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Dietary lead modulates the mouse intestinal microbiome: Subacute exposure to lead acetate and lead contaminated soil
S Elizabeth George1, Richard Devereux1, Joseph James1
1U. S. Environmental Protection Agency, Office of Research & Development, Center for Environmental Measurement & Modeling, Gulf Ecosystem Measurement & Modeling Division, Gulf Breeze, FL 32561, United States.
Abstract:
The effect of dietary lead on the intestinal microbiome has not been fully elucidated. To determine if there was an association between microflora modulation, predicted functional genes, and Pb exposure, mice were provided diets amended with increasing concentrations of a single lead compound, lead acetate, or a well characterized complex reference soil containing lead, i.e. 6.25-25 mg/kg Pb acetate (PbOAc) or 7.5-30 mg/kg Pb in reference soil SRM 2710a having 0.552 % Pb among other heavy metals such as Cd. Feces and ceca were collected following 9 days of treatment and the microbiome analyzed by 16 S rRNA gene sequencing. Treatment effects on the microbiome were observed in both feces and ceca of mice. Changes in the cecal microbiomes of mice fed Pb as Pb acetate or as a constituent in SRM 2710a were statistically different except for a few exceptions regardless of dietary source. This was accompanied by increased average abundance of functional genes associated with metal resistance, including those related to siderophore synthesis and arsenic and/or mercury detoxification. Akkermansia, a common gut bacterium, was the highest ranked species in control microbiomes whereas Lactobacillus ranked highest in treated mice. Firmicutes/Bacteroidetes ratios in the ceca of SRM 2710a treated mice increased more than with PbOAc, suggestive of changes in gut microbiome metabolism that promotes obesity. Predicted functional gene average abundance related to carbohydrate, lipid, and/or fatty acid biosynthesis and degradation were greater in the cecal microbiome of SRM 2710a treated mice. Bacilli/Clostridia increased in the ceca of PbOAc treated mice and may be indicative of increased risk of host sepsis. Family Deferribacteraceae also was modulated by PbOAc or SRM 2710a possibly impacting inflammatory response. Understanding the relationship between microbiome composition, predicted functional genes, and Pb concentration, especially in soil, may provide new insights into the utility of various remediation methodologies that minimize dysbiosis and modulate health effects, thus assisting in the selection of an optimal treatment for contaminated sites.
Insights
Dietary lead exposure altered mouse gut microbiome composition and function, increasing metal resistance genes. Lead acetate and soil-lead altered microbial communities differently, impacting potential host health and metabolism.
Area of Science:
- Environmental toxicology
- Microbiome research
- Gut health
Background:
- The impact of dietary lead (Pb) on the intestinal microbiome is not fully understood.
- Lead exposure can occur through various sources, including contaminated soil and food.
Purpose of the Study:
- To investigate the association between lead exposure, gut microflora modulation, and predicted functional genes.
- To compare the effects of lead acetate versus lead in reference soil on the mouse gut microbiome.
Main Methods:
- Mice were fed diets with varying concentrations of lead acetate or lead-contaminated reference soil (SRM 2710a) for 9 days.
- Fecal and cecal samples were analyzed using 16S rRNA gene sequencing.
- Predicted functional genes associated with microbial metabolism and resistance were assessed.
Main Results:
- Lead exposure significantly altered cecal and fecal microbiomes, with distinct changes observed between lead acetate and soil-lead treatments.
- Increased abundance of genes related to metal resistance, siderophore synthesis, and arsenic/mercury detoxification were noted.
- Shifts in bacterial populations, including a decrease in Akkermansia and an increase in Lactobacillus, were observed. Firmicutes/Bacteroidetes ratio changes suggested potential obesity links, while Bacilli/Clostridia increases indicated sepsis risk.
Conclusions:
- Dietary lead exposure, from both pure compounds and complex soil matrices, significantly impacts gut microbiome composition and function.
- Understanding these lead-induced microbiome alterations is crucial for developing effective remediation strategies and mitigating adverse health effects.
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