From intestinal barrier to inflammatory response: Combined impact of deoxynivalenol and heat stress in mice.

Heat stress (HS) and deoxynivalenol (DON) are two major stressors that significantly harm animals in livestock production. This research aims to analyze the joint impact of DON and heat stress on the gut health of male mice and to delve into the mechanisms behind it. After establishing a graded heat stress model and determining an appropriate exposure temperature, 48 male ICR (Institute of Cancer Research) mice were randomly allocated to four groups: control group (C), heat stress group (42 °C for 2 h, H), DON exposure group (receiving 2.5 μg DON/kg/day, D), and combined heat stress and DON exposure group (DH). After 14 days of model establishment, duodenal microbiota profiles were analyzed by sequencing, and indicators of duodenal injury were assessed using histological, molecular biological, and immunological methods. The findings showed that simultaneous exposure to DON and heat stress greatly aggravated intestinal harm in mice, as indicated by the shortening of intestinal villi, deepening of crypts, and decreased tight junction protein expression, which results in increased intestinal permeability. Additionally, the combined stress significantly increased the expression of inflammatory factors in the intestine, suggesting that the exacerbated inflammatory response played a pivotal role in aggravating intestinal damage. Mechanistic studies indicated that DON and heat stress alter the gut microbiota, stimulate the NF-κB signaling pathway, and encourage the release of inflammatory factors, indirectly affecting the function of the intestinal barrier. According to our study, the combined effects of DON and heat stress lead to intensified intestinal damage in male mice by impairing the intestinal barrier function and initiating inflammatory response pathways. These discoveries enhance our understanding of how environmental factors affect intestinal health and provide a foundation for developing preventive and therapeutic measures for associated diseases.