Cold Exposure-Induced Intestinal Dysfunction: Mechanisms, Animal Models, and Nutritional Intervention Strategies

Abstract

Cold exposure is an important environmental stressor that can disrupt physiological homeostasis and induce complex metabolic, immune, oxidative, and gastrointestinal responses. Increasing evidence indicates that the intestine is a sensitive target of cold exposure, yet the underlying mechanisms and their interrelationships remain incompletely understood. This review summarizes and critically evaluates current evidence on cold exposure-induced intestinal dysfunction and adaptation, with emphasis on intestinal barrier integrity, mucus and digestive function, inflammatory and oxidative responses, pyroptosis-related signaling, gut microbiota remodeling, animal models, and potential intervention strategies. Experimental studies in rodents, pigs, poultry, and fish indicate that cold exposure can induce intestinal morphological alterations, epithelial barrier disruption, increased permeability, tight-junction remodeling, mucus and digestive dysfunction, inflammatory activation, oxidative stress, apoptosis, and, under specific conditions, inflammasome-associated pyroptosis. Concurrent alterations in gut microbial composition and metabolites may interact with epithelial and immune responses, although the temporal and causal relationships among these processes remain insufficiently defined. Importantly, intestinal responses to cold are highly context-dependent and vary according to exposure temperature, duration, pattern, species, nutritional status, acclimation history, and pre-existing disease. Evidence from experimental colitis models further suggests that controlled cold exposure may promote mucosal repair and antimicrobial defense under selected conditions, indicating that cold exposure is not universally detrimental to intestinal health. This review also evaluates nutritional and food-derived strategies, including rutin, plant-derived preparations, dietary glucose, sodium butyrate, vitamin D3, probiotics, prebiotics, and other microbiota-targeted approaches, which have shown potential in mitigating cold-associated intestinal disturbances. Finally, major methodological and translational challenges are discussed, including the need for standardized cold-exposure protocols, causal and longitudinal studies, functional microbiome analysis, and better translation from animal models to human health. Collectively, current evidence supports a multidimensional and context-dependent framework for understanding how cold exposure influences intestinal homeostasis and highlights nutritional and food-derived interventions as promising strategies for maintaining intestinal health under cold environmental conditions.