Short-Chain Fatty Acids: A Key Modulator of Sepsis-Associated Acute Respiratory Distress Syndrome

Sepsis-associated acute respiratory distress syndrome (ARDS) is a common clinical fatal complication, and intestinal flora imbalance has been proved to be a key link in the mechanism of morbidity. Intestinal dysbacteriosis directly contributes to lung injury through mechanisms such as microbial translocation, systemic inflammation, and immune dysregulation, and depletion of short-chain fatty acids (SCFAs) as key protective metabolites is an important driver of ARDS progression. SCFAs, mainly including acetate, propionate and butyrate, exert anti-inflammatory, immunomodulatory and barrier protective effects by inhibiting histone deacetylase (HDACs) and activating G protein-coupled receptors (GPCRs). However, SCFAs also exhibit concentration, type, and inflammation stage-dependent bidirectional regulatory properties. Clearly defining this bidirectional regulation is a critical factor for precision dosing and personalized therapies in a clinical setting. This article systematically reviews the causal mechanism of ARDS caused by intestinal flora imbalance, the bidirectional regulation of SCFAs, and the intervention strategies based on intestinal flora, providing new ideas for the precise treatment of sepsis-associated ARDS.