Methylmercury (MeHg) can magnify through food chains and cause potent neurological problems like Minamata disease. Gut microbes have been found to demethylate MeHg while MeHg can destroy the diversity of gut microbes. Our recent study found that selenite (Se4+) could promote the demethylation of MeHg and regulate the diversity of gut microbes in MeHg-poisoned rats (Minamata disease). Elemental selenium at nano-size (nanoSe) was less toxic than Se4+ with comparable bioavailability. In this study, nanoSe was studied on its demethylation of MeHg and regulation of gut microbes in rats with Minamata disease using Se4+ as a positive control. Rats with Minamata disease were treated with nanoSe or Se4+ every other day for 90 days. Fecal samples were collected on days 8, 30, 60 and 90, and concentrations of Se, Hg and MeHg were measured. The diversity and abundance of gut microbes were determined using 16S rRNA gene profiling. It was found that both nanoSe and Se4+ enhanced the demethylation of MeHg, especially before day 30. The percentage of MeHg (of total mercury) in the MeHg-poisoned group was in the range of 81-105% while it was 23-79% in the nanoSe group and 65-84% in the Se4+ group, suggesting the higher demethylation rate of nanoSe than that of Se4+. Both nanoSe and Se4+ regulated the diversity and abundance of gut microbes at both the phylum and genus rank. Therefore, considering its low toxicity, nanoSe is more desirable in combating Minamata disease. Besides, this study confirmed the new role of Se against MeHg poisoning, i.e. the regulation of gut microbes.

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