Abstract
Butyrate is a key short-chain fatty acid (SCFA) essential for maintaining colon health, immune homeostasis, and metabolic balance. Its synthesis primarily depends on the fermentation of dietary substrates by the gut microbiota. In a healthy state, carbohydrate fermentation sustains the stability of the gut microbiota; however, in chronic diseases, the diversity of the microbiota decreases, and the metabolic pathway shifts from carbohydrate fermentation to protein fermentation, thereby inhibiting butyrate production. Polysaccharides and proteins play key roles in regulating butyrate synthesis. As fermentable carbon sources, polysaccharides promote the proliferation of probiotics, lower colonic pH, and inhibit anaerobic fermentation of proteins. However, excessive protein fermentation produces branched-chain fatty acid (BCFA), ammonia, phenols, and other metabolites that inhibit butyrate production. The structural characteristics of polysaccharides and the digestibility of proteins can determine the substrate selection of gut microbiota. This review systematically elucidates the biosynthetic pathways of butyrate in the gut and the host metabolic signaling pathways in which it participates, focusing on the interactions between dietary proteins and polysaccharides and their key regulatory mechanisms affecting butyrate production by the gut microbiota.