Probiotic Alleviate Fluoride-Induced Memory Impairment by Reconstructing Gut Microbiota in Mice

Abstract BackgroundFluoride which is widespread in our environment and food due to geological origin and industrial pollution has been identified as developmental neurotoxicants. Gut-brain axis provide new sight to the brain-derived injury. We hypothesized that fluoride-induced memory impairment was associated with gut dysbiosis, which could be prevented by improving the gut microbiota. MethodsMice were given fluoridated drinking water (sodium fluoride, 100 mg/L) for 70 days and administered with PBS or a probiotic strain, Lactobacillus johnsonii BS15 for 28 days prior to and throughout a 70 day exposure to sodium fluoride. ResultsResults showed that fluoride reduces the exploration ratio in Novel object recognition (NOR) test and the spontaneous exploration during the T-maze test in mice following an hour water avoidance stress (WAS), which were significantly improved by the probiotic. 16S rRNA sequencing showed a significant seperation in ileal microbiota between the fluoride-treated mice and control mice. Lactobacillus was the mainly targeting bacteria and significantly reduced in fluoride-treated mice. BS15 reconstructed the fluoride-post microbiota and increased the relative abundance of Lactobacillus. D-lactate contant and diamine oxidase (DAO) activity, two biomarkers of the gut permeability were reduced in the serum of probiotic-inocluated mice. ZO-1, an intestinal tight junction protein, which was reduced by fluoride in mRNA and protein levels were increased by the probiotic treatment. Moreover, in the hippocampus which is essential to learning and memory, the probiotic increased the down-regulated mRNA levels of myelinassociated glycoprotein (MAG) level, Bcl-xl and decreaed up-regulated mRNA levels of Bad in fluoride-treated mice. The probiotic applied in this study also increased down-regulated mRNA and protein levels of brain-derived neurotrophic factor (BDNF) and cAMP response element-binding protein (CREB), and balanced the inflammatory cytokines in mRNA and protein levels in hippocampus of fluoride-treated mice. ConclusionsThese results suggested that there may be some correlations between the fluoride-induced memory dysfunction and alteration of gut microbiota, and reconstruction of gut microbiota is a potential method to prevent the memory dysfunction.