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.

Assessment of Pb(II), Cd(II), and Al(III) Removal Capacity of Bacteria from Food and Gut Ecological Niches: Insights into Biodiversity to Limit Intestinal Biodisponibility of Toxic Metals

“…Indeed, binding isotherms in the Langmuir model showed that the maximum binding capacity ( Q max ) was high for both boiled (dead) and live forms of two probiotic strains ( Lactobacillus rhamnosus and Propionibacterium freudenreichii ) [ 36 ]. Other researchers have demonstrated that dead and live bacteria have similar binding capacities for Pb and for Cd [ 32 , 36 , 41 , 42 ]. However, live forms are slightly more effective for Pb removal as a result of cell-specific intracellular metal accumulation [ 62 , 63 ].…”

“…Indeed, microbes interact (by biotransformation or sequestration) with metals in the gut, and thus can actively or passively, control bioaccessibility and the further bioavailability of heavy metals [ 30 ]. In experiments on germ-free mice [ 2 , 31 ] or involving broad-spectrum antibiotics [ 32 ], we and others have previously highlighted the gut microbiota’s overarching role as a barrier to heavy metal dissemination. However, not all bacteria have the same ability to limit the bioavailability of toxic metals.…”

“…[ 40 , 41 , 42 ]), dairy propionibacteria, and bifidobacteria [ 38 , 43 ] have been analyzed in separate, heterogenous studies. Furthermore, non-LAB have rarely been screened for these properties: only a small number of proteobacterial species ( E. coli ) and gut-isolated anaerobic bacteria ( Akkermansia muciniphila , Faecalibacterium prausnitzii , and Oscillibacter ruminantium single strain isolates) have been studied [ 32 , 43 ]. Other genera with notable in vitro detoxification potential (such as Pseudomonas , Stenotrophomonas , or Bacillus ) are not appropriate for targeting the intestinal compartment.…”

“…Various selected food-sourced microbes can prevent the absorption of heavy metals in the gut (and thus dissemination into the tissues) and thus enable their excretion in the feces. The efficacy of this approach has been demonstrated in preclinical studies of acute and chronic Pb [ 32 , 44 , 45 ], Cd [ 46 , 47 ], and Al [ 48 , 49 ] toxicity in the mouse.…”

Effets des polluants environnementaux et alimentaires sur le microbiote intestinal

“…Les fonctions en lien avec les voies métaboliques énergétiques, celles des lipides et des acides biliaires se trouvent également fortement perturbées. Certaines bactéries intestinales possèdent cependant des capacités à séquestrer le plomb ; d'autres peuvent avoir des rôles protecteurs -lorsque administrées en tant que probiotiques -non seulement sur la physiologie digestive mais aussi sur la toxicité vis à vis d'autres organes tels que le foie et les reins [52].…”