Novel insights into immune mechanisms in acute lung injury: Focusing on gut microbiota and its metabolites.

Acute lung injury (ALI) is a critical clinical syndrome of the respiratory system, for with a lack of effective preventive/therapeutic strategies. Advances in gutlung axis research have elucidated how the gut drives lung diseases, opening new avenues for acute lung injury intervention. This review synthesizes evidence positioning the gut-lung axis as a dynamic immunomodulatory network to ALI pathogenesis. We propose a three-pronged mechanistic framework for gut-originated ALI: (1) dysbiosis of the gut microbiota and its metabolites, (2) disruption of the intestinal barrier, and (3) pulmonary microbiota dysbiosis coupled with mesenteric lymph-mediated pulmonary inflammation. This framework delineates how gut dysbiosis orchestrates a cascade of events-from metabolite-driven immune dysregulation to barrier breach-induced pulmonary microbial disruption and mesenteric lymph-mediated inflammation-culminating in the progression of acute lung injury. Finally, we discuss approaches to restore gut microbiota homeostasis, the challenges inherent in this strategy, and the imperative of bridging fundamental discoveries with clinical translation challenges.