Oral Supplementation of Lead-Intolerant Intestinal Microbes Protects Against Lead (Pb) Toxicity in Mice

Abstract

Oral exposure to the heavy metal lead (Pb) causes various dysfunctions in animals. However, the influence of gut bacteria on Pb absorption, bioaccumulation, and excretion is largely unknown. In this study, we use a mouse model to investigate the relationship between gut microbiota, Pb-intolerant intestinal microbes and Pb toxicity. First, mice were treated with a broad-spectrum antibiotic cocktail to deplete their gut microbiota, and were then acutely and orally exposed to Pb at 1304 mg/kg for 3 days. Compared to the control mice, antibiotic-treated mice had increased Pb concentrations in the blood and primary organs and decreased Pb fecal concentrations, suggesting that gut microbiota limited the Pb burden that developed from acute oral Pb exposure. Next, three Pb-intolerant gut microbes, Akkermansia muciniphila, Faecalibacterium prausnitzii, and Oscillibacter ruminantium, were orally administered to mice, and their effects against Pb toxicity were evaluated. F. prausnitzii treatment significantly promoted the fecal Pb excretion and reduced Pb concentrations in blood (from 152.70 ± 25.62 μg/dL to 92.20 ± 24.33 μg/dL) and primary tissues. Supplementation with O. ruminantium significantly decreased Pb concentrations in blood (from 152.70 ± 25.62 μg/dL to 104.60 ± 29.85 μg/dL) and kidney (from 7.30 ± 1.08 μg/g to 5.64 ± 0.79 μg/g). Treatment with F. prausnitzii and O. ruminantium also upregulated tight junction (TJ) protein expression and the production of short-chain fatty acids by colonic microbiota, and showed protective effects against liver and kidney toxicity. These results indicate the potential for reducing Pb toxicity by the modulation of gut microbiota.