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.
Highlights
Lead (Pb), a potent environmental toxicant, is ubiquitous in daily life, and poses serious threats to public health
Seven-day oral administration of antibiotics successfully depleted the gut commensals of mice, as indicated by treated mice having a three order of magnitude decrease in their gut microbiota compared to the controls (Supplementary Figure S1C)
We observed that the intestinal absorption and tissue accumulation of Pb were exacerbated in mice lacking intestinal microbiota (Figure 1), suggesting that gut microorganisms can play a role in limiting the bioavailability of Pb
Summary
Lead (Pb), a potent environmental toxicant, is ubiquitous in daily life, and poses serious threats to public health. The effect of Pb on the gut, one of the primary sites of absorption and excretion of metals (James et al, 1985), has received much less attention. Studies on the toxic effects of Pb on intestinal physiology have mainly focused on the following aspects. Histopathological observations have proved that Pb exposure can directly lead to local oxidative stress and inflammation in the gut, and caused marked intestinal morphological disorders (Crespo et al, 2006). Chronic Pb exposure can damage intestinal epithelial cells and tight junction (TJ) function, and perturbs the synthesis and secretion of intestinal mucin, disrupting the physical barrier of the gut (Holcombe et al, 1976; Breton et al, 2013)
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