Metabolic dysregulation reshapes the immune landscape: The gut microbiota-mTOR axis in respiratory viral infection immunity.

Respiratory viral infections pose a significant global public health threat, particularly in individuals with metabolic disorders, who face heightened severe disease risk and attenuated vaccine immune responses due to compromised immunity. This review elucidates how dynamic interactions between the gut microbiota, its metabolites, and the mechanistic target of rapamycin (mTOR) signaling pathway in metabolic disorders exacerbate infection severity and impair vaccine efficacy. Metabolic disorders induce chronic inflammation, gut microbiota dysbiosis, and mTOR hyperactivation, disrupting T and B cell metabolic reprogramming, suppressing antiviral innate immunity, vaccine-induced antibody production, and immune memory, and amplifying cytokine storms and lung injury. The mTOR-microbiota-immune axis serves as a critical nexus of metabolic and immunoregulation in this process. We summarize targeted intervention strategies, including gut microbiota modulation, mTOR inhibitors, and novel vaccine adjuvants, which restore metabolic-immune balance, significantly reducing severe respiratory viral infection morbidity and mortality while enhancing vaccine antibody titers and T cell memory in metabolically compromised populations. These approaches provide a theoretical foundation and clinical guidance for personalized immune interventions.