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

Abstract

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.

Investigating the Gut Microbiota Composition of Individuals with Attention-Deficit/Hyperactivity Disorder and Association with Symptoms

“…This suggests that, even in the absence of significant correlations with other bacteria ( Figure S7), there could be a bacterial community interaction pattern that explains more variance than a genus alone on inattention symptoms. Lastly, our lab recently performed a separate study, in which six randomly selected samples from the NeuroIMAGE cohort (same cohort studied here) were used in an animal study of human fecal microbiota transplantation into germ-free wild-type mice [51]. Mice colonized with ADHD gut microbiota had increased anxiety-like behavior and showed significantly altered structural and functional brain characteristics.…”

Multivariate associative patterns between the gut microbiota and large-scale brain network connectivity

“…Our finding of a positive correlation of Prevotella with DMN and ECN functioning and also fronto-parietal attention network modulations support these results. Previous work showed a link between gut microbiota and restingstate functional connectivity, as assessed here (9,49). Interestingly, in one study assessing bivariate relationships, Prevotella and Bacteroides were associated with insular connectivity (8).…”

GC-TOF-MS-Based Metabolomic Analysis and Evaluation of the Effects of HX106, a Nutraceutical, on ADHD-Like Symptoms in Prenatal Alcohol Exposed Mice

“…Recently, there are some efforts to control neurological disorders by applying the gut-brain axis theory, a bidirectional communication between the brain and gastrointestinal tract [ 50 , 51 ]. In cases of ADHD, there is evidence demonstrating that gut microbiota affects brain neurodevelopment [ 52 , 53 , 54 , 55 ]. For instance, Szopinska-Tokov et al suggested that inattentive behavior that appeared in ADHD patients is associated with a specific bacterium [ 53 ].…”

“…For instance, Szopinska-Tokov et al suggested that inattentive behavior that appeared in ADHD patients is associated with a specific bacterium [ 53 ]. Also, it is reported that colonizing microbiota from ADHD patients to experimental mice affects the alteration of brain structures and causes concomitant changes in the behavior [ 55 ]. In this study, we investigated intestinal perturbation in a PAE-induced ADHD-like mouse model and the regulatory effects of HX106 on the gut microenvironment by analyzing metabolite changes in colon and fecal samples.…”