Virginia Tech scientists find link between microorganisms and early brain development

A new study by Virginia Tech scientists revealed a potential connection between microorganisms that live in the gut and elsewhere in the body and early brain development that may be related to disorders such as autism, schizophrenia, depression, and attention deficit hyperactivity disorder.

Researchers with the Virginia-Maryland College of Veterinary Medicine and the Fralin Biomedical Research Institute at VTC used a powerful new magnetic resonance imaging scanner to study brain development in the absence of a range of microorganisms.

“We’re interested in how other parts of the body can affect the brain,” said Paul Morton, assistant professor of neurodevelopment and neurobiology in the Virginia-Maryland College of Veterinary Medicine and the paper’s corresponding author. “What we found are indications that microbiota – bacteria, viruses, and fungi, most likely in the gut – play a critical role in brain development during early life, when it’s vulnerable to environmental factors that can result in disabilities later on.”

Published in the journal Frontiers in Cellular Neuroscience in December, the study is the first to use the Fralin Biomedical Research Institute’s Bruker BioSpec 94/20 USR scanner, part of its core research facilities. The scanner has a small diameter bore allowing for concentrating the magnetic field and accommodating small laboratory animals or isolated brains.

Magnetic resonance imaging depends on powerful magnets, and the one used in this study utilizes a 9.4 Tesla magnet, considerably more powerful than either the 1.5 or 3.0 Tesla MRIs found in hospitals and clinics. This high magnetic field strength MRI allows for much higher resolution imaging of the brain with cleaner signals and less noise in the images than less powerful magnets.

“This device allows us to provide researchers with very high-resolution and high-contrast images, to see the whole brain in incredible detail,” said Maosen Wang, one of the co-authors of the study and director of the research institute’s small-bore MRI facility.

For the study, the research team developed a germ-free swine model — which has many similarities to humans in brain development and in the gastrointestinal tract — and used MRI, cellular analyses, and biochemical methods to demonstrate the impact of microbiota on development of white matter in the brain. White matter is largely comprised of myelin, a lipid-rich sheath that helps facilitate communication between neurons.

The study focused on the period starting immediately after birth, when the brain continues growing rapidly and microbes are introduced to the body.

“What we found is that a particular white matter tract underlying an area at the front of the brain, called the prefrontal cortex, is significantly underdeveloped in germ-free animals, suggesting that the microbiota promote normal development in that region,” Morton said.

Another part of the brain, the corpus collosum, which connects the left and right parts of the brain, was also affected.

The researchers suspect that white matter has less of a chance to mature without the beneficial influence of microbiota.

Further, the study examined the influence of microbiota on the developmental progression of a type of glial cell in the brain called an oligodendrocyte. These cells produce myelin, which insulates the wiring between neural connections to speed up their communication. The researchers found fewer of these cells were produced in those regions of the brain, which diminishes the production of myelin, and could slow or disrupt communication between neurons.

The findings add to a growing body of research supporting existence of the gut-brain axis, a link between the gut and the central nervous system. The influence of microorganisms on brain development has recently been brought into the clinical and research spotlight as alterations in microbiota have been implicated in some previous studies in health conditions including autism spectrum disorders, schizophrenia, depression, and anxiety via the gut-brain axis. 

Researchers will next try to isolate the location of the microorganisms impacting these brain regions and identify which bacteria, viruses, and/or fungi are involved.

“We are also interested in determining if these impacts on brain development are permanent or if there is a timeframe in which we can intervene to promote healthy growth,” Morton said. “One advantage to this approach is that it offers minimally invasive treatment options including changes in antibiotic regimens or supplementing patients with pre-, pro-, and/or symbiotics to overcome potential mental health disorders.”

The Bruker MRI used in the study is one of several scanners that are part of the Fralin Biomedical Research Institute’s core research facilities, including four other MRI scanners for human subjects, computed tomography scanners for humans and animals, MRI-guided high-field focused ultrasound, and an array of confocal and electron microscopes.

Sadia Ahmed, graduate student in biomedical and veterinary sciences at the Virginia-Maryland College of Veterinary Medicine is the study’s first author. Other authors include Lijuan Yuan, professor of virology and immunology at the veterinary college; Brittany Howell, assistant professor at the Fralin Biomedical Research Institute; Stephen LaConte, associate professor at the Fralin Biomedical Research Institute; and Alicia Pickrell, associate professor in Virginia Tech’s School of Neuroscience.

This study was funded in part by the National Institutes of Health and startup funds from the Virginia-Maryland College of Veterinary Medicine.