Engineered Bacteria Detox Mercury from a Fish-Rich Diet

From coal burning to gold mining, human activities have led to widespread mercury pollution in the air. This mercury eventually settles in water, where it transforms into toxic methylmercury (MeHg). MeHg biomagnifies up the food chain, putting top predators like bluefin tuna—and the people who eat them—at risk of mercury poisoning and birth defects, particularly neurodevelopmental disorders.

Current therapies for MeHg toxicity rely on non-specific chelation of metal ions and are effective in acute cases; however, there is a need for more targeted treatments for chronic exposure. In response, researchers have begun exploring native and engineered bacteria as promising tools for mercury detoxification.

Among them is Elaine Hsiao, a biologist at the University of California, Los Angeles, who studies how the maternal microbiome affects fetal brain development. She collaborated with colleagues at the University of California, San Diego, who specialize in MeHg exposure and its accumulation in fish. Together, they engineered a commensal gut microbe capable of detoxifying MeHg. Their findings, published in Cell Host & Microbe, demonstrate that the engineered bacterium can reduce MeHg bioaccumulation in maternal and fetal mice.¹ Building on this work, the team envisions developing a probiotic to help lower mercury-related health risks associated with a fish-rich diet.

“[This work] is really exciting. People have been trying to engineer various metabolic functions into the gut microbiome for a while,” said Timothy Lu, a synthetic biologist and biotechnology entrepreneur, who was not involved in the study. “This application of getting rid of mercury in the diet seems interesting…It’s something the world needs.”

Mercury resistance (mer) genes are largely absent from the microbes present in the human and mouse gut microbiota. Because of this, the researchers turned to gene sequences merA and merB from a mercury-resistant strain of Pseudomonas aeruginosa. These genes demethylate and reduce MeHg. This process generates less harmful compounds like inorganic mercury, which is less readily absorbed and more easily excreted from the body. They integrated both sequences into Bacteroides thetaiotaomicron, a highly prevalent commensal gut bacterium that has proven to be safe as a probiotic.²

To test this engineered strain called Bt^merA/B, the researchers grew the bacterium in media supplemented with either pure MeHg or a bluefin tuna-derived form of MeHg. In both conditions, Bt^merA/B exhibited MeHg demethylation activity while strains lacking the genes could not reduce MeHg.

Then, the researchers colonized germ-free mice with either wild type B. thetaiotaomicron or Bt^merA/B followed by a high oral dose of pure MeHg, since oral ingestion is the main route of exposure. Mice with the engineered bacterium only broke down MeHg in the gut, measured through fecal content; however, the researchers still saw MeHg in other tissues such as the liver or brain.

“We thought that we were overloading them with too much methylmercury because it was still able to get into the bloodstream,” explained Hsiao. Instead, the researchers opted to study its effects through chronic dietary intake. Indeed, mice colonized with the engineered microbe and fed a diet high in bluefin tuna had much lower MeHg levels than expected in the colon and brain. The researchers also saw similar effects when they gave the bacterium as a probiotic to mice with normal microbiomes.

Next, the researchers investigated whether this pattern would also occur in pregnant mice. “This is kind of the most vulnerable population to methylmercury,” said Hsiao. The team examined the effects of toxin exposure to MeHg-rich (tuna), MeHg-modest (salmon), and no MeHg diets during gestation. They found that mice with Bt^merA/B successfully decreased levels of MeHg in both maternal and fetal tissues, and the mice had lowered signs of mercury toxicity in the fetal brain.

In addition, when the researchers profiled the mice’s fetal brain transcriptomes, they saw that Bt^merA/B prevented some of the negative outcomes associated with MeHg, such as gene expression changes related to neurodevelopmental abnormalities. Hsiao remarked, “It was some nice evidence for us that a probiotic given during pregnancy could be a feasible type of intervention even for limiting fetal exposure.”

Jordan Bisanz, a microbiologist at Pennsylvania State University who was not involved in the research, said “[The study’s] idea here, is acting at the critical juncture. If there's going to be mercury in the tuna, it's very hard to get the mercury out of the tuna,” He added that by using B. thetaiotaomicron as a platform, “if you can intercept the mercury before it enters the bloodstream or affects the host, it’s a key window in which an intervention could be successful, which is a very different way of thinking about bioremediation.”

Still, Hsiao noted that there is more wiggle room—such as modifying other proteins, regulatory genes, or even creating a cocktail of microbes—to improve this approach. Lu shared this view, expressing interest in exploring whether the treatment remains stable within the human microbiome and whether a bacterial consortium might produce a stronger effect. Drawing a comparison, Hsiao added that the ultimate goal would be to develop a probiotic that could help mitigate the risks associated with a seafood-heavy diet.