The new research may help identify measures to prevent or delay mild cognitive impairment and dementia

Can what you eat influence the health of your brain now and in the future?

That is a key question that USF Health Morsani College of Medicine researchers hope to answer with the help of a noninvasive Microbiome in the Aging Gut and Brain (MiaGB) study.

The new clinical study expects to enroll 400 adults ages 60 and older in the Tampa Bay region and beyond — both those who are cognitively healthy as well as those diagnosed with mild cognitive impairment and early-stage dementia.

The researchers will analyze the composition of bacteria in stool samples and saliva samples (oral swabs) donated by study participants one time at the beginning of the study and then once a year for at least five years. They will track alterations over time in the populations of oral and gut microorganisms, collectively known as the microbiome. Using an interactive mobile app, study participants will complete a daily dietary recall questionnaire and yearly tests of their memory, speed of thinking, and other cognitive abilities.

“We want to know, based on changes in the microbiome ‘signature’ from the saliva and stool samples, if we can predict an older person’s risk of developing cognitive decline or dementia. And can we do that early enough to delay or prevent those age-related diseases – either by modifying the individual’s diet or the microbiome itself,” said Hariom Yadav, PhD, an associate professor of neurosurgery and brain repair at the Morsani College of Medicine and director of the USF Center for Microbiome Research.

Several studies have correlated healthy guts, characterized by a well-balanced diversity of microorganisms, with healthy aging. Alzheimer’s disease and other dementias are among the growing number of medical conditions linked to an imbalance of microorganisms (more bad bugs than good bugs) within the intestines. Emerging evidence also suggests that oral health and brain health are interconnected, including a large National Institute on Aging study last year linking gum disease with dementia.

Hariom Yadav, PhD, (standing) and Shalini Jain, PhD, are faculty members at the USF Center for Microbiome Research, based in the USF Health Morsani College of Medicine. Their research focuses on the gut-brain connection (gut-brain axis) in relation to cognitive function.  — Photo by Allison Long, USF Health Communications and Marketing

The daily food intake logged by study participants will indicate any deficiencies in their usual diets, said Shalini Jain, PhD, the MiaGB study’s IRB principal investigator and USF Health assistant professor of neurosurgery and brain repair. “We’ll be able to evaluate the effects that certain types of foods (i.e, protein, fruits, vegetables, dairy, carbohydrates, fermented foods, and junk food) have on the growth of certain types of bacteria and see how the mix of bacteria changes if the diet is modified.”

Study participants may benefit by learning more about the calories and nutritional balance (or imbalance) in their diets, Dr. Jain added. Based on the dietary information reported, the mobile app suggests healthy habits that can be incorporated into the individual’s lifestyle.

Ronald Day and his wife Ardell, both 74, were among the first to enroll in the MiaGB study after attending a presentation about the USF Health microbiome research. Day, a retired pastor and volunteer chaplain at his Tampa continuing care retirement community, said he was intrigued by the idea that populations of microorganisms in the gut may affect cognitive skills controlled by the brain.

“On a practical level, I’m hoping to learn something about my eating habits from the food diaries we keep that might indicate what foods I should add to my diet, or which to avoid,” Day said. “And in the future, I’m hoping researchers learn enough from studies like this to suggest individualized diets (or other interventions) tailored to our own microbiomes.”

As someone in “the last third of life,” Day added, he’s keenly aware of the need to prevent or delay cognitive decline. “One of our neighbors is in the early stages of Alzheimer’s disease, and it’s been difficult for the family… Anything that can help maintain mental acuity as we age is so important.”

Photo by Allison Long, USF Health Communications and Marketing

Aging is not a disease, Dr. Yadav emphasized, but as people age it’s particularly important to keep a healthy balance of intestinal microbes so that a potentially harmful strain of bacteria does not overgrow and monopolize the food source of beneficial bacteria. “A healthy gut allows you to adequately absorb the healthier nutrients and keep a check on the stimulation of inflammation, which is a root cause of several age-related conditions, including abnormal cognitive function,” he said.

For more information about the MiaGB study, please email jains10@usf.edu or call (813) 974-6281.

Seeking to understand how the heart short circuits, Sami Noujaim looks for new drugs to fix atrial fibrillation

Within the last three years, USF biomedical scientist Sami Noujaim, PhD, lost his older brother to sudden cardiac death and his 80-year-old father was diagnosed with atrial fibrillation.

The experiences gave Dr. Noujaim a new appreciation for his research on understanding how normal and abnormal electrical impulses are generated in the heart. The Cardiac Electrophysiology Research Laboratory he directs focuses on finding more effective drugs to treat atrial fibrillation, the most common irregular heart rhythm and a condition for which prevalence rises markedly after age 65.

Sami Noujaim, PhD, directs the Cardiac Electrophysiology Research Laboratory in the USF Health Department of Molecular Pharmacology and Physiology.

“When life throws something like that at you, the work you do takes on a more personal tone, a sense of mission.  I realized that neither myself nor my loved ones are immune from the cardiovascular diseases I’m studying,” said Dr. Noujaim, an assistant professor in the Morsani College of Medicine’s Department of Molecular Pharmacology and Physiology. “We are all at risk.”

 Dr. Sami Noujaim describes the focus of his laboratory’s research.

Searching for noninvasive solutions to atrial fibrillation

Atrial fibrillation is a problem with the cardiac electrical circuitry that controls the rate and rhythm of the heartbeat. The condition affects about 9 percent of the U.S. population age 65 or older, according to the Centers for Disease Control and Prevention, and can lead to potentially deadly complications such as stroke and heart failure. While signs of atrial fibrillation may include heart palpitations, fatigue, lightheadedness, dizziness and shortness of breath, some people experience no noticeable symptoms.

Treatment and management options include lifestyle changes, medications to help control heart rate and rhythm and reduce the risk of blood clots, controlled electrical shock (cardioversion to reset heart rhythm), invasive procedures (catheter ablation) and surgical implantation of pacemakers.  However, a major challenge is that atrial fibrillation frequently recurs after normal heart rhythm (sinus rhythm) is restored.

“The existing treatments can be good, but there is a lot of room for improvement, so we are focusing on contributing to noninvasive treatment options,” Dr. Noujaim said. “If we could help physicians get patients with atrial fibrillation to long-term normal sinus rhythm, and perhaps increase the ability to take them off blood thinners, it would be a significant improvement.”

Dr. Noujaim’s laboratory uses specialized equipment to measure the electrical activity of heart muscle cells and image what he describes as “atrial fibrillation in a dish.”

Closing in on a pathway linking aging and Afib

Dr. Noujaim currently works with colleagues at USF and other institutions, including Tufts University, the University of Michigan, and Northeastern University, to investigate how age-related changes in specific potassium ion channels known as GIRK may trigger a cascade of molecular events leading to atrial fibrillation. His research, supported by a five-year $2.14 million RO1 grant from the National Heart, Lung and Blood Institute employs techniques including structural biology, molecular simulations, and cellular and whole organ electrophysiology.

The researchers hypothesize that in aging-associated atrial fibrillation, the condition may arise when a biochemical pathway controlling the GIRK postassium channels begins behaving abnormally, in part because of structural and metabolic cardiovascular changes that occur with aging.  High blood pressure, diabetes, and coronary artery disease– among the most common risk factors for atrial fibrillation – become more common as people grow older.

At USF, Dr. Noujaim collaborates with Javier Cuevas, PhD, in Molecular Pharmacology and Physiology, Michael Teng, PhD, in Molecular Medicine and in Allergy and Immunology, and Juan Del Valle, PhD, in Chemistry to investigate ways to target and block the GIRK potassium channels using pharmacological approaches that rely on immunology and chemistry.

Mohammed Alhadidy (left), a biomedical graduate student, and Bojjibabu Chidipi, PhD, a postdoctoral scholar in Molecular Pharmacology and Physiology, record the electrical signals from several cells using a multichannel automated patch clamp.

 The significance of investigating the relationship between aging and atrial fibrillation.

Designing a “perfect plug” using an antimalarial drug model

“Right now, we are trying to design a perfect plug using the antimalarial drug chloroquine as a model,” Dr. Noujaim said, “We have evidence that if we block that specific type of potassium channels we will be able to stop atrial fibrillation or at least reduce its occurrence.”

Earlier work by Dr. Noujaim and others, including a study reported in the journal FASEB, demonstrated that the antimalarial drug chloroquine was effective in blocking the GIRK potassium channels and suggested a new path for discovering antiarrhythmic drugs.

Dr. Noujaim continues using cellular and animal models to pinpoint how and where the chloroquine molecule interacts with the potassium channel – with the aim of discovering a “plug” that works even better than the antimalarial drug. At the same time, he has reached out to USF Health Department of Cardiovascular Sciences to begin applying the laboratory findings to the clinic.

Working with cardiologists Bengt Herweg, MD, and Dany Sayad, MD, Dr. Noujaim recently gained approval for a pilot study to enroll 40 adults without heart damage whose atrial fibrillation has persisted more than one week and less one year. The team will test the effectiveness of chloroquine in restoring and maintaining normal heart rhythm in patients with atrial fibrillation.

The laboratory uses techniques including structural biology, molecular simulations, and cellular and whole organ electrophysiology to conduct its NIH-funded research.

Collaborating with clinicians on new treatment options

Dr. Sayad, initially surprised at Dr. Noujaim’s proposal to try chloroquine, said the strength of the preclinical data convinced him of the antimalarial drug’s potential as another antiarrhythmic option. “Treating atrial fibrillation can be especially challenging in older patients, who experience a higher recurrence of atrial fibrillation (following cardioversion) and more failure on drugs used to regulate heart rhythm,” he said.

Clinicians help biomedical scientists like Dr. Noujaim frame and focus their studies to make the research more relevant to challenges faced in treating patients, such as maintaining sinus rhythm once a normal heartbeat has been restored.

“It does not mean that the fundamental, basic science questions are not important,” Dr. Noujaim said. “To the contrary, those questions are at the heart of every single experiment we do; however, we must always think about the big picture and why we are asking those questions. And that always goes back to the clinic.”

In previous electrophysiology experiments, Dr. Noujaim and colleagues helped better define the contribution of the nervous system within the heart, otherwise known as the intrinsic cardiac ganglia, to normal and abnormal heart rhythm. Using both mouse models and patients with atrial fibrillation, the study shed light on how nerves emerging from these cardiac ganglia regulate activity of the sinus node, the heart’s natural pacemaker.  The study appeared in Cardiovascular Research in 2013.

Dr. Noujaim with members of his research team, from left, Bojjibabu Chidipi, Mohammed Alhadidy and laboratory manager Michelle Reiser.

 Dr. Noujaim comments on the importance of a clinical perspective to frame biomedical research.

Impressed by USF’s biomedical research opportunities

Dr. Noujaim came to USF in 2015 from the Molecular Cardiology Research Institute at Tufts University School of Medicine. He received his PhD in pharmacology, with distinction, from SUNY Upstate Medical University in Syracuse, NY, followed by a year of postdoctoral training there.  He then completed a three-year postdoctoral fellowship, supported by the American Heart Association, and the National Institutes of Health, at the Center for Arrhythmia Research, University of Michigan, in Ann Arbor, MI.

Dr. Noujaim said he was attracted to USF by the opportunity to be part of an emerging preeminent university committed to establishing a cardiovascular institute bridging top biomedical research and clinical care.

“The opportunities that the University of South Florida is providing for scientists are equal or greater than those at any other major academic medical center,” he said.  “It was also striking to me that, in a place the size of USF, the USF Health leadership is so actively engaged in research, with their own laboratories and grants. That’s not what you would see in a lot of places, and as a biomedical scientist it makes me feel that the leadership here really values research.”

Dr. Noujaim is passionate about the cardiovascular research his laboratory conducts, which he says has taken on a greater sense of mission since his own family’s experience with sudden cardiac death and atrial fibrillation. 

 His take on the benefit of brainstorming with scientists in other disciplines.

Some things you may not know about Dr. Noujaim:

• Born in Lebanon, he moved to the United States after graduating from high school.
• He routinely swims laps in an indoor pool.
• He enjoys experimenting with cooking, specializing in inventing new dishes by combining ingredients he finds in his refrigerator. “I’ve discovered by trial and error that no matter how bad what I cook really is, adding a tablespoon of soy sauce makes it alright,” he said.
• His first scientific experiment as a college student volunteering in Boston’s Beth Israel Deaconess Medical Center laboratory was unforgettable. He fainted while his blood was being drawn so he could use it to help study blood platelet activation and aggregation. Click on video below to find out more.

//www.youtube.com/watch?v=kGRALvR46qM

-Photos and video by Eric Younghans, and audioclips by Sandra C. Roa, USF Communications and Marketing