Can beneficial bacteria stop the body from absorbing lead?

Researchers at Worcester Polytechnic Institute (WPI) are exploring an unusual biological strategy to reduce the danger posed by lead exposure: using harmless bacteria inside tiny worms to capture the toxic metal before it can be absorbed. The two-year project, led by associate professor Natalie Farny, has received a $400,753 grant from the National Institutes of Health. Although the work is still at an early experimental stage, it could eventually contribute to probiotic technologies designed to protect people living in environments where lead contamination cannot be removed quickly or completely.

Lead poisoning most often occurs when people swallow contaminated water, food, household dust, or particles of deteriorating paint. Children are particularly vulnerable because their developing nervous systems can be permanently damaged by even relatively small amounts of exposure. Lead can interfere with brain development, learning, behavior, and other physiological processes, and it may enter drinking water when old plumbing systems release the metal into the supply. Current interventions focus primarily on identifying and eliminating the source of contamination. For patients with severe poisoning, doctors may use chelation therapy, in which chemical agents bind lead and help the body excrete it. Such treatment, however, is not generally intended as a routine defense against low-level environmental exposure.

Farny’s team is investigating whether a probiotic bacterium could perform a similar binding function within the gastrointestinal tract. The researchers will concentrate on Escherichia coli Nissle, a nonpathogenic strain used in probiotic products outside the United States to help treat gastrointestinal conditions, including diarrhea. Unlike disease-causing strains of E. coli, Nissle has a long history of use in certain medical and nutritional applications. In the WPI study, the bacterium will be modified to produce aptamers, short strands of DNA or RNA capable of folding into structures that recognize and attach to specific molecules or ions. The central idea is to make the bacteria act as microscopic lead traps while they pass through the digestive system.

The first experiments will be conducted in Caenorhabditis elegans, a soil-dwelling nematode that measures approximately one millimeter in length and feeds on bacteria. C. elegans is widely used in biology because its transparent body, short life cycle, and well-characterized genetics allow scientists to observe biological processes efficiently. Though far simpler than a human, the worm possesses conserved cellular and molecular pathways that can provide an initial indication of whether a biological intervention is toxic, effective, or capable of changing the movement of substances through the gut. Farny’s group will feed the worms engineered bacteria together with lead and then examine whether the metal remains bound within the intestinal contents rather than entering the animals’ tissues.

The proposed mechanism depends on keeping lead chemically sequestered long enough for it to leave the body. Aptamers can be designed or selected to fold into three-dimensional shapes with binding sites that attract particular targets. If the engineered E. coli Nissle produces these molecules in the worm’s gastrointestinal tract, the aptamers could attach to lead ions and reduce their availability for absorption. The researchers will need to determine whether the molecules remain stable in the gut, whether they bind lead strongly in the presence of other minerals and digestive compounds, and whether the bacteria can produce enough aptamer to make a measurable difference. They must also verify that the engineered microbes do not create unintended biological effects.

A second part of the project will use artificial intelligence to search for a potentially simpler route to lead binding. Dmitry Korkin, WPI’s Harold L. Jurist ’61 and Heather E. Jurist Dean’s Professor of Computer Science, will analyze genetic information from E. coli Nissle to identify sequences that might already encode useful metal-binding capabilities. Rather than inserting entirely new genetic material, the researchers hope to rearrange or repurpose existing bacterial code. This approach could reduce the complexity of engineering the organism and potentially simplify later development, although any candidate design would still require extensive laboratory testing for performance and safety.

Korkin describes the process as an iterative discovery loop in which computational predictions guide experiments and experimental results improve subsequent predictions. Machine-learning systems can compare large collections of genetic sequences, identify patterns associated with biomolecule production, and suggest combinations that might generate efficient binding structures. In this project, AI will not replace laboratory validation. Predicted genetic arrangements must be introduced into bacteria, tested under controlled conditions, and evaluated for how strongly and selectively their products bind lead. Results from those experiments can then be fed back into the computational models, allowing researchers to refine the designs over multiple cycles.

The project builds on years of work in Farny’s laboratory, including student-led research supported by early funding from Robert F. Ferrari, a WPI alumnus and president of Northeast Water Solutions, a Rhode Island company specializing in water systems engineering. Farny is a synthetic biologist whose research examines how biological systems can be adapted to address environmental challenges. Her previous work includes research into gene regulation in soil bacteria used in industrial and environmental engineering, supported by a 2024 National Science Foundation CAREER Award. She is also a co-inventor on four patent applications involving aptamers, giving the new project a foundation in both microbial engineering and nucleic-acid-based molecular design.

The researchers emphasize that the work is not yet a treatment for lead poisoning and that results from C. elegans cannot be directly translated into human use. A successful experiment in worms would represent only an early proof of concept. Any future probiotic designed to bind lead would need to undergo studies in more complex animal models, followed by rigorous evaluation of dosage, stability, efficacy, microbial safety, genetic containment, and interactions with the human microbiome. Scientists would also need to establish that captured lead is reliably eliminated rather than merely redistributed within the body. Nevertheless, a living bacterial system could eventually complement environmental remediation by offering temporary protection while contaminated pipes, soil, paint, or water sources are being addressed. The NIH-supported study, funded through the National Institute of Environmental Health Sciences under award R21ES038018, is therefore testing whether engineered microbes can become a new biological tool against one of the world’s most persistent environmental health threats.

Web References: https://www.wpi.edu/people/faculty/nfarny; https://www.wpi.edu/academics/departments/biology-biotechnology; https://web.archive.org/web/20230129015832/https:/www.wpi.edu/people/faculty/dkorkin; https://www.sciencedirect.com/science/article/pii/S1871678424000256; https://wp.wpi.edu/farnylab/; https://www.wpi.edu/news/wpi-researcher-receives-12-million-award-determine-how-environment-impacts-gene-expression-bacteria

References: National Institute of Environmental Health Sciences, National Institutes of Health, award R21ES038018; Worcester Polytechnic Institute research announcement

Keywords

Lead poisoning, engineered probiotics, E. coli Nissle, aptamers, C. elegans, synthetic biology, bioengineering, artificial intelligence, environmental health, public health, gastrointestinal tract, microbial engineering