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Methylmercury (MeHg) is a ubiquitous environmental toxicant with neurotoxic effects. Although its neurotoxicity had been more studied, the role of gut microbiota remains unclear. In this study, adult zebrafish and larvae were exposed to MeHgCl at the dose of 0, 1 and 10 ng/mL. MeHgCl exposure impaired the locomotor activity via upregulation of apoptosis and autophagy related genes in the brain. Intestinal and cerebral metabolome indicated that phosphatidylinositol signaling system and inositol phosphate metabolism pathways were significantly impacted in adult zebrafish upon MeHgCl exposure. The levels of myo-inositol (MI) in the intestine and brain were decreased and positively correlated. 16 S rRNA sequencing data from adult zebrafish showed that MeHgCl exposure also shifted the structure of gut microbiota and reduced the relative abundance of Bacteroidetes and Proteobacteria, which were further identified at genus level as Aeromonas and Cetobacterium. Further functional analysis indicated that MeHgCl disrupted inositol phosphate metabolism of gut microbiota. Notably, MI supplementation restored the impairment of locomotor activity and inhibited the upregulation of apoptosis and autophagy related genes, such as bcl-2 and atg5. Thus, this study not only revealed the key role of gut microbiota in MeHgCl-mediated neurotoxicity but also gave new insights into antagonizing its toxicity. Copyright © 2020 Elsevier Inc. All rights reserved.

Citation

Jun Zhu, Lei Tang, Shanlei Qiao, Lijuan Wang, Yiming Feng, Li Wang, Qian Wu, Ping Ding, Zhan Zhang, Lei Li. Low-dose methylmercury exposure impairs the locomotor activity of zebrafish: Role of intestinal inositol metabolism. Environmental research. 2020 Nov;190:110020

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PMID: 32777273

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