Gut microbiomes-host immune response and organ dysfunction across the gut-lung, gut-brain, and gut-liver axes

Microbial dysbiosis is associated with the onset and progression of disease and may influence host organ function through alterations in microbial metabolites, epithelial integrity, and immune signaling The gut communicates with distant organs through interconnected gut-lung, gut-brain, and gut-liver axes that contribute to physiological homeostasis. In the gut, short-chain fatty acid (SCFA)-producing microbes enhance mucin synthesis, epithelial barrier integrity, and immune regulation, while reduced intestinal pH may limit pathogen colonisation. In this review, we provide an integrated synthesis of evidence across the gut-lung, gut-brain, and gut-liver axes, focusing on how gut microbial dysbiosis and microbiota-derived metabolites influence host immune regulation and distant-organ function. Within the gut-brain axis, microbial metabolites, including SCFAs, can influence enteroendocrine signaling and vagal communication, thereby contributing to metabolic, emotional, and cognitive processes. Within the gut-liver axis, microbial alterations and metabolites are associated with hepatic metabolic dysfunction, inflammation, and lipid metabolic changes, with experimental evidence suggesting potential protective effects of Akkermansia muciniphila. By comparing the three gut-organ axes, this review identifies shared mechanisms involving SCFAs, microbial metabolites, epithelial barrier integrity, immune signaling, and neuroendocrine communication, while highlighting the current evidence gaps and priorities for future mechanistic and translational research.