Short-chain fatty acid metabolism in acute lung injury and intervention strategies from traditional Chinese medicine

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are severe conditions associated with high mortality rates and limited treatment options. Short-chain fatty acids (SCFAs) serve as central immunomodulatory metabolites mediate the crosstalk between the gut and lung. Traditional Chinese medicine (TCM), with its holistic approach, shows promise in restoring gut-lung balance and alleviating respiratory inflammation by modulating gut microbiota and SCFA metabolism.

To elucidate the protective role and mechanism of SCFAs in ALI and ARDS via the gut-lung axis. Meanwhile, to evaluate the therapeutic potential of TCM in treating ALI by modulating the gut microbiota and enhancing SCFA production.

A comprehensive literature search was conducted across PubMed, Ovid-Embase, Web of Science, and CNKI databases (2010-2025). Keywords included "short-chain fatty acid", "gut microbes", "acute lung injury", "traditional Chinese medicine", and related terms. The search focused on preclinical and mechanistic studies investigating SCFA signaling, gut microbiota remodeling, and the therapeutic effects of herbal compounds or their active constituents in ALI/ARDS models.

This review identified acetate, propionate, and butyrate as key mediators that protect against ALI through distinct mechanisms, including anti-oxidation, anti-inflammation, immunomodulation, apoptosis reduction, airway tight-junction protection, and regulation of intestinal homeostasis. In addition, 9 bioactive components, 5 single-herb extracts, and 4 Chinese herb formulations were found to ameliorate ALI by enriching SCFA-producing bacteria, such as Akkermansia, Lactobacillus, and Lachnospiraceae, thereby elevating systemic and local levels of acetate, propionate, and butyrate.

SCFAs represent critical molecular mediators of the gut-lung axis, and their modulation by natural products offers a promising microbiota-centered strategy for ALI treatment. This microbiota-centered strategy holds great promise for ALI precision medicine.