Short-chain fatty acids and the gut–lung axis: implications for pulmonary inflammation

The gut-lung axis between the gastrointestinal tract and the respiratory system has emerged as an influencing factor of pulmonary immune system inflammation and homeostasis. Short-chain fatty acids (SCFAs)--most notably acetate, propionate, and butyrate––are essential compounds to this system, acting as messengers during cell trafficking. These SCFAs are microbial metabolites derived from the fermentation of dietary fibers in the gut. There is strong evidence that SCFAs migrate through the bloodstream and mitigate pulmonary inflammation across several diseases, including acute lung injury (ALI). There are two main mechanisms through which SCFAs impact pulmonary inflammation. First, signaling via G-protein-coupled receptors to suppress pro-inflammatory cytokines. Second is a form of epigenetic regulation in which histone deacetylases (HDACs) are inhibited, which participates in the reprogramming of regulatory T (Treg) cells and the alteration of alveolar macrophages toward the resolution-phase. SCFA-based interventions have high therapeutic potential for humans through high-fiber diets and postbiotic administration of inactivated organisms and their metabolites, which may aid in pulmonary inflammation.  Novelty of the Study: This review analyzes the differential roles of SCFAs in regulating pulmonary inflammation through GCPR signaling and epigenetic mechanisms. It explores how personalized fiber-focused diet plans as well as postbiotic therapies, tracked by active biomarkers, may help treat acute and chronic lung conditions.