Gut microbiota-derived short-chain fatty acids (SCFAs): immunomodulatory effects and therapeutic potential in infections

SUMMARY The human gut microbiotas constitute a complex microecosystem essential for host homeostasis. Among its metabolites, short-chain fatty acids (SCFAs) act as key signaling molecules linking microbial activity to host immunity and barrier function. Based on existing literature, we conducted a comprehensive analysis of the interaction between SCFAs and 11 key gut pathogens. These pathogens include bacteria (i.e., Staphylococcus aureus , Clostridioides difficile, Salmonella spp. , Campylobacter jejuni, Klebsiella pneumoniae, Vibrio cholerae ), fungi (i.e., Candida albicans ), and viruses (i.e., SARS-CoV-2, influenza virus, respiratory syncytial virus, rotavirus). In terms of antibacterial effects, SCFAs exhibit antibacterial activity against most gut microorganisms, but they support the colonization of a few species (i.e., Campylobacter jejuni ). Given the complex interactions between SCFAs and the gut microbiota, as well as their regulatory roles in infection, further investigation of the microbiota-SCFA axis is essential for developing effective strategies to prevent and treat infectious diseases. This review systematically summarizes the mechanism and clinical evidence of SCFAs in microbial infections to provide novel ideas for infectious disease management.