High-temperature exposure induces neurobehavioral abnormalities in mice through disruption of the gut microbiota.

Rising global temperatures pose significant health risks. However, the neurobehavioral consequences of high-temperature exposure remain undefined. In this study, the C57BL/6J mice were exposed to different temperature levels (26 °C, 38 °C, and 40 °C) for 3, 7, and 14 days. Fecal microbiota transplantation (FMT) was performed to further investigate the role of the gut microbiota. Two-sample Mendelian randomization (MR) analysis was employed to estimate the causal impact of gut microbiota composition on inflammation and neurobehavioral abnormalities. Herein, we found that mice exposed to 40 °C for 14 days exhibited impaired motor coordination and working memory, reduced exploratory behavior, and increased anxiety. Neuronal injuries were also observed in the cerebral cortex and hippocampus, along with structural damage and barrier dysfunction in the ileum and colon. Moreover, high-temperature exposure elicited a significant rise in the level of lipopolysaccharide, a concomitant dysregulation of inflammatory cytokine, and the pronounced activation of NF-κB signaling pathway. FMT from healthy mice ameliorated these adverse effects caused by high-temperature exposure. Although high-temperature reshaped both fungal and bacterial communities, only bacterial dysbiosis correlated with neurobehavioral abnormalities. MR analysis further indicated that gut microbiota perturbations might be linked with the inflammatory responses and neurobehavioral abnormalities. Taken together, these findings suggest high-temperature exposure evokes inflammatory responses and neurobehavioral abnormalities via dysbiosis.