Tebuconazole mediates cognitive impairment via the microbe-gut-brain axis (MGBA) in mice

Tebuconazole, one of the most widely used triazole fungicides, is reported to potentially pose a risk of inducing neurological disorders in human beings. Considering the increasing exposure, whether it could influence cognitive function remains to be elucidated. Herein, we used a mouse model to evaluate the potential cognitive risks and possible mechanisms from the continuous edible application of tebuconazole at low concentrations. Our study revealed that tebuconazole deteriorated spatial learning and memory and downregulated the expression of glutamate receptor subunits. Importantly, metagenomic analysis indicated that tebuconazole not only led to significant shifts in the composition and diversity of the gut microbiota but also changed intestinal homeostasis. Specifically, after exposure, tebuconazole circulated in the bloodstream and largely entered the gut-brain axis for disruption, including disturbing the Firmicutes/Bacteroidetes ratio, interrelated neurotransmitters and systemic immune factors. Moreover, pretreatment with probiotics improved immune factor expression and restored the deterioration of synaptic function and spatial learning and memory. The current study provides novel insights concerning perturbations of the gut microbiome and its functions as a potential new mechanism by which tebuconazole exposes cognitive function-related human health.