Effects of maternal exposure to 2,6-dichloro-1,4-benzoquinone during pregnancy and lactation on the gut microbiota and neurodevelopment in offspring rats.

Abstract

2,6-dichloro-1,4-benzoquinone (DCBQ), as an emerging drinking water disinfection byproduct, has been widely detected in drinking water and pose potential risks. However, there are relatively few reports on their potential neurodevelopmental toxicity, especially the lack of in vivo studies as the most direct evidence. A rat model was established for the entire gestation and lactation period to study the neurodevelopmental toxicity of DCBQ in offspring rats, through evaluating gut microbiota, neurotransmitters and neurobehaviors. Maternal rats were administered with DCBQ at 0.5, 5, and 50 mg/kg body weight via gavage throughout gestation and lactation. Our results showed that maternal DCBQ exposure induced prolonged neural reflex behavior, decreased motor activity, and increased anxiety-like behavior in offspring rats. And the levels of brain-derived neurotrophic factors and neurotransmitters, especially glutamate and dopamine, in serum and hippocampus were significantly decreased in offspring rats after maternal DCBQ exposure. Maternal DCBQ exposure induced imbalance of intestinal microbiota in a gender-specific way. In addition, maternal DCBQ exposure induced significant changes of 123 metabolites, affecting multiple metabolic pathways, such as mTOR pathway. In particular, the altered gut microbiota showed strong associations with altered metabolites, neurotransmitters and neurobehaviors after maternal DCBQ exposure. Our findings suggest that maternal DCBQ exposure may impair neurodevelopment and disrupt gut microbiota and fecal metabolite profiles of offspring rats, indicating a potential gut microbiota-metabolome-neurochemical link. Our study highlights the importance of evaluating the neurodevelopmental toxicity of disinfection byproducts in future.

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