A Pathogen Is Persisting in Infant Formula. UMD Researchers Found Genetic Clues to Explain Why

Cronobacter sakazakii has made international headlines following recalls of powdered infant formula. To better understand the pathogen’s persistence and transmission, UMD researchers used AI to conduct the first genomic meta-analysis of strains from all over the world.

University of Maryland researchers are shedding new light on how a dangerous foodborne pathogen may have adapted to thrive in dried and powdered foods across the global supply chain. Their study, recently published online in the International Journal of Food Microbiology, could transform how we monitor and prevent contamination in critical food products like powdered infant formula.

Cronobacter sakazakii has made international headlines in recent years following recalls of powdered infant formula and has been linked to life-threatening infections in premature infants, the elderly and other vulnerable populations. Although infections are rare, the consequences can be devastating—ranging from meningitis to long-term developmental issues.

To better understand the pathogen’s persistence and transmission, the researchers conducted the first genomic meta-analysis of C. sakazakii bacteria strains from all over the world. Using an AI large language model (LLM) to standardize data from massive and inconsistent collections, and machine learning to identify potentially significant genes.

“We’re seeing how certain accessory genes—those not essential to survival but beneficial under specific environmental conditions—could confer advantages that help Cronobacter sakazakii persist in food systems and possibly even resist sanitation protocols,” said Ryan Blaustein, an assistant professor of Food and Nutrition Science and senior author of the study.

Other team members include two department colleagues, Professor Abani Pradhan and Postdoctoral Associate Maurui Gao. Their work was supported in part through a grant from the U.S. Department of Agriculture National Institute of Food and Agriculture.

Individuals of a species carry a core set of genes that are shared across the species. But different strains or variants from different regions contain additional accessory genes unique to that strain. Blaustein and his colleagues analyzed 748 whole genome sequences collected from food, clinical and environmental sources across North America, Europe and Asia to identify the most complete set of C. sakazakii genes—also known as a pangenome—to date.

The LLM standardized inconsistent metadata about the origins and sources of each sample, among other things, making large-scale comparison possible.

“Everyone enters things differently, from the date and time to things like ‘powdered infant formula” using a capital “P” or lowercase “p” or just powdered formula or even PFI,” said Blaustein, who is a member of UMD’s Center of Excellence in Microbiome Sciences. “We used the language model to recategorize everything that was already in the public database and assign it with a very high accuracy. That hadn’t been done in this setting before.”

Once the team had standardized the data, it used machine learning models to identify core genes and paint a clearer picture of how the accessory genes varied among samples from different locations, environments and conditions. This helped them identify genetic signatures associated with where and how the sample was taken.

They found that samples from powdered foods (including infant formula and powdered milk) relative to other types had larger genomes, and a higher frequency of genes involved in DNA recombination, repair and desiccation resistance, all of which could contribute to the bacterium’s survival in dry conditions. In addition, there was a greater prevalence of genes associated with higher virulence in strains that were likely to persist in the food chain and cause illness.

The team also found correlations between geographic regions and genes associated with formation of biofilms and resistance to heavy metals like copper that show up in some food systems as a component of pesticides or as an essential nutrient, but can also act as an antimicrobial at high levels.

The presence of so many accessory genes with potentially adaptive traits may be what enables C. sakazakii to persist across a variety of ecological niches, including hospitals, food facilities and dried food products. Understanding which genes support C. sakazakii‘s survival in a variety of environments could help target sanitation measures and guide the development of safer processing protocols and technologies. The findings also raise important considerations for the food industry, especially manufacturers of powdered foods.

Importantly, this study provides a pathway to identify genes with key traits of interest for a variety of pathogens. The integration of AI models to clean, standardize and interpret genomic and epidemiological data could help create faster, more accurate molecular surveillance systems for emerging pathogens.

This research underscores the need for international cooperation in understanding how foodborne pathogens evolve and move through the food system, the researchers say. With food products routinely crossing borders and oceans, tracking genetic markers of virulence and resistance has never been more critical.

Story by Kimbra Cutlip for Maryland Today

Yarwood Helps Lead UMD Center of Excellence in Microbiome Sciences

Stephanie Yarwood, a professor of environmental science and technology at the University of Maryland (UMD), recently sat down to discuss her role co-leading the UMD Center of Excellence in Microbiome Sciences.

Launched in February 2023 with startup funding from the University of Maryland Grand Challenges Grants program, the center joins faculty, postdoctoral scholars and graduate students across campus in pursuit of a deeper understanding of complex microbial communities, and how those microbiomes interact with each other and with our ecosystem.

Yarwood is one of the grant’s principal investigators, the other being Mihai Pop, a professor of computer science. In addition to Yarwood and Pop, the center currently has 14 other core members that hail from the College of Agriculture and Natural Resources; the College of Computer, Mathematical, and Natural Sciences; the A. James Clark School of Engineering; and the United States Department of Agriculture (USDA).

Yarwood’s research is focused on soil and how the microorganisms in it help carry out crucial processes to life on Earth, like releasing nutrients for plants to grow, filtering water, and composing antibiotics. She also examines wetland restoration from the perspectives of mitigating climate change and improving sustainable agriculture. 

As someone who has been active in research related to the microbiome for 14 years since coming to UMD, Yarwood is pleased that the center provides a hub to build a consistent community of scientists across campus, collaborating on microbiome research and scholarship that was previously fractured among individual departments and labs.

Since measuring microbiome function requires expensive lab equipment, sharing infrastructure is a key part of that community building, says Yarwood. Now that equipment can be better shared among researchers in the center, plans are in the works to expand its capacity to help accommodate postdocs and early career scientists who might not be able to afford the lab equipment they need right off the bat.

“If there’s a piece of equipment that you just would like to try and see if it applies to your work, this is part of why we’re here, in order to share that equipment, knowledge and expertise,” she says.

Another one of the center’s strengths, says Yarwood, is supporting student researchers in a more purposeful way than just financially. For example, through its fellowship program, graduate students receive not only an $8,000 stipend, but also participate in hands-on workshops designed to train them to conduct research and communicate across interdisciplinary divides.

Since the center’s inception, faculty have curated a list of more than a dozen courses from across several departments that relate to the microbiome sciences, with discussions in the works to develop a certificate program at UMD.

Now that the community of microbiome researchers on campus is becoming more cohesive, the center is also looking to grow partnerships in the region, adds Yarwood. So far, the center has hosted two annual symposiums that have drawn more than 100 regional scientists.

Another goal on the horizon is to expand the center’s financial support.

“It’s been very generous that the University of Maryland has been able to support the center,” says Yarwood. “Now we have a desire to try to find sustainable funding going forward, potentially private donors to support our work to build the next generation of microbiome scientists.”

Story by Maria Herd, UMIACS communications group

Fellowship Program Builds Bridges in Microbiome Sciences

Microbes quietly shape our world, influencing everything from the air we breathe to the food we eat. Despite their vast impact, research into microbial systems has long been fragmented—split across academic disciplines and institutional silos.

A fellowship program at the University of Maryland is underway to bridge those gaps.

Now in its second year, the Microbiome Center Fellowship brings together eight graduate students from across campus to collaborate on research spanning human, environmental and agricultural microbiomes.

The seven-month program fosters interdisciplinary connections and prepares students to tackle global challenges with a systems-level approach to microbiome science. Fellows receive an $8,000 stipend and gain access to shared computational and sequencing resources, including those at the University of Maryland Institute for Advanced Computer Studies.

The program is coordinated by the UMD Center of Excellence in Microbiome Sciences, which began operations in 2023 with startup funding from the UMD Grand Challenges Grant program.

“Microbes are everywhere, from human and animal health to agriculture and the environment,” says Gabi Steinbach, associate research scientist and program coordinator of the center. “Different habitats host diverse microbes that make up complex microbiomes, and microbes move between these environments, linking them together.”

Steinbach notes a unique aspect to the fellowship: students’ advisers joining in on the networking and community-building activities, creating additional opportunities for cross-disciplinary connections among both faculty and students.

“We’re building a community where students not only gain technical skills, but also learn to work across cultural and disciplinary divides,” Steinbach says.“They get to connect with faculty and peers from diverse fields, which is essential for advancing microbiome science.”

For example, at a recent launch meeting, fellows, their advisers, and program leaders took part in activities designed to spark collaboration—including a research and resource-sharing speed chatting session that participants found both productive and fun.

This year’s Fellows include Raunak Dey and Nakia Fallen from the College of Computer, Mathematical, and Natural Sciences; Claire Barlow from the School of Public Health; Darby Steinman, Ingrid Roselyne Dukundane and Yuzhu Mao from the A. James Clark School of Engineering; and Erin Harrelson and Yue Jiang from the College of Agriculture and Natural Resources.

Throughout the program, these students will participate in team science training, cross-disciplinary workshops, and seminars aimed at preparing them to collaborate across disciplines and translate scientific principles into transformative action. The Fellows will also organize and host an invited panel in December, choosing a topic themselves based on what they have explored together throughout the fellowship. The capstone event will be open to the campus community and will showcase the collaborative outcomes of the program.

“We’re excited to see how these students take what they’ve learned and shape the future of microbiome science,” Steinbach says. “Their panel in December will showcase the kind of innovative, cross-disciplinary thinking we need to solve complex challenges.”

—Story by Melissa Brachfeld, UMIACS communications group

Zierden Receives NSF CAREER Award To Address Women’s Health Disparities

A University of Maryland (UMD) chemical engineer developing specialized therapies for women’s health was named a recipient of the National Science Foundation’s Faculty Early Career Development Program (CAREER) Award—making a step forward in addressing gaps in gynecological care. 

Hannah Zierden, an assistant professor of chemical and biomolecular engineering at UMD, will lead a new initiative that integrates research and education to advance knowledge of the female reproductive tract. The NSF CAREER award is her latest recognition for this ongoing work. 

“I am incredibly honored to receive the NSF funding support for our work, and excited to begin diving into our hypotheses in hopes of uncovering mechanisms that drive female reproductive health,” said Zierden.

The assistant professor will investigate the vaginal microbiome—a home for living bacteria in the female reproductive system—which is responsible for promoting the overall health in this tract, hoping to understand how new treatments could evolve from biological systems. 

She will focus on studying bacterial extracellular vesicles (bEVs), which are biological nanoparticles released by bacteria that enable cell communication between bacteria and host cells, with potential implications for female reproductive diseases. How bEVs come to form is unknown, and there is generally limited knowledge surrounding their fate and function within the female reproductive tract. These limitations slow progress towards treatments for infertility, preterm birth, and sexually transmitted infections. Zierden’s goal is to understand how bEVs impact women’s health throughout the lifespan.

Given what researchers understand about bEVs, these organisms are a growing area of interest as a therapeutic technology given their physical properties. In other words, bEVs could someday be used to deliver treatments within the female reproductive tract.  

“The human body sends a wide variety of signals to coordinate biological functions. Some of those signals are sent by bacterial cells–including bacteria in the female reproductive tract. While bEVs have gotten a lot of attention in recent years, bEVs from vaginal bacteria have been largely neglected,” explained Zierden, who is also a member of the UMD Center of Excellence in Microbiome Sciences. “If we can understand the interactions between bEVs and female reproductive tract cells, we will build a foundation for using bEVs as a potential therapeutic for women’s health,” she said.  

The educational portion of the initiative aims to spark interest in the microbiome sciences within pre-college student populations. In collaboration with the Baltimore Underground Science Space, Zierden will establish an internship program for students from local community colleges. She will also recruit high school students to her lab to provide them with experiential learning opportunities while working towards her research goal. 

“Zierden’s innovative approach to investigating drug delivery in the vaginal microbiome is a testament to her dedication and to our department’s commitment to advancing women’s health,” said Peter Kofinas, Chair of the Department of Chemical and Biomolecular Engineering. “We look forward to seeing the impact of her work, which has tremendous potential to reshape how we think about gynecological care and inspire the next generation of engineers.”

Story by A. James Clark School of Engineering

Congressional Leaders Visit Ghodssi’s MATRIX Lab

MATRIX Lab Director of Remote Sensing and Microsystems Justin Stine (left) explains the work on ingestible capsules going on in the building’s new Advanced Manufacturing Lab.

The Maryland Autonomous Technologies Research Innovation and eXploration (MATRIX) Lab hosted part of a Congressional visit to Southern Maryland by U.S. Senator Chris Van Hollen and U.S. Representatives Steny Hoyer and Sarah Elfreth. On May 19, the members of Congress, plus U.S. Senator Angela Alsobrooks, toured the Naval Air Station Patuxent River, the USMSM SMART Building, and the MATRIX Lab at the University of Maryland (UMD) to learn about how different sectors collaborate to teach students in-demand skills, strengthening the region’s workforce and its economy.

“I am proud of our outstanding federal and state representatives for all they do to provide access and opportunities for our students across the state of Maryland,” said Reza Ghodssi, Distinguished University Professor of Engineering at UMD, a member of the UMD Center of Excellence in Microbiome Sciences, and the Executive Director of Research and Innovation at the MATRIX Lab. “Education and research are always the backbones of what makes the U.S. the world’s leader in science and technology. Thank you to Senator Van Hollen, Representative Steny Hoyer, and Representative Sarah Elfreth for touring the MATRIX Lab during their visit to Southern Maryland and meeting our students and researchers.”

At the MATRIX Lab, representatives from organizations presented examples of how academia, military, government, industry, and nonprofit organizations collaborate to create opportunities in Southern Maryland.

Speakers represented USMSM, the Southern Maryland Navy Alliance (SMNA), St. Mary’s County Economic Development, the Patuxent Partnership, UMD, and the College of Southern Maryland (CSM).

These organizations and many more work together to promote STEM education through field trips, camps, and other activities and give students the hands-on experience they need to succeed through apprenticeships and internships. The organizations also strengthen the technical workforce through promoting educational and professional pathways and creating lifelong learning and development opportunities. When all of these sectors are in constant communication, they empower the community with in-demand skills that real-world employers are looking for.

After the briefings, the members of Congress toured the lab spaces and were able to meet and speak with the researchers and students using the building’s state-of-the-art facilities and cutting-edge equipment.

“The UMD MATRIX Lab is a national leader in research and innovation and an important driver of economic growth and workforce development across Southern Maryland,” said Senator Van Hollen from Maryland’s 8th District. “Seeing their work firsthand and hearing from students and researchers about its impact is not only inspiring, but also highlights the power of partnership in the region between academic institutions, the military, and across the public and private sectors. I’ll continue working to support the critical work being done by UMD and its partners.”

Representative Hoyer of Maryland’s 5th District appreciated the collaboration across sectors that he witnessed on the tour.

“Ensuring Maryland and America stay competitive in the 21st-century global economy requires encouraging academia, government, and the private sector to collaborate together more closely than ever before. I was pleased to see that cooperation at work in Southern Maryland,” he said. “The researchers and innovators at the UMD MATRIX Lab and its partner institutions are helping our state and country get ahead, which is why I will continue to do everything I can to support their vital work.”

Representative Elfreth of Maryland’s 3rd District was impressed at the innovative research coming out of Ghodssi’s lab.

“The innovation at the UMD MATRIX Lab is second to none,” she said. “Senator Van Hollen, Congressman Hoyer, and I had the opportunity to meet with their scientists and learn more about their groundbreaking research on ingestible capsules, autonomous aerial refueling, underwater systems, and more. In Congress, Team Maryland will continue to advocate for university research funding to keep our state at the forefront of research and innovation.”

Story by A. James Clark School of Engineering

Maryland Academy of Sciences Names Hannah Zierden Outstanding Young Engineer

Hannah Zierden, an assistant professor in the Department of Chemical and Biomolecular Engineering, was named the Maryland Academy of Sciences’ Outstanding Young Engineer for her advancements towards specialized nanotechnologies for female reproductive health.

Zierden’s distinction comes from her commitment to one of the most pressing and underserved fields of human medicine, where disparities in funding resources and specialized clinical trials have historically slowed new avenues to enhance women’s health. She followed the footsteps of her graduate mentor, Laura Ensign, and became the second in the department to earn this recognition.

“Many of the Maryland Academy of Sciences awardees are researchers whose work I admire and respect. I am honored to be among them, and have big shoes to fill. I hope to inspire the next generation of engineers and scientists in the coming decades,” said Zierden.

Her pioneering work in therapies for gynecological patients began as a graduate student at Johns Hopkins University, where, after identifying inconsistencies with established models, she developed an animal model to mimic inflammation-induced preterm birth. Her work established an important tool to observe uterine contraction mechanisms via rodents, which resulted in a first-author publication in the American Journal of Pathology, and a Career Development Travel Award from the National Institutes of Health to present her discovery in the Society for Reproductive Investigation Annual Meeting in 2019.

Using this model, Zierden engineered a novel combination nanotherapy for preterm birth prevention. Her work was the first reported evidence of success in preclinical trials for a condition with no treatment approved by the U.S. Food and Drug Administration. This groundbreaking work led to two publications in Science Translational Medicine and Frontiers in Cellular and Infection Microbiology during her graduate studies.

In her short time at Maryland, she has earned affiliations with the university’s Fischell Department of Bioengineering, the Robert E. Fischell Institute for Biomedical Devices, and the Center of Excellence in Microbiome Sciences. Looking ahead, her work seeks to understand how cells communicate in order to shy away from traditional synthetic drugs—developing biological treatments for gynecological patients that may suffer from infertility conditions, bacterial vaginosis, preterm birth and pelvic inflammatory disease, among others. She aims to bridge the gap in specialized treatments for the female reproductive tract for the generations to come.

“As a woman and a mother of a daughter, I hope that women’s health in the coming decades isn’t at a significant disparity when compared to other medical implications. I am working to make sure that my daughter’s reproductive health won’t suffer from a lack of treatment options,” she said.

This article was originally published by the UMD Clark School of Engineering

UMD Researchers Demonstrate Control of Living Cells With Electronics

E.coli bacteria and an electronic device might seem to have little in common, but in a recent experiment, University of Maryland researchers linked them into the first closed-loop system able to communicate across the technological-biological divide.

A team from the Robert E. Fischell Institute for Biomedical Devices and the Institute of Bioscience and Biotechnology Research (IBBR) used chemical reactions and genetic engineering to demonstrate how electronic signals can control the biological processes of cells in real time in a paper recently published in Nature Communications.

The research—led by bioengineering Professor and Fischell Institute Director William E. Bentley and IBBR Research Professor and Fischell Institute Fellow Gregory F. Payne—could be the first step toward developing translatable “smart” health care devices, such as drug-delivery systems for diabetics or real-time trackers of disease progression in cancer patients. (E. coli was chosen because it is an easy-to-propagate microorganism frequently used in experiments.)

The two researchers have been working jointly to advance bioelectronics for years. They say that while devices such as defibrillators and electrocardiograms, which work with electrical signals from the heart, mark great advancements in bioelectronics, there remains a gap in simple devices that access molecular information for health metrics and disease treatment—a gap that their recent progress may begin to address.

“A longstanding impediment to commercialized bioelectronics technology is the ability to successfully establish a seamless connection between biological systems and electronic devices,” said Bentley, who is also a member of UMD’s Center of Excellence in Microbiome Sciences. “As with so many complex relationships, the core of the solution requires good communication—the successful exchange of information.”

In conventional electronics, a flow of electrons through wiring and circuitry carries information, while electromagnetic waves do the work in wireless communications.

“In biology, there aren’t free electrons moving through your body,” said Sally Wang Ph.D. ’23, a postdoctoral researcher and co-lead author on this paper with Chen-Yu Chen Ph.D. ’23, a fellow researcher in Bentley’s lab. “So what do biological systems do to move those electrons? They transfer electrons using redox reactions.”

Cells make redox (or reduction-oxidation) molecules, which can transport electrons from one place to another using redox chemical reactions, causing the gain and loss of electrons in cells. This electron transfer results in changes to oxidation levels in cells and is central to important biological processes like photosynthesis and respiration.

Nearly six years ago, Bentley and Payne demonstrated that redox reactions can bridge the gap between biological and electronic systems; they have since worked to engineer and manipulate biological redox networks for bioelectronic information transfer at multiple levels, including proteins, individual cells and groups of cells. This multifaceted and interwoven connection between systems is what the team has coined the “Internet of Life.”

Building on this research, Wang and Chen demonstrated a closed-loop system where a cell’s biological activity can not only be monitored in real-time using electronic signals, but its genetic systems can also be electronically controlled. The latter function is referred to as “electrogenetics,” an approach that the UMD team introduced and that has since been adopted by several groups worldwide.

Using the gene editing tool CRISPR, the team engineered E. coli bacterial cells to include proteins and antibodies from other organisms such as jellyfish and Pseudomonas bacteria to enable E. coli to respond in a specific way to electricity: When they receive electrons, they project fluorescence as optical signals that can be recorded and interpreted by a machine in real time. The machine can then assess whether it needs to supply more current in order to sustain the transfer of electrons between systems, demonstrating a cycle.

The engineered cells can accept electrons from electrodes as well as from cells via redox reactions, making them in effect “bilingual.”

“This opens doors for building completely new ways to connect information and data-rich technologies to biology,” said Bentley. “There are myriad opportunities that could emerge from electrogenetics.”

In addition to health care innovations—for instance, a self-regulated device connected to the body that monitors a disease and precisely administers drugs—the technology has potential applications in agriculture and environmental conservation as well. A “smart” farmland monitor, for example, could telemetrically provide information about how to optimize the microorganism content in soil, suggesting how much pesticide and herbicide to use and when.

Other authors of this study include Fischell Institute researchers John R. Rzasa, Chen-Yu Tsao, Eric VanArsdale Ph.D.’22 and Fauziah Rahma Zakaria ’25 and IBBR members Jinyang Li Ph.D. ’20 and Eunkyoung Kim.

—This story was originally published by Maryland Today

University of Maryland Hosts Microbiome Research Symposium

More than 70 people braved stark wintry conditions on January 16 to attend a research symposium at the University of Maryland that explored the world of complex microbial communities.

The Symposium on Microbiome Research at the Interface of Environment, Health and Agriculture joined researchers from the federal government, academia and private industry who are focused on the connectivity between microbes interacting with each other, the environment, agricultural systems, and human and animal health.

Hosted by the University of Maryland Center of Excellence in Microbiome Sciences, the event featured multiple talks, breakout sessions, an engaging poster session, and a networking reception. All the events went off without a hitch, despite 4 inches of snow that closed the university for the day and made travel difficult.

“We were fortunate that more than two-thirds of the people who registered were able to show up and participate,” says Mihai Pop, a UMD professor of computer science who is the director of the microbiome center. “We were particularly pleased by the strong turnout from federal scientists in the region, as well as colleagues from the medical and dentistry schools in Baltimore.”

A morning keynote talk by Susannah Tringe, division director of the DOE Joint Genome Institute at the Lawrence Berkeley National Laboratory, looked at the sequence-based interrogation of soil microbiomes, and how those microbes can benefit various ecosystems.

The afternoon keynote by Joff Silberg, a professor of biosciences at Rice University, was presented virtually as Silberg was unable to fly out of Houston due to poor weather. His talk explored the use of engineered living microbes, and how they might be used to monitor various soil pollutants in real time.

Other talks included how microbial communities can impact coffee growers, the effect of cow manure microbes on farm soil, microbial activity related to women’s gynecologic health, and other topics focused on human gut bacteria and inflammatory bowel disease.

“There’s such a rich diversity of perspectives and ongoing work at the University of Maryland involving microbiome sciences,” says Hannah Zierden, an assistant professor of chemical and biomolecular engineering at UMD and core member of the microbiome center. “I’m excited at the opportunities we have and look forward to continued collaborations—as well as new ones—as we expand our outreach and impact.”

Zierden presented some recent research from her own UMD lab at the conference, which aims to better understand the function of bacterial extracellular vesicles produced by vaginal microbes, and how they might be used to engineer biocompatible therapies for healthy pregnancies.

A large contingent of researchers from the University of Maryland School of Dentistry were onsite for the symposium, including Areej Alfaifi, a doctoral student in the dental biomedical sciences program.

“This event broadened my perspective by introducing me to entirely different aspects of microbiome studies,” says Alfaifi, whose dissertation explores the use of genomic sequencing tools to gain a deeper understanding of the oral microbiome in COVID-19 patients. “Connecting with students and faculty from different schools was an amazing experience that reshaped my thoughts on the field. This meeting was truly unforgettable!”

Additional attendees included faculty, postdocs and graduate students from the University of Delaware, Towson University, University of Maryland School of Medicine, and the University of Maryland, College Park.

Federal scientists in attendance hailed from the USDA, FDA, Department of Energy, and the Smithsonian National Zoo, with representatives from QIAGEN, CosmosID—both major sponsors of the symposium—also present.

The symposium also received support from the University of Maryland Institute for Advanced Computer StudiesMid-Atlantic Microbiome Meet-up, and the UMD’s Grand Challenges Grants program.

Pop said the UMD microbiome center will help coordinate another symposium in 2025 in Baltimore, working closely with the Institute for Genome Sciences at the University of Maryland, Baltimore to investigate new topics related to microbiome sciences.

“We expect to continue our momentum in this area, which reaches across multiple scientific, medical and policy-related disciplines,” Pop says. “Our belief is that the basic unresolved questions involving microbial communities are interrelated—and so are the solutions we’re working on.”

—Story by Maria Herd, UMIACS communications group

What Makes Urine Yellow? UMD Scientists Discover the Enzyme Responsible

 

Researchers at the University of Maryland and National Institutes of Health have identified the microbial enzyme responsible for giving urine its yellow hue, according to a new study published in the journal Nature Microbiology on January 3, 2024.

The discovery of this enzyme, called bilirubin reductase, paves the way for further research into the gut microbiome’s role in ailments like jaundice and inflammatory bowel disease.

“This enzyme discovery finally unravels the mystery behind urine’s yellow color,” said the study’s lead author Brantley Hall, an assistant professor in the University of Maryland’s Department of Cell Biology and Molecular Genetics. “It’s remarkable that an everyday biological phenomenon went unexplained for so long, and our team is excited to be able to explain it.”

When red blood cells degrade after their six-month lifespan, a bright orange pigment called bilirubin is produced as a byproduct. Bilirubin is typically secreted into the gut, where it is destined for excretion but can also be partially reabsorbed. Excess reabsorption can lead to a buildup of bilirubin in the blood and can cause jaundice—a condition that leads to the yellowing of the skin and eyes. Once in the gut, the resident flora can convert bilirubin into other molecules.

“Gut microbes encode the enzyme bilirubin reductase that converts bilirubin into a colorless byproduct called urobilinogen,” explained Hall, who has a joint appointment in the University of Maryland Institute for Advanced Computer Studies and is a core faculty member in the Center for Bioinformatics and Computational Biology and Center of Excellence in Microbiome Sciences. “Urobilinogen then spontaneously degrades into a molecule called urobilin, which is responsible for the yellow color we are all familiar with.”

Urobilin has long been linked to urine’s yellow hue, but the research team’s discovery of the enzyme responsible answers a question that has eluded scientists for over a century.

Aside from solving a scientific mystery, these findings could have important health implications. The research team found that bilirubin reductase is present in almost all healthy adults but is often missing from newborns and individuals with inflammatory bowel disease. They hypothesize that the absence of bilirubin reductase may contribute to infant jaundice and the formation of pigmented gallstones.

“Now that we’ve identified this enzyme, we can start investigating how the bacteria in our gut impact circulating bilirubin levels and related health conditions like jaundice,” said study co-author and NIH Investigator Xiaofang Jiang. “This discovery lays the foundation for understanding the gut-liver axis.”

In addition to jaundice and inflammatory bowel disease, the gut microbiome has been linked to various diseases and conditions, from allergies to arthritis to psoriasis. This latest discovery brings researchers closer to achieving a holistic understanding of the gut microbiome’s role in human health.

“The multidisciplinary approach we were able to implement—thanks to the collaboration between our labs—was key to solving the physiological puzzle of why our urine appears yellow,” Hall said. “It’s the culmination of many years of work by our team and highlights yet another reason why our gut microbiome is so vital to human health.”

The scientific finding has garnered national media attention from CBS News, the Washingtonian, and WTOP News.

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This article was adapted from text provided by Brantley Hall and Sophia Levy.

In addition to Hall, UMD-affiliated co-authors included Stephenie Abeysinghe (B.S. ’23, public health science); Domenick Braccia (Ph.D. ’22, biological sciences); biological sciences major Maggie Grant; biochemistry Ph.D. student Conor Jenkins; biological sciences Ph.D. students Gabriela Arp (B.S. ’19, public health science; B.A. ’19, Spanish language), Madison Jermain, Sophia Levy (B.S. ’19, chemical engineering; B.S. ’19, biological sciences) and Chih Hao Wu (B.S. ’21, biological sciences); Glory Minabou Ndjite (B.S. ’22, public health science); and Ashley Weiss (B.S. ’22, biological sciences).

Their paper, “Discovery of a gut microbial enzyme that reduces bilirubin to urobilinogen,” was published in the journal Nature Microbiology on January 3, 2024.

This research was supported by the NIH’s Intramural Research Program, the National Library of Medicine and startup funding from UMD. This article does not necessarily reflect the views of these organizations.