Journal Article

Gut microbiota from persons with attention-deficit/hyperactivity disorder affects the brain in mice

Dederen, Pieter J., Wiesmann, Maximilian, Verweij, Vivienne, Kozicz, Tamas, Dam, Sarita A., van Bodegom, Miranda, Franke, Barbara, Kiliaan, Amanda J., Tengeler, Anouk C., Belzer, Clara, Arias Vasquez, Alejandro, Naaijen, Jilly

2020

Overview

Background The impact of the gut microbiota on host physiology and behavior has been relatively well established. Whether changes in microbial composition affect brain structure and function is largely elusive, however. This is important as altered brain structure and function have been implicated in various neurodevelopmental disorders, like attention-deficit/hyperactivity disorder (ADHD). We hypothesized that gut microbiota of persons with and without ADHD, when transplanted into mice, would differentially modify brain function and/or structure. We investigated this by colonizing young, male, germ-free C57BL/6JOlaHsd mice with microbiota from individuals with and without ADHD. We generated and analyzed microbiome data, assessed brain structure and function by magnetic resonance imaging ( MRI ), and studied mouse behavior in a behavioral test battery. Results Principal coordinate analysis showed a clear separation of fecal microbiota of mice colonized with ADHD and control microbiota. With diffusion tensor imaging, we observed a decreased structural integrity of both white and gray matter regions (i.e., internal capsule, hippocampus) in mice that were colonized with ADHD microbiota. We also found significant correlations between white matter integrity and the differentially expressed microbiota. Mice colonized with ADHD microbiota additionally showed decreased resting-state functional MRI-based connectivity between right motor and right visual cortices. These regions, as well as the hippocampus and internal capsule, have previously been reported to be altered in several neurodevelopmental disorders. Furthermore, we also show that mice colonized with ADHD microbiota were more anxious in the open-field test. Conclusions Taken together, we demonstrate that altered microbial composition could be a driver of altered brain structure and function and concomitant changes in the animals’ behavior. These findings may help to understand the mechanisms through which the gut microbiota contributes to the pathobiology of neurodevelopmental disorders. 7eJBsCA8tMGaQzNiv1LdPB Video abstract.

• Publisher: BioMed Central,Springer Nature B.V,BMC
• Subject: ADHD / Adult / Animals / Antibiotics / Anxiety / Attention Deficit Disorder with Hyperactivity - microbiology / Attention Deficit Disorder with Hyperactivity - physiopathology / Attention deficit hyperactivity disorder / Autism / Behavior / Behavior, Animal / Bioinformatics / Biomedical and Life Sciences / Biomedicine / Brain - diagnostic imaging / Brain - physiology / Cyanobacteria / Diet / DTI / Fecal Microbiota Transplantation / Fecal microflora / Functional anatomy / Functional connectivity / Functional magnetic resonance imaging / Gastrointestinal Microbiome / Germ-Free Life / Germfree / Gray and white matter integrity / Gut microbiota / Hippocampus / Host Microbial Interactions / Humans / Hyperactivity / Intestinal microflora / Magnetic Resonance Imaging / Male / Medical Microbiology / Mental disorders / Mice / Mice, Inbred C57BL / Microbial Ecology / Microbial Genetics and Genomics / Microbiology / Microbiomes / Microbiota / Neural networks / Neurodevelopmental disorders / Neurodevelopmental Disorders - microbiology / Neurogenesis / Neuroimaging / Open-field behavior / Sensorimotor integration / Structure-function relationships / Substantia alba / Substantia grisea / Virology / Young Adult