GUT-LUNG, GUT-SKIN, AND MICROBIOTA-EPITHELIUM INTERACTIONS: FUNCTIONAL DYNAMICS OF BARRIER FUNCTION AND IMMUNE RESPONSE

The gut microbiota constitutes a dynamic ecosystem that influences the functions of multiple organ systems through its structural integrity, metabolite production, and modulation of host immunity. The reciprocal interactions among the gut, skin, and lungs are conceptualized as complex axes that operate through barrier integrity, immune responses, and microbial or metabolic signaling. Elucidating the core components of healthy skin and respiratory microbiotas, their contributions to host defense, and their association with epithelial barrier integrity is essential for understanding how gut-derived alterations can impact distant organs. The intestinal epithelial barrier, comprising tight junctions, a mucus layer, and epithelial cells, serves as a primary defense by restricting the translocation of pathogenic microorganisms and harmful metabolites into systemic circulation. Disruption of this barrier permits the entry of bacteria, microbial products, cytokines, and diet-derived molecules into the circulation, thereby initiating inflammatory responses in remote organs, particularly the skin and lungs. Regulatory molecules such as short-chain fatty acids, tryptophan metabolites (notably aryl hydrocarbon receptor ligands), Vitamin D, and neuroendocrine mediators modulate both barrier function and immune responses. Within the gut-skin axis, accumulating evidence indicates that dysbiosis, reduced microbial diversity, decreased short-chain fatty acid levels, and imbalances in specific bacterial species are associated with dermatoses, including atopic dermatitis, psoriasis, rosacea, acne vulgaris, and seborrheic dermatitis. Selected probiotic and prebiotic interventions have been reported to improve disease severity, pruritus, and barrier function. In the context of the gut-lung axis, gut dysbiosis correlates with the development and prognosis of conditions such as pneumonia, viral respiratory infections, asthma, chronic obstructive pulmonary disease, and cystic fibrosis, mediated by epithelial barrier disruption, immune cell migration via homing receptors, microbiota-derived metabolites, and inter-microbial communication. Therefore, gut-focused, microbiota-targeted interventions represent promising complementary strategies for the prevention and treatment of skin and lung diseases.