The roles and applications of short-chain fatty acids derived from microbial fermentation of dietary fibers in human cancer

Abstract

Dietary fibers (DFs) and their metabolites attract significant attention in research on health and disease, attributing to their effects on regulating metabolism, proliferation, inflammation, and immunity. When fermented by gut microbiota, DFs mainly produce short-chain fatty acids (SCFAs), such as acetic acid, propionic acid, and butyric acid. As the essential nutrients for intestinal epithelial cells, SCFAs maintain intestinal homeostasis and play essential roles in a wide range of biological functions. SCFAs have been found to inhibit histone deacetylase, activate G protein-coupled receptors, and modulate the immune response, which impacts cancer and anti-cancer treatment. Notably, while extensive studies have illuminated the roles of SCFAs in colorectal cancer development, progression, and treatment outcomes, limited evidence is available for other types of cancers. This restricts our understanding of the complex mechanisms and clinical applications of SCFAs in tumors outside the intestinal tract. In this study, we provide a comprehensive summary of the latest evidence on the roles and mechanisms of SCFAs, with a focus on butyric acid and propionic acid, derived from microbial fermentation of DFs in cancer. Additionally, we recapitulate the clinical applications of SCFAs in cancer treatments and offer our perspectives on the challenges, limitations, and prospects of utilizing SCFAs in cancer research and therapy.

Unraveling the gut microbiome’s contribution to pancreatic ductal adenocarcinoma: mechanistic insights and therapeutic perspectives

“…SCFAs exert anticancer effects by inhibiting cell growth and migration, suppressing histone deacetylase activity, and inducing apoptosis. These actions contribute to the prevention and treatment of gastrointestinal and lung cancers ( 114 ). The regulation of gut microbiota has a direct or indirect impact on SCFA concentration, offering potential strategies for cancer treatment.…”

Unveiling the Gut Microbiome: How Junk Food Impacts the Gut

“…Healthy eaters have a rich diversity of beneficial bacteria, such as bifidobacteria and lactobacilli, which are essential for digestion, production of SCFA, and gut wall reinforcement [ 49 ]. Junk food, on the other hand, encourages the expansion of harmful microorganisms like Firmicutes, linked to inflammation and obesity.…”