Newswise — CLEVELAND  -- Researchers from Case Western Reserve University, University Hospitals Cleveland Medical Center (UH), BIOHM Health LLC, and the Louis Stokes Cleveland VA Medical Center have published a paper in the Frontiers of Nutrition, proposing a hypothesis and theory about a microbiome-driven approach to combating depression during the COVID-19 pandemic.

In their paper, Mahmoud A. Ghannoum, PhD, FAAM, FIDSA, and colleagues, write that significant stressors brought about and exacerbated by COVID-19 are associated with startling surges in mental health illnesses, specifically those related to depressive disorders.

Within a one-month period at the beginning of the COVID-19 pandemic, the researchers write that there was a reported 34.1 percent increase in prescriptions for anti-anxiety medications, an 18.6 percent increase in antidepressant prescriptions, and a 14.8 percent increase in common anti-insomnia drugs including prescribed anti-insomnia medications in the United States.

“During such a short period of time, this steep rise hints at the magnitude of COVID-19's immediate and widespread effect on mental health,” said Dr. Ghannoum, director of the Center for Medical Mycology at UH and professor of dermatology and pathology at the Case Western Reserve University School of Medicine.

In their paper, published Aug. 24, Dr. Ghannoum and colleagues examined the current literature surrounding the microbiome and gut-brain axis to advance a potential complementary approach to address depression and depressive disorders that have increased during the COVID-19 pandemic.

“The impact of the human gut microbiome on emotional health is a newly emerging field,” said Dr. Ghannoum. “While more research needs to be conducted, the current evidence is extremely promising and suggests at least part of the answer to understanding depression in more depth may lie within the microbiome.”

The microbiome is defined as the collective genomes of the microbes (composed of bacteria, fungi, protozoa and viruses) that live inside and on the human body, but primarily in the human gut. Scientists are learning that these microbes play a significant role in health and disease.

Studies also suggest the microbiome impacts our brain and emotions. The gut microbiome and the brain communicate with each other through neural, inflammatory, and hormonal signaling pathways. As a result of the two-way interaction between the gut microbiome and the brain, each can send messages that impact the other.

Dr. Ghannoum and colleagues propose that a microbiome-based holistic approach, which involves carefully annotating the microbiome and potential modification through diet, probiotics, and lifestyle changes, may address depression.

“Despite the toll that depression has on both individuals and society, understanding and effectively treating depressive disorders is difficult,” Dr. Ghannoum said. “Current research addressing the diagnosis and treatment of depression and mood disorders is ongoing, but needs more time to develop the complexities involved how to treat them.”

He said some studies have shed light on the potential correlation between COVID infection and microbiome disturbance, but have limitations that require further investigations with larger sample sizes to approximate the general population.

However, the researchers found more evidence supporting the gut-brain link and the relationship between depression and the gut microbiome. They see this connection as a potential new and more effective target for depression management.

“It is clear that the gut microbiome's makeup in individuals with depressive disorders is disrupted and lacks the appropriate levels of beneficial microorganisms,” said Dr. Ghannoum. “We believe that encouraging the growth of such beneficial microorganisms and rebalancing the gut microbiome in individuals may be a promising step toward helping individuals ease their depression via the gut-brain axis.”

The researchers propose a multifaceted approach to manage depression that involves rebalancing and maintaining the gut microbiome through diet, probiotics, and specific lifestyle changes.

  • Specifically, they call for – A healthy diet of fruits and vegetables. These nutritional factors appear to be associated with decreased depression rates, possibly due to their anti-inflammatory, neuroprotective, and prebiotic properties,” said Dr. Ghannoum. 
  • Probiotics to serve the critical function of rebalancing the microbiome and treating depression. 
  • Lifestyle habits, including exercise, sleep and stress reduction.

They write, “Not only should probiotic consumption restore the gut balance, it may also decrease the likelihood of colonization of the gut by opportunistic pathogens, as reported in many studies that analyzed the gut microbiome in COVID-19 infected patients.”

Other authors on the paper, titled “A Microbiome-Driven Approach to Combating Depression During the COVID-19 Pandemic,” are: Mary Kate Ford, of BIOHM Health LLC; Robert A. Bonomo, MD, professor of medicine at CWRU School of Medicine and with the Louis Stokes Cleveland VA Medical Center; Ahmed Gamal, MD, research fellow, and Thomas S. McCormick, PhD, assistant professor of dermatology at CWRU School of Medicine and in the Integrated Microbiome Core, Department of Dermatology, CWRU. This work was supported in part by a National Institutes of Health Grant # R01AI145289- 01A1 to Dr. Ghannoum. He is also co-founder of BIOHM Health LLC and author of the Total Gut Balance Book.



About Case Western Reserve University

Case Western Reserve University is one of the country's leading private research institutions. Located in Cleveland, we offer a unique combination of forward-thinking educational opportunities in an inspiring cultural setting. Our leading-edge faculty engage in teaching and research in a collaborative, hands-on environment. Our nationally recognized programs include arts and sciences, dental medicine, engineering, law, management, medicine, nursing and social work. About 5,100 undergraduate and 6,700 graduate students comprise our student body. Visit to see how Case Western Reserve thinks beyond the possible.

About Louis Stokes Cleveland VA Medical Center

The Cleveland VA Medical Center is the hub of VA Northeast Ohio Healthcare System, providing and coordinating primary, acute and specialty care. Focusing on treating the whole Veteran through health promotion and disease prevention, VA Northeast Ohio Healthcare System delivers comprehensive, seamless health care and social services for more than 111,538 Veterans at 18 locations across Northeast Ohio. VA Northeast Ohio Healthcare System contributes to the future of medicine through education, training and research programs. For more information visit

About University Hospitals / Cleveland, Ohio Founded in 1866, University Hospitals serves the needs of patients through an integrated network of 23 hospitals (including 5 joint ventures), more than 50 health centers and outpatient facilities, and over 200 physician offices in 16 counties throughout northern Ohio. The system’s flagship quaternary care, academic medical center, University Hospitals Cleveland Medical Center, is affiliated with Case Western Reserve University School of Medicine, Oxford University and the Technion Israel Institute of Technology. The main campus also includes the UH Rainbow Babies & Children's Hospital, ranked among the top children’s hospitals in the nation; UH MacDonald Women's Hospital, Ohio's only hospital for women; and UH Seidman Cancer Center, part of the NCI-designated Case Comprehensive Cancer Center. UH is home to some of the most prestigious clinical and research programs in the nation, with more than 3,000 active clinical trials and research studies underway. UH Cleveland Medical Center is perennially among the highest performers in national ranking surveys, including “America’s Best Hospitals” from U.S. News & World Report. UH is also home to 19 Clinical Care Delivery and Research Institutes. UH is one of the largest employers in Northeast Ohio with more than 30,000 employees. Follow UH on LinkedIn, Facebook and Twitter. For more information, visit

About BIOHM Health

BIOHM Health was founded by Dr. Ghannoum, the scientist who named the mycobiome, and one of the world's leading experts in medically important fungus and microbiome sequencing. Dr. Ghannoum's scientific research has resulted in over 400 peer reviewed scientific papers and his publications have been cited over 38,000 times.  After making the breakthrough discovery that bad bacteria and bad fungus work together to create digestive imbalance, Dr. Ghannoum realized that today's probiotics and microbiome tests had not been engineered to specifically address the role fungus plays in digestive health. As a result, he created BIOHM: The first company that addresses the gut's total microbiome of both bacteria and fungus.

Journal Link: Frontiers of Nutrition