Dietary fiber, gut microbiota, and host immunity: the immunomodulatory roles of short-chain fatty acids.

Short-chain fatty acids (SCFAs) are a class of key metabolites produced by the gut microbiota through the fermentation of indigestible components such as dietary fiber. They primarily include acetate, propionate, and butyrate. In recent years, a large body of research has revealed that SCFAs are not only an important energy source for colonic epithelial cells but also key signaling molecules linking the gut microbiota to the host immune system. SCFAs play a central role in immune regulation. This review summarizes the production and characteristics of SCFAs. It explores the multifaceted roles of SCFAs in regulating immune homeostasis and inflammatory responses. Through key mechanisms such as activation of G protein-coupled receptors (GPCRs), inhibition of histone deacetylases (HDACs), and metabolic reprogramming, SCFAs broadly regulate the differentiation, function, and inflammatory responses of immune cells, maintain intestinal barrier integrity, and induce an anti-inflammatory state. At the same time, the manuscript analyzes the molecular mechanisms by which SCFAs contribute to inflammatory bowel disease, metabolic disorders, tumor immunity, and neuro-immune diseases through multi-organ pathways such as the "gut-liver axis" and the "gut-brain axis". In addition, this article summarizes treatment strategies targeting SCFAs, including dietary interventions, probiotics, prebiotics, and fecal microbiota transplantation. It also discusses the current challenges in this field and outlines future directions, with the aim of providing new insights for the prevention and treatment of immune-related diseases.