Abstract:

Sepsis， a systemic inflammatory disorder triggered by infection， is characterized by a complex pathophysiological mechanism that gives rise to high mortality rates and treatment bottlenecks. Short-Chain Fatty Acids （SCFAs）， as the core metabolites of the intestinal flora， exhibit potential in organ protection during sepsis via a multi-target regulatory mechanism. In the realm of immunomodulation， SCFAs achieve a balance between pro-inflammatory and anti-inflammatory responses by activating G protein-coupled receptors， inhibiting the activation of NLRP3 inflammasomes， and suppressing the cascade reaction of pro-inflammatory factors. At the metabolic regulation level， SCFAs optimize mitochondrial function， mitigate the hypercatabolic state associated with sepsis， and relieve organ energy failure. Furthermore， SCFAs exert an organ-protective effect in multiple ways. They enhance the integrity of the intestinal barrier， inhibit pathogen translocation， and impede the systemic spread of inflammation through the synergistic mechanisms of the intestinal-organ axis. Animal and preclinical studies have demonstrated that exogenous supplementation of SCFAs or dietary fiber intervention may interact with the intestinal flora， offering a novel strategy for sepsis treatment. In this review， we systematically summarize the multi-target regulatory network of SCFAs in sepsis and the research progress regarding their organ-protective effects in sepsis. Additionally， we propose therapeutic strategies targeting microbial metabolites， thereby providing a new perspective for overcoming the limitations of traditional anti-infection and immunomodulation.

Key words: sepsis, short-chain fatty acids, gut microbiota, intestine-organ axis