Staphylococcus aureus (S. aureus) is a common pathogen that can cause many human diseases, such as skin infection, food poisoning, endocarditis, and sepsis. These diseases can be minor infections or life-threatening, requiring complex medical management resulting in substantial healthcare costs. Meanwhile, as the critically ignored “organ,” the intestinal microbiome greatly impacts physiological health, not only in gastrointestinal diseases but also in disorders beyond the gut. However, the correlation between S. aureus infection and intestinal microbial homeostasis is largely unknown. Here, we summarized the recent progress in understanding S. aureus infections and their interactions with the microbiome in the intestine. These summarizations will help us understand the mechanisms behind these infections and crosstalk and the challenges we are facing now, which could contribute to preventing S. aureus infections, effective treatment investigation, and vaccine development.

The mammalian respiratory system stands as a frontline barrier, constantly exposed to environmental insults, balancing defensive immunity with gas exchange. Historically considered sterile, the lung harbors a dynamic, low-biomass microbiome that evolves con-tinuously in response to pulmonary pathologies. Accumulating evidence underscores that respiratory health and structural recovery are not autonomous but are critically integrated with distal microbial systems, especially the intestinal tract, through the gut-lung axis (GLA). This review characterizes the GLA as a bidirectional communication highway fueled by immune pathways, microbial metabolites, and direct microbial translocations. During acute or chronic injuries, such as COVID-19, COPD, asthma, and idiopathic pul-monary fibrosis (IPF), the gut microbiota serves as a remote metabolic "rheostat". It delivers pivotal signaling molecules, such as short-chain fatty acids (SCFAs) and tryptophan me-tabolites (indoles), to determine whether the respiratory epithelium undergoes functional repair or maladaptive, fibrotic remodeling. Mechanistically, gut-derived butyrate enhances mitochondrial oxidative phosphorylation to supply the metabolic yield required for resi-dent progenitors, such as Alveolar Type 2 (AT2) cells, to transition from quiescence to pro-liferation. Conversely, critical lung illness disrupts this homeostasis via a "pathological circuit," where severe pulmonary inflammation drives gut permeability, fecal dysbiosis, and the subsequent translocation of pathogen-associated molecular patterns (PAMPs, such as LPS) or gut-associated bacteria back into the pulmonary circulation. This review highlights the systemic nature of lung regeneration, which depends heavily on intestinal health through the gut-lung axis. Ultimately, leveraging these remote microbial networks through precision postbiotics, dietary priming, or microbiota transplantation represents a crucial frontier in precision medicine to promote definitive alveolar repair.

The mammalian respiratory system stands as a frontline barrier, constantly exposed to environmental insults, balancing defensive immunity with gas exchange. Historically considered sterile, the lung harbors a dynamic, low-biomass microbiome that evolves continuously in response to pulmonary pathologies. Accumulating evidence underscores that respiratory health and structural recovery are not autonomous but are critically integrated with distal microbial systems, especially the intestinal tract, through the gut–lung axis (GLA). This review characterizes the GLA as a bidirectional communication highway fueled by immune pathways, microbial metabolites, and direct microbial translocations. During acute or chronic injuries, such as COVID-19, COPD, asthma, idiopathic pulmonary fibrosis (IPF) and lung cancer, the gut microbiota serves as a remote metabolic “rheostat”. It delivers pivotal signaling molecules, such as short-chain fatty acids (SCFAs) and tryptophan metabolites (indoles), that could shape the local microenvironment in which the respiratory epithelium undergoes functional repair or maladaptive, fibrotic remodeling. Mechanistically, gut-derived butyrate enhances mitochondrial activity in alveolar epithelial cells, while resident progenitors, such as Alveolar Type 2 (AT2) cells, depend on intact mitochondrial fatty acid oxidation for proper regenerative differentiation. Conversely, critical lung illness disrupts this homeostasis via a “pathological circuit,” where severe pulmonary inflammation drives gut permeability, fecal dysbiosis, and the subsequent translocation of pathogen-associated molecular patterns (PAMPs, such as LPS) or gut-associated bacteria back into the pulmonary circulation. This review highlights the systemic nature of lung regeneration, which likely depends heavily on intestinal health through the GLA. Ultimately, leveraging these remote microbial networks through precision postbiotic supplementation, dietary priming, or microbiota transplantation represents a crucial frontier in precision medicine to promote definitive alveolar repair.