Short-Chain Fatty Acids Mitigate Perinatal Methylmercury-Induced Cognitive Impairment Via Modulation of the Gut...

Methylmercury (MeHg) is a potent neurotoxin that disrupts neurodevelopment in offspring when exposure occurs early in life. However, to date, there is a lack of effective therapeutic strategies for MeHg toxicity. Short-chain fatty acids (SCFAs), metabolites of gut microbial fermentation, influence the gut-brain axis and offer neuroprotective effects. This study investigated the effects of a SCFA intervention on offspring cognitive impairment and gut microbiota dysbiosis following maternal MeHg exposure. The Morris water maze protocol was employed to evaluate cognitive performance in the filial generation of rats. SCFAs were quantified with gas chromatography, while microbial community profiling of the intestine was performed with high-throughput sequencing of the 16 S ribosomal RNA gene. Additionally, histopathological alterations were evaluated via hematoxylin and eosin (HE) staining. The results showed that SCFA supplementation significantly increased mercury excretion through the feces and reduced mercury accumulation in the colon and brain compared to the MeHg group. MeHg exposure markedly decreased colonic levels of acetate, propionate, and butyrate, but SCFA supplementation effectively restored these levels. Further investigations demonstrated that SCFA supplementation influenced the intestinal microbial community and restored its diversity, while HE staining revealed that SCFAs alleviated pathological damage to both the colon and brain tissues. Additionally, behavioral assessments demonstrated that MeHg exposure reduced platform crossings in offspring rats, while SCFA supplementation significantly enhanced cognitive performance. These findings highlight the potential of SCFAs in mitigating MeHg-induced damage and improving cognitive function, offering new insights into therapeutic approaches for neurotoxin exposure.