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Posts Tagged ‘College of Medicine and Life Sciences’

Study Finds Gut Bacteria Can Make Blood Pressure Medication Less Effective

A new study from The University of Toledo College of Medicine and Life Sciences has shown gut bacteria can reduce the effectiveness of certain blood pressure drugs.

The research, published this month in the journal Hypertension, offers the first clues to what has been an elusive mystery — why do some people not respond well to medication?

“High blood pressure is often called a silent killer because it doesn’t usually cause symptoms. However, there is a big population of individuals who know they have hypertension but still cannot get it under control, even though they’re taking blood pressure drugs,” said Dr. Tao Yang, an assistant professor in the Department of Physiology and Pharmacology and the study’s first and lead author. “Addressing this is of huge clinical importance.”

Hypertension, or high blood pressure, is a major risk factor for heart disease and stroke, two of the leading causes of death in America. It’s also one of the most common chronic conditions in the United States, with nearly half of U.S. adults considered hypertensive under current guidelines.

Among those with high blood pressure, an estimated 20% have what’s known as resistant hypertension, meaning their blood pressure remains high despite aggressive treatment.

“The only thing doctors can really do in these patients is adding or switching medications and increasing the dose with the hope they can find something that works,” Yang said. “Until now, we haven’t had any clear indication what the mechanism is for resistant hypertension. Our research could provide a first step toward identifying new ways to effectively overcome treatment-resistant hypertension.”

In recent years researchers have more intently examined the link between an individual’s blood pressure readings and the unique collection of bacteria that lives in their gut.

That work — significant portions of which has been done at UToledo — has helped to unravel potential causes of hypertension that extend beyond diet and exercise. However, Yang’s research is the first to examine the impact of gut bacteria on blood pressure medication itself.

Dr. Bina Joe, Distinguished University Professor and chair of the UToledo Department of Physiology and Pharmacology, and the study’s senior author, said the research is a significant extension of UToledo’s work to better understand the causes of hypertension and find new ways to treat it.

“Yang pioneered this important, highly translational idea during his training as a postdoctoral fellow in my laboratory,” she said. “This is now a major research theme in his own laboratory at The University of Toledo.”

In the study, UToledo scientists compared the effectiveness of the antihypertensive drug quinapril in rats with normal gut bacteria against those whose gut microbiota had been depleted by high doses of antibiotics.

Researchers found a clear difference between the two, with animals that were given antibiotics first responding much better to quinapril.

Analysis of the gut bacteria composition in the animals identified the bacteria Coprococcus as the culprit. Laboratory experiments proved that Coprococcus comes, a dominant bacteria species in this genus, can break down quinapril and ramipril, resulting in the compromised blood pressure-lowering effects.

While the UToledo study was limited to animal models and lab experiments, researchers identified at least one intriguing case study that seems to bolster the argument that this finding could be applicable to humans.

That 2015 report, published in the International Journal of Cardiology, described a woman with a long history of treatment-resistant hypertension whose blood pressure was controlled without any antihypertensive medication for the two weeks she was taking antibiotics for a post-surgical infection. Her blood pressure was able to be controlled with only one medication for six months after stopping antibiotics before again becoming treatment-resistant.

“This is just one report and more research is needed. However, this suggests that gut bacteria can play a very real and very important role in regulating the efficacy of blood pressure medication,” Yang said.

The research group plans to continue its work by studying the interaction between additional blood pressure medications and other common types of gut bacteria.

Though long-term use of antibiotics isn’t a realistic strategy for addressing treatment-resistant hypertension, Yang said it should be possible for someone to alter their microbiota through probiotics, prebiotics and changes in diet.

“The ultimate goal of my research is to identify ways we can specifically target the bacteria in an individual’s gut to improve drug efficacy,” he said. “This has the potential to benefit a lot of people.”

Dr. Young Oh, a program officer with the National Heart, Lung, and Blood Institute, agrees that this study represents an important piece of the puzzle in understanding resistant hypertension. The study was supported in part by the NHLBI, part of the National Institutes of Health.

“The gut microbiome has been understudied as it relates to hypertension,” said Oh, who was not a member of the study team. “While this study fills an important knowledge gap, more studies are needed, particularly in humans, to confirm the findings.”

The research was also supported in part by a grant from the American Heart Association.

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Research reported in this release was supported in part by the National Heart, Lung, and Blood Institute (NHLBI), part the National Institutes of Health, under the following grant numbers: R01HL143082 and HL132448.

DISCLAIMER:  The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.


UToledo Scientist Developing Single Drug to Treat Diabetes, Osteoporosis

When Dr. Beata Lecka-Czernik joined The University of Toledo College of Medicine and Life Sciences in 2007, her field was seen by many as something of a curiosity.

A professor in the Department of Orthopaedic Surgery with a joint appointment in the Department of Physiology and Pharmacology, Lecka-Czernik studies the connection between bone health and metabolic processes, including disorders such as diabetes.

“At that time, there were very few people believing there even was an intersection,” she said. “It was novel research, but it has really made a lot of progress with time.”

Dr. Beata Lecka-Czernik

Much of that progress has come from her own lab, which has made key discoveries about how some drugs used to treat diabetes can accelerate bone loss, and how a protein called PPAR-gamma that helps regulate insulin sensitivity also plays a role in the formation of new bone.

This fall, Lecka-Czernik received a five-year, $3.4 million grant from the National Institute on Aging to continue her work that’s ultimately aimed at developing a single therapeutic that could both normalize glucose levels and improve the mass and quality of bone.

Osteoporosis and Type 2 diabetes are both widespread in the United States. The National Institutes of Health estimates that 26 million Americans have Type 2 diabetes and twice that many either have or are at high risk of developing osteoporosis.

What’s more, weak bones and diabetes are often seen together. Lecka-Czernik said research has shown that diabetics suffer twice as many bone fractures as individuals without diabetes.

Her research team, which includes scientists from the Scripps Research Institute, will focus on better understanding the mechanisms of how processes in the bone are integrated with regulation of energy metabolism as they work to fine-tune an experimental drug they previously developed.

That compound, which has been patented by Scripps and UToledo, was found to be effective at regulating glucose and strengthening bone in a 2016 study published in the journal EBioMedicine.

Far from serving as a static scaffolding that supports our bodies, bones are constantly changing. One type of cell breaks down old bone and another type of cell creates new bone.

“You can think of it almost like a road crew,” Lecka-Czernik said. “One crew tears up the old pavement and the next crew comes along to lay new blacktop. In normal situations, they are coupled. As we age the destruction crew speeds up but the paving crew slows down, particularly in post-menopausal women.”

Most of the available therapeutics aimed at improving bone quality focus on slowing down resorption, or the process that breaks down old bone.

There is a relatively new drug that helps activate the cells responsible for building new bone by inhibiting the protein sclerostin, but Lecka-Czernik said some scientists have concerns that this drug may have a negative effect on the vascular system.

By targeting PPAR-gamma, which controls the expression of sclerostin, the experimental therapeutic she and her collaborators are investigating potentially gets around that concern.

And unlike some other insulin synthesizers that have been shown to speed up bone loss, the group’s experimental drug appears to do the opposite — building up healthier, stronger bones.

“If you have one pill that can take care of two pathologies which are common and often seen together, that could have a big impact for health. It could also have an economic impact, especially for the elderly who are spending a lot of money on prescription drugs,” she said. “Thirteen years ago, this was science fiction. Now it seems like a real possibility.”


UToledo Develops Experimental Rheumatoid Arthritis Vaccine

Researchers at The University of Toledo have developed an experimental vaccine that shows significant promise in preventing rheumatoid arthritis, a painful autoimmune disease that cannot currently be cured.

The findings, detailed in a paper published in the journal Proceedings of the National Academy of Sciences, represent a major breakthrough in the study of rheumatoid arthritis and autoimmune diseases in general.

One of the most common autoimmune diseases, rheumatoid arthritis occurs when the body’s immune system attacks and breaks down healthy tissue — most notably the lining of joints in the hands, wrists, ankles and knees.

Dr. Ritu Chakravarti sits behind a microscope

Dr. Ritu Chakravarti

Some estimates suggest rheumatoid arthritis affects as much as 1% of the global population.

“In spite of its high prevalence, there is no cure and we don’t entirely know what brings it on. This is true of nearly all autoimmune diseases, which makes treating or preventing them so difficult,” said Dr. Ritu Chakravarti, an assistant professor in the UToledo College of Medicine and Life Sciences and the paper’s lead author. “If we can successfully get this vaccine into the clinic, it would be revolutionary.”

Chakravarti has for years studied a protein called 14-3-3 zeta and its role in immune pathologies, including aortic aneurysms and interleukin-17— a cytokine associated with autoimmune diseases. Based on their prior work, the research group was focused on the protein as a potential trigger for rheumatoid arthritis.

Instead, they found the opposite.

Rather than preventing rheumatoid arthritis, researchers discovered that removing the protein through gene-editing technology caused severe early onset arthritis in animal models.

Working under a new theory that the 14-3-3 zeta protein protects against rheumatoid arthritis, the team developed a protein-based vaccine using purified 14-3-3 zeta protein grown in a bacterial cell.

They found the vaccine promoted a strong and immediate — but long-lasting — response from the body’s innate immune system, providing protection against the disease.

“Much to our happy surprise, the rheumatoid arthritis totally disappeared in animals that received a vaccine,” Chakravarti said. “Sometimes there is no better way than serendipity. We happened to hit a wrong result, but it turned out to be the best result. Those kinds of scientific discoveries are very important in this field.”

In addition to suppressing the development of arthritis, the vaccine also significantly improved bone quality — a finding that suggests there should be long-term benefits following immunization.

Currently, rheumatoid arthritis is treated primarily with corticosteroids, broad scale immunosuppressive drugs or newer, more targeted biologics that target a specific inflammatory process.

While those therapeutics can alleviate pain and slow the progression of the disease, they also can make patients more vulnerable to infection and, in the case of biologics, can be costly.

“We have not made any really big discoveries toward treating or preventing rheumatoid arthritis in many years,” Chakravarti said. “Our approach is completely different. This is a vaccine-based strategy based on a novel target that we hope can treat or prevent rheumatoid arthritis. The potential here is huge.”

Researchers have filed for a patent on their discovery and are seeking pharmaceutical industry partners to support safety and toxicity studies in hopes of establishing a preclinical trial.


UToledo Infectious Disease, Virology Experts to Discuss COVID-19 at Virtual Town Hall

Faculty from The University of Toledo College of Medicine and Life Sciences will participate in a virtual town hall discussion, “UToledo Experts Address COVID-19: Updates and Vaccine Information,” from 5:30 to 6:30 p.m. on Thursday, Dec. 17, via Webex.

The event hosted by the University of Toledo Foundation is free and open to the public, though registration is required.

Presenters include:

• Saurabh Chattopadhyay, assistant professor of medical microbiology and immunology;

• Joan Duggan, infectious disease specialist and professor of medicine;

• Jennifer Hanrahan, infectious disease specialist and associate professor of medicine;

• Jason F. Huntley, associate professor of medical microbiology and immunology; and

• R. Travis Taylor, assistant professor of medical microbiology and immunology.

Dr. Christopher Cooper, dean of the College of Medicine and Life Sciences and executive vice president for clinical affairs, will lead the discussion.


UToledo Awarded $1.1 Million Federal Grant to Advance Clean Water Technology

Searching for new ways to address the growing threat to drinking water in northwest Ohio and across the globe, Dr. Jason Huntley discovered that native freshwater bacteria can destroy toxins produced during harmful algal blooms.

The University of Toledo scientist has now received a $1.1 million grant from the National Oceanic and Atmospheric Administration to advance that research into real-world solutions.

Huntley, an associate professor in the UToledo Department of Medical Microbiology and Immunology, has already shown in lab experiments that biofilters using those Lake Erie bacteria can remove microcystin at levels exponentially above current exposure guidelines established by the World Health Organization.

“This grant will enable us to extend our research to the next level,” Huntley said. “We did this successfully in the lab. Now we want to scale it up and put the bacteria to work in the water treatment plant.”

Huntley

The three-year research project will take a multifaceted approach to translate Huntley’s earlier finding into technologies that safeguard the drinking water of hundreds of thousands of people.

“One of our big pushes here at UToledo is to not just do science for science’s sake, but to ask questions about how it can improve human health,” Huntley said. “This isn’t just a Toledo problem. There are harmful algal blooms all across the country and all across the world. This is a solution to a global health problem.”

Water treatment plants primarily use activated carbon to capture the microcystin toxins released during some harmful algal blooms. While effective, there are drawbacks. It can be expensive, there’s a limit to how much toxin can be removed from the water and the process generates microcystin-laden waste products that have to be dealt with.

Huntley and his research team believe their bacteria could help address those issues. Biofilters could be used to treat drinking water before it reaches the tap, and the bacteria could be added to the treatment plant byproducts to degrade the lingering toxins.

It’s also an inexpensive solution.

“It’s not free, but it’s really cheap to grow these bacteria that chew up and degrade the toxins. We grow them in water, that’s it. We think we can use them to treat water coming into the treatment plant as well as eliminating toxins in the water treatment byproducts, eliminating the need to incinerate these waste products or send them to a landfill,” Huntley said.

Prior to large-scale testing at the Toledo wastewater treatment plant, researchers will work to further develop and test the biofilters in a range of conditions, such as different water pressures and temperatures.

The research team also will work to isolate and identify the bacterial enzymes that break down microcystin, with a goal of being able to produce them on an industrial scale. Some of that work will be done in collaboration with the Lawrence Livermore National Laboratory — a connection that was made during 2019’s National Lab Day at UToledo. The long-term goal is to develop water treatment tablets or droplet bottles that could be used to quickly detoxify water while boating, at family cabins or while hiking.

Huntley’s early work on this issue was funded by the Ohio Department of Higher Education’s Harmful Algal Bloom Research Initiative and the Ohio Sea Grant. The success of that research helped UToledo earn the NOAA grant.

“This is turning taxpayer money here in Ohio to federally funded grants that bring big money back to Ohio,” Huntley said.


Altered sense of taste present in half of COVID-19 cases

Nearly half of individuals who contract COVID-19 experience changes in their sense of taste, a new analysis led by a University of Toledo researcher has found.

The systematic review, published in the journal Gastroenterology, could provide yet another diagnostic hint for clinicians who suspect their patients might have the disease.

“Earlier studies didn’t note this symptom, and that was probably because of the severity of other symptoms like cough, fever and trouble breathing,” said Dr. Muhammad Aziz, chief internal medicine resident at UToledo and the paper’s lead author. “We were beginning to note that altered or lost sense of taste were also present, not just here and there, but in a significant proportion.”

Aziz and his research collaborators analyzed data from five studies conducted between mid-January and the end of March. Of the 817 patients studied, 49.8% experienced changes to their sense of taste. Researchers suspect the true prevalence could be even higher because some of the studies were based on reviews of patient charts, which may not have noted every symptom.

“We propose that this symptom should be one of the screening symptoms in addition to the fever, shortness of breath and productive cough. Not just for suspected COIVD patients, but also for the general population to identify healthy carriers of the virus,” Aziz said.

Prior research has found that a significant number of people who have COVID-19 don’t know they’ve been infected and may be spreading the virus.

Aziz and his research collaborators suspect an altered sense of taste is more prevalent in patients with minor symptoms, though more studies are needed to validate that suspicion. Even so, changes in an individual’s sense of taste could be a valuable way to identify carriers who are otherwise mostly asymptomatic.

Taste disorders are tied to a variety of viral illnesses. The review did not attempt to identify the reason that COVID-19 is causing changes in patients’ sense of taste; however, researchers theorize it could be COVID-19’s ability to bind to what’s known as the ACE-2 receptor, which is expressed in epithelial cells on the tongue and mouth.

Because the novel coronavirus was unknown prior to its emergence in January, scientists have been moving rapidly to learn more about both the virus and the disease it causes.

Aziz said the drip of new information shows the need for more scientists to dig into the impacts of COVID-19.

“A lot of things are being missed, which is why I think researchers from every field should try to look into this and see if it’s affecting their specialty in one way or another,” he said. “Who knows what systems this virus is affecting. If we can catch it earlier in the disease course, we can prevent the spread of the virus and potentially have ways of managing it.”


UToledo med, nursing students get option to graduate early

In response to the unprecedented public health crisis brought about by the COVID-19 pandemic, The University of Toledo is allowing more than 275 medical and nursing students the option of graduating early.

Students in the College of Medicine and Life Sciences and College of Nursing who have completed all course work, met their degree requirements and been approved for early graduation are eligible to receive their diploma starting as soon as April 17.

Students not graduating early will receive their diploma at UToledo’s previously scheduled virtual commencement ceremonies, which are May 9 for the College of Nursing and May 15 for the College of Medicine and Life Sciences.

The option for early graduation was approved Monday by The University of Toledo Board of Trustees with the support of President Sharon L. Gaber and Provost Karen Bjorkman.

“The College of Medicine and Life Sciences is committed to responding to the COVID-19 pandemic,” said Dr. Christopher Cooper, dean of the UToledo College of Medicine and Life Sciences. “We are proud of our graduating medical students that will be joining residency programs in our region and across our nation. These soon-to-be young doctors will play an important role in meeting people’s healthcare needs.”

In order for a fourth-year medical student to graduate early, they must also enter their residency program early. After receiving their diploma, they must apply for and receive a medical license in the state in which they will be practicing.

Nearly half of UToledo’s fourth-year medical students matched with residency programs in Ohio. Students also matched in some of the hardest hit states, including New York, Michigan and California.

Nursing graduates also have the ability to quickly begin practicing. The state of Ohio recently updated its regulations to allow newly graduated nurses to receive a temporary license before taking the national standardized licensure examination which has been delayed due to the pandemic. The state of Michigan has taken similar steps.

“The COVID-19 pandemic has created a huge need for nurses, both in our region and across the country,” said Dr. Linda Lewandowski, dean of the College of Nursing. “Many of our students have expressed interest in getting out into the field ahead of the predicted surge to help relieve the strain on our healthcare system. These students are ready to practice now, and we’re proud of their eagerness to make a difference.”


UToledo medical students learn residency placements via virtual Match Day event

A total of 165 fourth-year medical students at The University of Toledo learned their residency placements Friday during a live-streamed, virtual Match Day event.

The annual Match Day celebration is a highly anticipated moment for medical students in the UToledo College of Medicine and Life Sciences and at medical schools across the country. Soon-to-be physicians discover at the same moment where they will spend the next three to seven years in residency as they train in their chosen specialties.

Under normal circumstances, students gather together in person with family and friends to share the experience of learning the next step in their careers. However, because of the ongoing COVID-19 pandemic and the need to limit large gatherings, UToledo celebrated the 2020 Match remotely.

“We know this is a very important time in the lives of our students, and one they expected to spend with friends and colleagues as they take one of the final steps before going out into the community as physicians,” said Dr. Christopher Cooper, dean of the College of Medicine and Life Sciences. “We worked very hard to create something special despite the difficult realities we’re living with right now. We are so proud of this class of fourth-year students who will soon be providing care in the communities in which they’ll be practicing.”

In addition to the 165 who learned their Match on Friday, two individuals had already matched with the U.S. Armed Forces, bringing the grand total to 167.

The number of students who matched with The University of Toledo College of Medicine and Life Sciences residency programs increased 30% over the previous year, while the total number of students staying in the greater northwest Ohio increased nearly 50% over the 2019 match.

“We are delighted so many of our students will be staying in our region as they begin their careers as physicians,” Cooper said. “One of our key missions is to provide a pipeline of well-trained, well-qualified physicians to care for our region’s health. It’s encouraging to see such a large increase in the number of students who matched in northwest Ohio.”

Among the other institutions where UToledo students will do their residency work are Yale, Brown, Emory, Duke, the University of Chicago, the University of Michigan, the Mayo Clinic, and the Cleveland Clinic.


Hussain lecture to chart transformation of medical science

The great Greek physician Galen of Pergamon was one of the most influential forces in medical history, with his theories informing the profession for centuries.

Unfortunately, many of Galen’s ideas were wrong.

“For nearly 2,000 years we were practicing medicine like it was the stone age. There was nothing scientific about it,” said Dr. Syed Tasnim Raza, a cardiothoracic surgeon and associate professor of surgery at Columbia University Medical Center.

Thankfully real scientific discovery eventually won out, helping to lead medicine into the cutting-edge field it is today.

Raza, who has spent the last decade studying the history of medicine after more than three decades as a heart surgeon in Buffalo, N.Y., will outline those radical changes at the 11th annual S. Amjad Hussain Visiting Lecture in the History of Medicine and Surgery at 5 p.m. Thursday, Oct. 17.

Dr. Syed Tasnim Raza

The lecture, to be held in Health Education Building Room 110 on UToledo Health Science Campus, is free and open to the public. RSVPs are requested; email hscevents@utoledo.edu or call 419.383.6300.

One of Galen’s primary mistakes was assuming the anatomy of animals he dissected was wholly applicable to humans. For 1,300 years, no one dared question him.

“The thinking was, ‘If Galen said it, it has to be true,’” said Raza. “We need to have the strength to challenge conventional wisdom, dogma and current thinking to improve and continue to change.”

The S. Amjad Hussain Visiting Lecture in the History of Medicine and Surgery was created in honor of Hussain, professor emeritus of cardiovascular surgery and humanities, emeritus member of the UToledo Board of Trustees, and columnist for The Blade.

“Dr. Tasnim Raza has had a deep interest in the history of medicine and has just finished a book manuscript on the history of heart surgery. He is a man who is well versed in not only in the subject of surgery, but also in the arts and humanities,” Hussain said. “The study of history of medicine is important because it shows us the distance we have covered and the path we have traversed to reach the present. History being a continuum, we cannot chart a future unless we know the past.”

In part, the lecture series helped further inspire Raza’s interest in the history of medicine after he came to Toledo in 2013 to hear author Wendy Moore speak about her biography of the 18th century Scottish physician Dr. John Hunter.

Raza’s sister has also presented the Hussain lecture. Dr. Azra Raza, a well-known oncologist and cancer researcher, and Chan Soon-Shiong Professor of Medicine at the Columbia University Medical Center, visited Toledo in 2017.

Azra Raza will join Tasnim Raza in Toledo to kick off a book tour for her forthcoming title “The First Cell: And the Human Costs of Pursuing Cancer to the Last.”


Toxic algae may be more dangerous for people with pre-existing conditions

Toxins produced during harmful algal blooms may be more harmful to people than previously known.

Researchers at The University of Toledo College of Medicine and Life Sciences sought out to examine how microcystin might affect individuals with non-alcoholic fatty liver disease, a widespread condition that is frequently asymptomatic. They found the toxin can significantly amplify the disease at levels below what would harm a healthy liver.

The study, published last month in the journal Toxins, follows earlier research from UToledo that found clear evidence that microcystin exposure worsens the severity of pre-existing colitis. Microcystin is a by-product of the cyanobacteria found in what is commonly known as blue-green algae.

“The take home message from our research is there are certain groups of people who need to pay extra attention and may be more susceptible to microcystin toxins. We may need to explore special preventative guidelines for those people in terms of how much microcystin they are exposed to through drinking water or other means,” said Dr. David Kennedy, an assistant professor of medicine at UToledo and one of the study’s lead authors.

Aided by nutrient runoff and warming waters, seasonal blooms of blue-green algae are flourishing across much of the United States. Not all algal blooms produce toxins, but many do.

Dr. David Kennedy, left, and Dr. Steven Haller examined how microcystin may be more dangerous for those with pre-existing conditions.

Potentially dangerous concentrations of microcystin have been found this year in ponds in New York City’s Central Park, along the Mississippi Gulf Coast, reservoirs in California, and a portion of Lake Erie’s coastline near Toledo.

While no human deaths have been linked to microcystin in the United States, deaths have been reported elsewhere — most notably among a group of kidney dialysis patients in Brazil. There also have been reports this year of pet dogs dying after exposure to blue-green algae in Texas, North Carolina and Georgia.

With annual blooms becoming more frequent and intense, researchers in the UToledo College of Medicine and Life Sciences wanted to better understand how the toxins might affect people already suffering from conditions that affect organ systems microcystin is known to attack, such as the liver.

“It’s a gray area in terms of what microcystin is really doing to you if you have a pre-existing disease state. Are you more susceptible? Are we going to have to go back and re-evaluate what we consider safe in a person with a pre-existing disease state? It’s important we start providing answers to these questions,” said Dr. Steven Haller, UToledo assistant professor of medicine.

In the liver study, researchers examined how chronic, low-level exposure of microcystin affected mice with non-alcoholic fatty liver disease compared to mice with healthy livers.

At microcystin ingestion levels below the No Observed Adverse Effect Level for healthy mice, analysis showed significant exacerbation of liver damage in mice with fatty liver disease. Researchers observed no liver damage in mice who started the experiment with healthy livers.

“Current exposure limits from the World Health Organization and the U.S. Environmental Protection Agency for humans are based off studies done in healthy animals,” Haller said. “The results of this study suggest there may be a need to review those guidelines for people with pre-existing conditions.”

They also noted major differences in how microcystin was processed by the kidneys in the two test groups.

In mice with non-alcoholic fatty liver disease, elevated levels of microcystin were found in the blood plasma, but were not detectable in the plasma of healthy mice. Mice with non-alcoholic fatty liver disease also excreted far less microcystin in their urine.

The differences seen in how microcystin was processed between the two test groups suggests that kidney function may play an important role in the increased susceptibility of the mice with pre-existing liver disease.

“This may be highly relevant to help us understand the deaths that occurred in kidney dialysis patients, and point to the need to pay particular attention to at-risk patient populations as we design preventative, diagnostic and therapeutic strategies,” Kennedy said.

The results from the liver study build on prior work from Kennedy and Haller looking at how microcystin exposure might affect individuals with inflammatory bowel disease, another common condition that impacts an estimated 1 million Americans.

In that study, published in June, the researchers demonstrated that exposure to MC-LR prolongs and worsens the severity of pre-existing colitis, contributing to significant weight loss, bleeding, and higher numbers of signaling molecules that cause inflammation.

“Based on this data we’re coming up with insights into how we can potentially treat exposures if they do occur,” Kennedy said. “This is giving us a number of insights into how we might help patients, especially patients who are vulnerable or susceptible if there was an exposure.”

The lead author of the paper published in August was doctoral student Apurva Lad. Doctoral student Robin Su was the author on the paper about inflammatory bowel disease published in June.