Emerging role of nutritional short-chain fatty acids (SCFAs) against cancer via modulation of hematopoiesis

The understanding of gut microbiota has emerged as a significant frontier in development of strategies to maintain normal human body's homeostasis and preventing the disease development over the last decade. The composition of the gut microbiota influences the clinical benefit of immune checkpoints in patients with advanced cancer, but the mechanisms underlying this relationship are unclear. Cancer is among the leading causes of mortality worldwide. So far, there is no universal treatment for cancer and despite significant advances, a lot of improvement on cancer therapy is required. Owing to its role in preserving the host's health and maintaining cellular integrity, the human gut microbiome has recently drawn a lot of interest as a target for cancer treatment. Dietary fiber is fermented by the gut microbiota to generate short-chain fatty acids (SCFAs), such as acetate, butyrate, and propionate, which are physiologically active metabolites. SCFAs can modulate the pathophysiology of the tumor environment through various critical signaling pathways. In addition, SCFAs can bind to carcinogens and other toxic chemicals, thus facilitating their biotransformation and elimination through different excretory mechanisms. This review discusses the mechanisms of action of short-chain fatty acids in modulating hematopoiesis of various immune system cells and the resultant beneficial anti-cancer effects. It also provides future perspectives on cancer therapy.