteria that ferment fibers and produce short-chain fatty acids (SCFAs), (such as acetate, propionate, and butyrate) are typically reduced in the mucosa and feces of patients undergoing cancer therapy. In contrast, increasing lipopolysaccharide-producing bacteria result in proinflammatory events by interacting with Toll-like receptors. A collective acceptance is that bacterial metabolites are critical in recovering intestinal homeostasis. We herein review evidence supporting the positive roles carried out by SCFAs. SCFAs, acting as signaling molecules, directly activate G-coupled-receptors and inhibit histone deacetylases. Thus, SCFAs are able to strengthen the gut barrier and regulate immunomodulatory functions. Furthermore, it is possible to reverse intestinal microbial dysbiosis and subsequently suppress the secretion of proinflammatory cytokines by directly applying SCFA-producing bacteria. In addition, anticancer effects of SCFAs have proved in the colorectal cancer. In this review, we discuss microbial dysbiosis and its impact on chemotherapy- or radiation-induced intestinal mucositis. Moreover, we summarize the mechanisms of SCFA production and its effects on intestinal mucositis. This review suggests the therapeutic potential of SCFAs for the management of chemotherapy- or radiation-induced intestinal inflammation.