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.

The gut has been a focus of chronic disease research. The gut microbiota produces metabolites that act as signaling molecules and substrates, closely influencing host health. Nondigestible oligosaccharides (NDOs), as a common dietary fiber, play an important role in regulating the structure and function of the gut microbiota. Their mechanism of action is mainly attributed to providing a carbon source as specific probiotics, producing related metabolites, and regulating the gut microbial community. However, due to the selective utilization of oligosaccharides, some factors, such as the type and structure of oligosaccharides, have different impacts on the composition of microbial populations and the production of metabolites in the colon ecosystem. This review systematically describes the key factors influencing the selective utilization of oligosaccharides by microorganisms and elaborates how oligosaccharides affect the host’s immune system, inflammation levels, and energy metabolism by regulating microbial diversity and metabolic function, which in turn affects the onset and progress of chronic diseases, especially diabetes, obesity, depression, intestinal inflammatory diseases, and constipation. In this review, we re-examine the interaction mechanisms between the gut microbiota and its associated metabolites and diseases, and we explore new strategies for promoting human health and combating chronic diseases through dietary interventions.

The gut has been a focus of chronic disease research. The gut microbiota produces metabolites that act as signaling molecules and substrates, closely influencing host health. Indigestible oli-gosaccharides (NDOs), as a common dietary fiber, play an important role in regulating the structure and function of gut microbiota. Their mechanism of action is mainly attributed to their carbon source as specific probiotics, producing related metabolites, and regulating the gut mi-crobial community. However, due to the selective utilization of oligosaccharides, some factors such as the types and structures of oligosaccharides have different impacts on the composition of microbial populations and the production of metabolites in the colon ecosystem. This review systematically describes the key factors influencing the selective utilization of oligosaccharides in microorganisms and elaborates how oligosaccharides affect the host's immune system, inflam-mation levels and energy metabolism by regulating microbial diversity and metabolic function, which in turn will affect the onset and progress of chronic diseases, especially diabetes, obesity, depression and intestinal inflammatory diseases, constipation. In this review, we re-examine the interaction mechanisms between gut microbiota and its associated metabolites and diseases, and explore new strategies for promoting human health and combating chronic diseases through di-etary interventions.