Certain probiotic bacteria, namely Lactiplantibacillus plantarum LP14, Lactobacillus crispatus LCRO4, and Lactobacillus acidophilus LA12, are able in varying degrees, to detoxify cadmium, lead, and other toxic metals. These microbial allies may also be able to mitigate intestinal epithelial damage caused by heavy metal exposures.

Those are the key signals from a new paper published in Frontiers in Microbiology.  

Though the observations were from in vitro experiments, and not an in vivo human trial, they provide strong proof of concept that certain microbes can sequester and detoxify toxic metals, and that they hold potential for reducing the toxicity associated with heavy metals (HM) we humans absorb via our food and water.

“Taken together, our findings illustrate that probiotic-mediated intestinal bioremediation is a feasible and promising strategy to counteract heavy metal exposure,” says microbiologist Marco Pane, PhD, who was lead investigator on the new study.

Pane is the Chief Science Officer of Probiotical, an Italian company focused on developing probiotic strains for use in human health and nutrition products. Probiotical sponsored the new study, which was done in collaboration with researchers at the University of Ghent, and the University of Piemonte Orientale.

“Taken together, our findings illustrate that probiotic-mediated intestinal bioremediation is a feasible and promising strategy to counteract heavy metal exposure.”

–Marco Pane, PhD, Chief Science Officer, Probiotical

“It is intriguing to note that many L. plantarum strains are reported elsewhere to adsorb and immobilize heavy metals. Our results concur with those reports and even hint that dietary consumption of L. plantarum–rich fermented foods (such as traditional sauerkraut or other lactic-fermented vegetables) alongside a potentially contaminated meal (e.g., a fish dish high in HMs) could help to reduce HM absorption in the gut,” Pane and colleagues write.

Toward Bioremediation

The three organisms–LP14, LA12 and LCR04—analyzed in the current study were chosen based on an earlier in vitro experiment in which each microbe was exposed to a mixture of four HMs, namely cadmium Cd²⁺ (1.1 mg/L), chromium Cr³⁺ (17.6 mg/L), mercury Hg²⁺ (8.8 mg/L), and lead Pb²⁺ (14.9 mg/L). There were two parts to the test: in the first, the bugs were co-incubated with the HM mixture, while in the second they were grown in HM-free media, with the toxin mixture added afterward.

All three of these well-characterized, gut-derived lactobacilli showed the ability to sequester and detoxify the metals to varying degrees. 

For the current experiments, Pane and his research team used the Simulator of the Human Intestinal Microbial Ecosystem (SHIME), which models the conditions inside the human stomach, small intestine, and colon. The SHIME simulator allowed the investigators to test high levels of cadmium, lead, chromium, mercury and other metals that would be toxic to actual humans.

For these tests, the SHIME platform was configurated for a dynamic representation of upper GI tract, followed by a short-term colonic simulation under fed condition. The survival, growth, and heavy metal detoxification capacity of each strain were assessed under sequential gastric, small-intestinal, and colonic conditions.

SHIME enabled Pane and his team to assess and compare the three microbes, and measure their relative affinities for sequestering particular metals. 

Colonic Phase is Key

They found that L. plantarum LP14, and L. crispatus LCRO4 showed strong ability to minimize the bioavailability of the toxic metals, but only in the colonic phase of the SHIME simulator. In contrast, L. acidophilus LA12 showed only a minimal—though measurable—capacity for detoxification.

All three lactobacilli strains maintained high cell counts through the simulated small intestine (bile and pancreatic enzymes), indicating that they could indeed tolerate the biochemical stresses of the small intestinal conditions. But they did not show any HM detoxification activity in the small intestinal part of the simulator.

Mechanistically, only the strains that proliferated well in the colonic phase achieved substantial HM removal.

“For all the strains, quantification analyses revealed that the samples from end-of-ileum-simulating environment displayed highly similar HM levels to the blank conditions (in which the reactor was filled with HMs and to which no bacteria were added), suggesting that small intestine conditions did not enable HM detoxification,” they write.

They add that L. acidophilus LA12, which thrives in small intestinal conditions, did not proliferate well in colonic conditions, which could explain its minimal capacity for metal detoxification.

Metal-Specific Variances

The researchers observed both strain-specific and metal-specific variations. Both LP14 and LCR04 were able to detoxify lead, cadmium, chromium, and lead to some degree. But LCR04 showed a particular affinity for lead, reducing the amount of lead in the supernatant by about 45%. Both microbes were able to reduce cadmium and chromium by 20-40%.

“Mercury was the most recalcitrant metal,” Pane notes. LP14 and LCR04 were only able to detoxify around 10% of the mercury in the test mixture.

It is well-established that HM exposure can adversely impact intestinal mucosal integrity and intestinal homeostasis. Though these effects vary according to metal type and concentration, all heavy metals have an irritating effect on gut epithelium, inducing tissue stress and inflammation, and altering microbiome composition.  

Mucosal Protective Effects

To assess whether the probiotics could, in fact, protect GI mucosa from heavy-metal induced tissue damage, Pane and his group followed their SHIME simulator studies with an experiment using a gut ex-vivo system (GEVS).

This system utilized small intestines excised from freshly killed 13 days-old mice, cultivated in a silicone-based gut ex vivo system, with serum free tissue culture medium. The intestines were passed through six independent chambers, each chamber connected to two needles attached to input/output syringes. This allowed precise control of the flow of a nourishing medium into the inner intestinal compartment.

At high concentrations, heavy metals tend to be extremely disruptive to intestinal mucosa. Pane’s team initially tested the HM concentrations used in the preliminary screening and SHIME experiments, but found that at these levels the metals caused so much damage that the intestinal tissue was no longer viable.

“The probiotic-treated tissues showed a dampened inflammatory response and a preservation of epithelial integrity compared to tissues exposed to HMs alone.”

They ended up testing lower HM concentrations (0.69 mg/L Cd²⁺, 31.2 mg/L Cr³⁺, 5.2 mg/L Hg²⁺, and 6.9 mg/L Pb²⁺), which had a significant impact on mucosal permeability but without destroying tissue viability.

In the mouse ex-vivo intestinal system, even these relatively low concentrations compromised epithelial barrier integrity and triggered pro-inflammatory responses.

Pre-incubation of the HMs with each of the three probiotic strains markedly alleviated these effects, and restored more or less normal intestinal permeability and cytokine profiles.

“The probiotic-treated tissues showed a dampened inflammatory response and a preservation of epithelial integrity compared to tissues exposed to HMs alone.”

This experiment tested a fixed-ratio mixture of metals, and therefore it sheds little light on the specific mucosal effects of any one of them. The experimental design did not allow the researchers to determine if the protective effect was due to the probiotics’ ability to sequester the damaging metals, or whether it was a secondary result of bioactive substances secreted by the microbes that might fortify mucosal barrier function or down-regulate inflammatory signals.

Those questions, says Pane, remain to be explored in future studies.

Chronic HM exposure tends to reduce the relative abundance of Firmicutes and Proteobacteria, while promoting the growth of Bacteroidetes populations. Functionally, these perturbations can negatively affect gut barrier integrity.

Limited though they are, the current observations do show that that probiotics can reduce the toxic impact of HMs on intestinal tissue. Pane predicted that this is, “most likely through decreased metal bioavailability.”

A Bidirectional Relationship

There are a number of mechanisms through which probiotics like the three tested in these studies could mitigate HM toxicity. These include: direct binding of HMs; chelation and complexation; intracellular accumulation; and enzymatic or chemical modification of the metals via oxidation, reduction or demethylation. 

Dr. Pane characterizes the relationship between heavy metal pollutants and the gut microbiota as “bidirectional.”

It is clear that metal exposures can alter both the composition and the function of the microbiome. For example, chronic HM exposure tends to reduce the relative abundance of Firmicutes and Proteobacteria, while promoting the growth of Bacteroidetes populations. Functionally, these perturbations can negatively affect gut barrier integrity, and alter the composition of short chain fatty acids produced by the microbiota.

But, as is shown clearly in Pane’s experiments, certain gut-derived microbes can alter the toxicity of problematic HMs, and reduce their negative impact on intestinal physiology. This is the core principle of bioremediation.

There are obvious limitations to Pane’s studies. Firstly, they are corporate-funded (Probiotical), and may therefore contain biases in favor of the companies patented probiotic strains. Since no other probiotic species or strains were tested, the data cannot be generalized beyond the three strains used in the experiments.

Secondly, these are early-stage, in vitro experiments and not human clinical trials—or even in vivo animal studies. Whether the observed metal-mitigating effects can actually occur in living beings remains to be determined.

Pane acknowledges that, “the absence of in vivo data limits the translational generalizability of the findings, particularly regarding systemic outcomes and long-term efficacy.”

However, he stressed that, “These constraints do not detract from the novelty and relevance of the study but highlight the need for a cautious interpretation.”

“Heavy metal exposure is a chronic public health condition that source control cannot resolve at the population level. Intestinal bioremediation is the missing piece of the food-safety chain,” Dr. Pane said on the NutraIngredients website. “We now have the scientific basis to advance it into clinical research.

In the future, he and his team plan to test probiotic HM remediation in animals, in the hope of confirming the compelling phenomena they observed in the in vitro experiments. The ultimate goal, he says, is to bring this into the clinical real-world as a “more natural, proactive, and less invasive means to diminish the health risks associated with environmental heavy metal burdens.

END