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.

A USF Health preclinical study adds to mounting evidence about the interplay between genetics and environment in mental health

TAMPA, Fla. (June 10, 2019) – Researchers continue to dig for molecular clues to better understand how gene-environment interactions influence neuropsychiatric disease risk and resilience. An increasing number of studies point to a strong association between the FKBP5 gene and increased susceptibility to depression, anxiety, post-traumatic stress disorder and other mental health disorders.

Adding to the growing evidence, a new preclinical study by University of South Florida neuroscientists finds that anxiety-like behavior increases when early life adversity combines with high levels of FKBP5 – a protein capable of modifying hormonal stress response.  Moreover, the researchers demonstrate this genetic-early life stress interaction amplifies anxiety by selectively altering signaling of the enzyme AKT in the dorsal hippocampus, a portion of the brain primarily responsible for cognitive functions like learning and memory.

While more research is required, the study suggests that FKBP5 may be an effective target for treating anxiety and other mood disorders.

USF Health neuroscientists Laura Blair, PhD, (left) study senior author, and Marangelie Criado-Marrero, PhD, lead author.  The monitor displays a cross-sectional image of a mouse hippocampus.

The findings were published June 4 in the International Journal of Molecular Sciences.

“We know that the combination of genetic variations and environmental factors can make people either more or less susceptible to mental illness – even when they experience the same types of trauma,” said senior author Laura Blair, PhD, assistant professor of molecular medicine at the USF Health Byrd Alzheimer’s Center. Postdoctoral scholar Marangelie Criado-Marrero, PhD, was lead author of the study.

“We hypothesized that high FKBP5 and early life stress might yield neuropsychiatric symptoms through altered cellular stress response pathways in the brain.”

In a series of experiments, newborn mice overexpressing human FKBP5 in the forebrain were divided into two groups – one group was exposed to an early life stress (maternal separation), and the other was not.  Two control groups were comprised of stressed and non-stressed mice without brain overexpression of FKBP5. At two months, when the mice were young adults, an elevated-plus maze with open and closed arms was used to test anxiety-like behavior. Compared to all other groups, the mice with high FKBP5 and early life stress showed more anxiety as measured by their tendency to stay within enclosed areas of the maze rather than naturally explore all arms of the maze.

Dr. Criado-Marrero and Dr. Blair

The anxiety effect was more pronounced in the female mice than in males, an observation that aligns with sex differences noted in humans with anxiety disorders, Dr. Blair said.

The researchers also analyzed molecular changes in brains of the mice. They found that AKT signaling, specifically in the dorsal hippocampus, differed depending upon whether or not the mice with high FKBP5 had experienced maternal separation as newborns. AKT signaling – shown to be altered in Alzheimer’s disease and cancer as well as in mental health disorders — affects brain cell survival and metabolism, and the brain’s ability to adapt to new information.

“The AKT signaling pathway was inversely regulated as a result of early life stress. High FKBP5 normally decreases AKT signaling, but when early life stress was added to overexpressed FKBP5 that signaling activity increased,” Dr. Blair said. “Overall, our findings highlight the importance of stress and genes (like FKBP5) in modulating vulnerability to mood disorders and learning impairments.”

The USF Health researchers plan to next study the interaction of high FKBP5 and early life stress in older mice to determine how anxiety is affected by aging.

Slides of mouse neurons were analyzed to look for molecular changes in brain cells that correspond with changes in cognition.

The study was supported by grants from the NIH’s National Institute of Mental Health and National Institute of Neurological Disorders and Stroke.

Anxiety disorders are among the most common mental health conditions in the U.S, affecting 40 million adults, and nearly one in three of all adolescents will experience an anxiety disorder, according to the NIH.

-Photos by Allison Long, USF Health Communications and Marketing