High-temperature exposure impairs cognitive function by disrupting the gut-brain axis: Evidence from human and rat studies

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BACKGROUND: To investigate the impact of high temperature (HT) exposure on cognitive function in humans and rats, focusing on the gut-brain axis as a potential mediating pathway. METHODS: The study population was derived from the Guangzhou Nutrition and Health Study, with cognitive function assessed using the Addenbrooke's Cognitive Examination Revised (ACE-R) scale. HT exposure was defined as exposure for more than one year during the career. In animal experiments, 36 male Sprague Dawley rats were exposed to controlled temperatures (25°C, 30°C, 35°C, and 40°C) for four hours daily over 15 days. Cognitive function was evaluated using the Morris Water Maze (MWM) test. Neurodegeneration, glial activation, neuroinflammation, intestinal barrier function and inflammation were evaluated by Western blot, Elisa, immunohistochemistry and immunofluorescence staining. 16S rRNA sequencing was employed to profile the gut microbiota. Targeted metabolomics analysis was conducted using gas chromatography-mass spectrometry to quantify short-chain fatty acids (SCFAs) in fecal samples. RESULTS: Human participants in the HT group exhibited significantly lower ACE-R and memory scores compared to controls. Similarly, HT exposure in rats led to a notable decline in spatial learning and memory, accompanied by damage to hippocampal neurons. Further examinations revealed that HT exposure disrupted intestinal homeostasis, characterized by a reduced abundance of SCFA-producing bacteria and decreased SCFA levels in the intestines. This disruption was accompanied by intestinal inflammation, compromised intestinal barrier integrity, and neuroinflammation. CONCLUSION: This study suggests that HT exposure may negatively impact cognitive function through mechanisms potentially involving the gut-brain axis, offering insights into possible underlying biological pathways.

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