Reframing the gut-lung axis: Microbiota dysbiosis, immune-redox regulation, and the potential role of vitamin C.

Abstract

The respiratory system is continuously exposed to environmental antigens, pathogens, and pollutants, requiring tightly regulated immunity to balance inflammation and host defense. Increasing evidence indicates that the microbiome-within the airways and through the gut-lung axis-plays a critical role in shaping pulmonary immune responses. Microbial metabolites such as short-chain fatty acids (SCFAs), tryptophan-derived indoles, and bile acid intermediates, influence the maturation and functional programming of alveolar macrophages, dendritic cells, and T lymphocytes. Using the emerging framework of microbiota dysbiosis-related disorders, this review distinguishes descriptive microbial alterations from functionally and clinically relevant dysbiosis involving microbial metabolites, barrier integrity, immune regulation, and respiratory outcomes. Nutritional and microbiome-targeted interventions-such as dietary fiber, probiotics, and antioxidant micronutrients including vitamin C-may help restore immune homeostasis and reduce inflammatory burden through microbiota-mediated and redox-regulatory pathways. By supporting epithelial barrier integrity, modulating oxidative stress, and promoting regulatory immune signaling, vitamin C may complement microbiome-directed strategies aimed at maintaining respiratory immune resilience. The review critically synthesizes mechanistic, observational, and clinical evidence linking microbiota dysbiosis to respiratory immune homeostasis and evaluates microbiome-targeted and vitamin C-related strategies according to their current level of evidentiary support.