Nutrition, T-2 Toxin, and Gut Microbiota in Kashin–Beck Disease: Current Evidence and Proposed Links Within the Microbiota–Gut–Osteochondral Framework
TL;DR
KBD-related experimental models provide evidence that selenium deficiency and T-2 toxin exposure can induce osteochondral injury, including combined-exposure effects, and experimental studies also indicate that these exposures can be associated with alterations in gut microbial composition.
Abstract
Highlights What are the main findings? Human studies have identified KBD-associated alterations in gut microbial composition and metabolic profiles, whereas experimental models support the osteochondral effects of selenium deficiency and T-2 toxin exposure. A microbiota–gut–osteochondral framework may provide a biological context linking environmental exposures, host nutritional status, and cartilage injury, although most mechanistic connections remain to be experimentally validated in KBD. What are the implications of the main findings? An evidence-stratified framework helps distinguish direct KBD observations, KBD-related experimental evidence, and hypotheses derived from broader microbiome and skeletal research. Future longitudinal and mechanistic studies integrating microbiome, metabolome, immune profiling, and nutritional assessment are required to clarify causal relationships and evaluate the potential of microbiota- and nutrition-based approaches. Abstract Kashin–Beck disease (KBD) is an endemic osteoarthropathy characterized by the degeneration and necrosis of articular cartilage and epiphyseal growth plate cartilage, with disease onset occurring predominantly during childhood. Its etiology has long been associated with environmental and nutritional factors, particularly selenium deficiency, T-2 toxin exposure, and dietary imbalance. Recent studies have also reported alterations in gut microbial composition and metabolic profiles in patients with KBD, raising the possibility that the gut microbiota may represent an additional component of its multifactorial etiology. This narrative review critically evaluates current evidence linking nutritional factors, T-2 toxin exposure, gut microbial alterations, and osteochondral injury in KBD, with particular attention to the level of evidence supporting these relationships. Direct human evidence is currently limited to a small number of predominantly cross-sectional microbiome and metabolomic studies, largely involving adults with established KBD. KBD-related experimental models provide evidence that selenium deficiency and T-2 toxin exposure can induce osteochondral injury, including combined-exposure effects, and experimental studies also indicate that these exposures can be associated with alterations in gut microbial composition. However, these findings do not demonstrate that gut microbial changes mediate exposure-related osteochondral injury. Proposed pathways involving short-chain fatty acids (SCFAs), intestinal-barrier dysfunction, lipopolysaccharide (LPS)-related inflammatory signaling, immune regulation, and bone remodeling are supported mainly by experimental or mechanistic evidence from non-KBD settings and have not been validated as an integrated causal pathway in KBD. The microbiota–gut–osteochondral framework should therefore be regarded as an evidence-stratified, hypothesis-generating model. Prospective studies in children and adolescents from endemic areas, together with factorial exposure models, direct measurement of proposed intermediate mediators, and functional microbiota-manipulation experiments, are needed to determine whether gut microbial alterations contribute causally to KBD development.