insights

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Heavy metals such as arsenic, cadmium, lead, mercury, and nickel are naturally occurring pollutants that are non-biodegradable and persist in the environment. Heavy metals pose a particular threat to human health because they can easily enter the body through the skin, respiratory tract, and gastrointestinal tract and have been associated with several adverse health effects, including immune system suppression, hormonal dysregulation, and gut dysbiosis.^1-2 The presence of heavy metals in the gut is also associated with metabolic dysfunction, increased inflammation, and oxidative stress, mostly reported in acute cases of cadmium and lead toxicity.^1,3

Much of the interaction between metal and host occurs in the gastrointestinal tract, as these environmental contaminants are highly present in water and food sources. A recent study in Poland found that cereals and vegetables were major dietary contributors to daily cadmium, mercury, and nickel exposure, though daily intake levels were still well below guidelines set forth by the European Food Safety Authority.⁴ The study also found that drinking water contributed to 30% of daily lead exposure, and these intake levels straddled the threshold for acceptable daily limit.⁴ Worldwide, there is significant risk for lead toxicity, and for many countries, lead remains a significant health hazard.⁵

As industrial development and modern globalization continue, humans are exposed to increased levels of environmental toxicants—including heavy metals—at varying volumes, concentrations, and complexities. If dietary exposure is a significant part of the equation, can targeting the gut microbiome be a possible solution? Probiotics have a range of demonstrated health benefits in the gut microbiome, and one area of new research is focused on their therapeutic potential for enhancing the detoxification of heavy metals. Several strains of Lactobacillus have demonstrated the capacity to effectively bind to and sequester heavy metals from aqueous solution and in human cell models.^6-8 These studies suggest that beneficial probiotic bacteria may also act to strengthen the intestinal barrier, reducing the absorption and permeability of heavy metal particulates in the gut.^6-8 Subsequent in-vitro and human studies have sought to quantify this effect within the context of a living microbiome, with promising results.

Human Implications for Probiotic Therapies

Reasonable evidence shows that probiotic intervention may reduce serum levels and increase both urinary and fecal excretion levels of various toxic metals in animal models.^8-14 As an additional benefit, gut microbiome sequencing of these subjects showed increased commensal microbial abundance and decreased intestinal permeability.^8-11 Researchers postulate a similar effect in humans: probiotics work to heal the gut and improve microbial conditions. This in turn reduces heavy metal toxicity when exposure occurs and/or this bacterium acts as a therapeutic agent to combat the toxic effect when high levels of heavy metals are present.

Using a Caco-2 model of the intestinal epithelium, researchers hypothesized that Lactobacillus rhamnosus GR-1 may prevent the translocation of cadmium and lead across the intestinal barrier, as previous research found that these bacteria can bind to and excrete these particulates in-vitro. In the cell model, the bacteria sustained its binding profile for 48 hours and significantly reduced concentrations of both metals tested. However, the binding efficiency of the bacteria decreased as more cadmium and lead were absorbed. The bacteria effectively reduced particulate absorption by the cells to prevent basolateral translocation of the metals across the intestinal epithelium.⁷

A preliminary observational study of pregnant Tanzanian women assessed the effect of probiotic supplementation on blood metal levels. During the study, the intervention group was given yogurt containing Lactobacillus rhamnosus GR-1 while the control group was given whole milk or no intervention. In the control group, blood levels of mercury and arsenic continued to increase, but blood metal levels in the probiotic group remained at similar or lower levels.¹⁵ Though limited in scope, this study suggests that probiotic consumption may have a preventive effect against heavy metal toxicity.

Building on the findings from the study in Tanzania, a longer observational trial in China wanted to determine if probiotics had any effect on serum levels of copper and nickel in occupational metal workers. In baseline blood and fecal samples of the metal workers, researchers found elevated levels of copper and nickel as theorized but also noted decreased antioxidant enzyme activity and increased levels of proinflammatory cytokines. In fecal samples, copper and nickel levels of the metal workers prior to the intervention were significantly lower than the control group, suggesting that the changes in metabolic and enzymatic processes due to chronic exposure may inhibit detoxification pathways over time.¹⁶ During the intervention, workers were given a daily 250g dose of probiotic yogurt containing Pediococcus acidilactici GR-1 over 12 weeks. Workers who consumed the probiotic yogurt reported an 18% greater decrease in copper and an 11% greater decrease in nickel levels compared to those who did not. Blood samples of the probiotic group also reported decreased serum levels of malonaldehyde, IL-1β, and IL-6 as well as the increased serum levels of catalase activity, IL-4, and IL-10 at the end of the trial.¹⁶

Bioremediation of Heavy Metal Toxicity

Studies suggest that enhancing microbial conditions in the gut microbiome with probiotics helps to prevent heavy metal particle absorption, translocation, and permeability in the intestinal tract.^6,7,9-11 However, the impact of heavy metal toxicity extends beyond the gut and impacts other organ systems such as the kidneys, liver, and brain.³ Researchers suggest a potential link between dysbiotic gut microbiota and increased heavy metal translocation and bioaccumulation into host tissue.^12-14 When compared to a normal diet control, mice on a high-fat diet accumulated higher amounts of metals in both organs, suggesting that low gut microbial abundance may be a risk factor for tissue damage and increased heavy metal nephro- and hepatoxicity.¹³

Probiotics may enhance enzyme production and efficiency involved in detoxification processes, with some studies suggesting that the bacteria’s modulatory effects on bile acid synthesis is one mechanism that may support the healthy excretion of heavy metals.^8-11 Four separate animal studies have found that Lactobacillus casei SYF-08 and Lactobacillus plantarum CCFM8661 increased biliary glutathione output and fecal bile acid excretion by modulating bile flow and hepatic bile acid synthesis.^8-11 These studies provide preliminary evidence for the role of probiotics in supporting enterohepatic circulation that needs to be further investigated.

Interestingly, in the same studies, a group of mice were given probiotics after an antibiotic pretreatment, and there was no modulatory effect on bile acid noted.^8-11 This suggests that states of dybiosis may limit the overall benefit of probiotics. Supporting the gut microbiome with probiotic bacteria over time allows for greater bacterial colonization, diversity, and abundance to occur.³ Robust microbial communities can improve conditions in the gut to confer a protective effect and, in the presence of heavy metals, may result in greater detoxification capacity.

Clinical Takeaways

Probiotics have a range of demonstrated health benefits in the gut microbiome, and animal studies provide clinical plausibility that probiotic supplementation has the potential to reduce total toxic burden in humans. For patients at occupational or geographical risk of heavy metal exposure, probiotic supplementation may be an effective, preventive dietary approach. Even in small amounts, probiotics conferred some health benefits on diversifying gut microbiota and enhancing detoxification processes. Probiotics can be supplemented or combined with food sources such as yogurt or fermented foods to increase dietary intake. Probiotic supplementation is a cost-effective intervention that presents low risk and may already be part of a patient’s treatment plan.

Learn more about other strategies to support healthy detoxification at IFM’s upcoming Environmental Health Advanced Practice Module (APM).

References

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2. Assefa S, Köhler G. Intestinal microbiome and metal toxicity. Curr Opin Toxicol. 2020;19:21-27. doi:1016/j.cotox.2019.09.009
3. Arun KB, Madhavan A, Sindhu R, et al. Probiotics and gut microbiome – prospects and challenges in remediating heavy metal toxicity. J Hazard Mater. 2021;420:126676. doi:1016/j.jhazmat.2021.126676
4. Koch W, Czop M, Ilowiecka K, Nawrocka A, Wiacek D. Dietary intake of toxic heavy metals with major groups of food products—results of analytical determinations. Nutrients. 2022;14(8):1626. doi:3390/nu14081626
5. Kordas K, Ravenscroft J, Cao Y, McLean EV. Lead exposure in low and middle-income countries: perspectives and lessons on patterns, injustices, economics, and politics. Int J Environ Res Public Health. 2018;15(11):2351. doi:3390/ijerph15112351
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7. Daisley BA, Monachese M, Trinder M, et al. Immobilization of cadmium and lead by Lactobacillus rhamnosusGR-1 mitigates apical-to-basolateral heavy metal translocation in a Caco-2 model of the intestinal epithelium [published correction appears in Gut Microbes. 2019;10(4):553]. Gut Microbes. 2019;10(3):321-333. doi:1080/19490976.2018.1526581
8. Chen Z, Tang Z, Kong J, et al. Lactobacillus casei SYF-08 protects against Pb-induced injury in young mice by regulating bile acid metabolism and increasing Pb excretion. Front Nutr. 2022;9:914323. doi:3389/fnut.2022.914323
9. Zhai Q, Liu Y, Wang C, et al. Lactobacillus plantarum CCFM8661 modulates bile acid enterohepatic circulation and increases lead excretion in mice. Food Funct. 2019;10(3):1455-1464. doi:1039/c8fo02554a
10.  Zhai Q, Liu Y, Wang C, et al. Increased cadmium excretion due to oral administration of Lactobacillus plantarum strains by regulating enterohepatic circulation in mice. J Agric Food Chem. 2019;67(14):3956-3965. doi:1021/acs.jafc.9b01004
11.  Zhai Q, Tian F, Zhao J, Zhang H, Narbad A, Chen W. Oral administration of probiotics inhibits absorption of the heavy metal cadmium by protecting the intestinal barrier. Appl Environ Microbiol. 2016;82(14):4429-4440. doi:1128/AEM.00695-16
12.  Muhammad Z, Ramzan R, Zhang R, et al. Assessment of in vitro and in vivo bioremediation potentials of orally supplemented free and microencapsulated Lactobacillus acidophilus KLDS strains to mitigate the chronic lead toxicity. Front Bioeng Biotechnol. 2021;9:698349. doi:3389/fbioe.2021.698349
13.  Lui T, Liang X, Lei C, et al. High-fat diet affects heavy metal accumulation and toxicity to mice liver and kidney probably via the gut microbiota. Front Microbiol. 2020;11:1604. doi:3389/fmicb.2020.01604
14.  Li B, Jin D, Yu S, et al. In vitro and in vivo evaluation of Lactobacillus delbrueckii bulgaricus KLDS1.0207 for the alleviative effect on lead toxicity. Nutrients. 2017;9(8):845. doi:10.3390/nu9080845
15.  Bisanz JE, Enos MK, Mwanga JR, et al. Randomized open-label pilot study of the influence of probiotics and the gut microbiome on toxic metal levels in Tanzanian pregnant women and school children. mBio. 2014;5(5):e01580-14. doi:1128/mBio.01580-14
16.  Feng P, Yang J, Zhao S, et al. Human supplementation with Pediococcus acidilactici GR-1 decreases heavy metals levels through modifying the gut microbiota and metabolome. NPJ Biofilms Microbiomes. 2022;8(1):63. doi:1038/s41522-022-00326-8