Pathophysiological Role of Thermoregulatory Reactions in the Development of Common Cold Diseases: Paradigmatic Shift from Pathogen-Centric to Host-Response Model: A Critical Review

This review synthesizes research on the pathophysiological role of thermoregulatory responses in the development of cold-related diseases, focusing on the physiological mechanisms underlying thermoregulation and their interaction with the immune system. Special attention is given to the effects of cold stress on mucosal barriers and systemic effects, the role of gut microbiota in thermoregulation considering age and gender differences, as well as the application of host-responsive models in clinical settings with potential therapeutic approaches. The aim of the review was to evaluate thermoregulatory-immune interactions, analyze the impact of cold stress on mucosal integrity and systemic inflammation, compare age and gender variations in gut microbiota, and identify therapeutic strategies targeting microbiota and immune modulation. A critical analysis of multidisciplinary studies using animal and human models with molecular, immunological, and microbiome profiling was conducted. Results indicate that cold exposure modulates immune cell populations and cytokine profiles, disrupts gut barrier function through changes in tight junctions and inflammatory pathways, and consistently alters gut microbiota diversity with limited research on sex and age effects. Integration of these findings highlights the complex interaction between thermoregulation, immunity, and microbiota in cold-related diseases. These concepts inform the development of targeted clinical interventions and emphasize the need for standardized integrative models.