Diet-dependent changes in the gut microbiome of rats are associated with corresponding structural changes in their brains, according to a new study by researchers at the University of Wisconsin School of Medicine and Public Health.

Published online today in the journal Translational Psychiatry, the study is the first to use advanced MRI technology called diffusion tensor imaging (DTI) to show a direct link between dietary manipulation, gut microbiome populations, and brain structure in animal models.

Disruptions in the number, composition and taxonomic diversity of the gut microbiome have long been implicated in the development and exacerbation of some neuropsychiatric disorders in humans, including anxiety, attention deficit hyperactivity disorder, depression and schizophrenia. But while these strong associations are well recognized, it has been unknown until now whether diet-dependent changes in brain function and behavior were also accompanied by corresponding changes in neural tissue microstructure.

John-Paul Yu, MD, PhD, an assistant professor of radiology, psychiatry, and biomedical engineering and the study’s principal investigator, says his research provides a framework for better understanding how altered gut microbiome populations can exert far-reaching changes in human behavior and how advanced imaging techniques can reveal important connections between altered and maladapted gut microbiome populations and changes in brain structure.

If the study bears out in humans, Yu says it could help hasten the discovery of neuroimaging biomarkers for mental illness, which so far have eluded neuroscientists, possibly as a result of the unaccounted contributions of the gut microbiome on brain structure.

“Our method for uncovering these potential links between gut microbiome populations and changes in brain structure will guide important new studies that will further inform our understanding of neuropsychiatric disorders and possibly refine our selection of 'friendly' bacteria that could one day be used in therapies that lessen or ameliorate the burden of those diseases,” Yu says.

To test the influence of diet on neural tissue microstructure and organization, Yu and his team randomized post-weaned male rats to one of four purified and irradiated diets:

  • A standard/control diet
  • A high fat diet
  • A high fiber diet
  • A high protein, low carbohydrate diet

After the rats spent three weeks on their assigned diets, researchers performed ex-vivo whole brain diffusion tensor imaging (DTI), an MRI-based neuroimaging technique that allows researchers to estimate the location and orientation of the brain's white matter tracts. DTI analysis not only revealed global changes in white matter structural integrity based on the different diets, but also identified — after further analysis with machine learning classifiers — that there were unique populations of specific gut bacteria that predicted those structural changes.

Yu also says the study will likely complement future research designed to better understand how, if at all, these structural changes can be shaped by the consumption of prebiotics, probiotics and other means of dietary supplementation.

Other researchers include:

  • Irene Ong, PhD, and Sean McIlwain, PhD, who both hold dual appointments in the Department of Biostatistics and Medical Informatics and the UW Carbone Cancer Center
  • Jose Gonzalez, Department of Medical Physics
  • Emily Sawin, PhD, Department of Radiology
  • Andrew Schoen, Department of Computer Sciences
  • Nagesh Adluru, PhD, Waisman Laboratory for Brain Imaging and Behavior
  • Andrew Alexander, PhD, Department of Medical Physics and Department of Psychiatry