Altered Gut-Microbiota Correlates with Clinical Symptoms and Fiber Tract Integrity in ADHD Children
Poster No:
280
Submission Type:
Abstract Submission
Authors:
Haiti Lin1,2, Jung-Chi Chang1,2, Susan Shur-Fen Gau1,2
Institutions:
1National Taiwan University Hospital and College of Medicine, Department of Psychiatry, Taipei, Taiwan, 2Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan
First Author:
Haiti Lin
National Taiwan University Hospital and College of Medicine, Department of Psychiatry|Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University
Taipei, Taiwan|Taipei, Taiwan
National Taiwan University Hospital and College of Medicine, Department of Psychiatry|Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University
Taipei, Taiwan|Taipei, Taiwan
Co-Author(s):
Jung-Chi Chang
National Taiwan University Hospital and College of Medicine, Department of Psychiatry|Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University
Taipei, Taiwan|Taipei, Taiwan
National Taiwan University Hospital and College of Medicine, Department of Psychiatry|Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University
Taipei, Taiwan|Taipei, Taiwan
Susan Shur-Fen Gau
National Taiwan University Hospital and College of Medicine, Department of Psychiatry|Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University
Taipei, Taiwan|Taipei, Taiwan
National Taiwan University Hospital and College of Medicine, Department of Psychiatry|Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University
Taipei, Taiwan|Taipei, Taiwan
Introduction:
Recent studies suggest altered gut microbiota in attention-deficit/hyperactivity disorder (ADHD), and indicate potential links between gut microbiota and clinical symptoms (Caputi et al., 2024). Diffusion imaging studies have revealed decreased fiber tract integrity in individuals with ADHD, particularly in brain regions related to interhemispheric connectivity, visual processing, and reward pathways (Kabukcu Basay et al., 2016). However, the influence of gut microbiota composition on brain structure remains unclear. This study investigates the relationships among gut microbiota, brain structural integrity, and ADHD symptoms in drug-naïve children with ADHD compared to typically developing children (TDC).
Methods:
The study included 68 drug-naive children with ADHD and 60 TDC, aged 4–12 years. All the participants received clinical, intelligence, and MRI assessments and provided stool samples. Gut microbiota were analyzed using full-length 16S rRNA sequencing, while DTI data were analyzed using correlational tractography in DSI Studio. Clinical assessments included the SNAP-IV, the Behavior Rating Inventory of Executive Function, and a gastrointestinal symptoms questionnaire. A Spearman partial correlation model was employed to examine associations between significant gut microbiota-identified through differential abundance analysis-and clinical symptoms, along with specific DTI metrics, controlling for age, sex, full-scale IQ (FIQ), and body mass index (BMI) were included as covariates. The false discovery rate (FDR) was applied by using the Benjamini-Hochberg procedure.
Results:
No significant differences were noted between the ADHD and TDC groups in terms of sex, age, FIQ, or BMI profiles (Table 1). Children with ADHD exhibited more severe upper gastrointestinal symptoms, altered bowel habits, and distinct food preferences. Differential abundance analysis using LefSe analysis (LDA > 4) showed that the ADHD group had a higher abundance of the family Bacteroidaceae and a lower abundance of the family Lachnospiraceae. Additionally, the Wilcoxon rank-sum test identified that the Cutibacterium acnes was more abundant in ADHD. Functional pathway analysis using PICRUSt2 showed that four pathways were more prominent in ADHD: chorismate biosynthesis, UDP-sugar biosynthesis, lipid anchor biosynthesis, and L-valine degradation. Correlational tractography revealed that children with ADHD exhibited lower fractional anisotropy values in the left inferior longitudinal fasciculus, bilateral cerebella, and corpus callosum. Reduced axial diffusivity and mean diffusivity across multiple brain regions were also observed in the ADHD group. The relative abundance of the genus Cutibacterium was positively associated with inattention (ρ = 0.25, p = 0.008, FDR = 0.02) and daily life executive dysfunction (ρ = 0.27, p = 0.005, FDR = 0.02). Furthermore, the relative abundance of Cutibacterium was negatively associated with the mean diffusivity of the right cerebellum (ρ = -0.27, p = 0.029).
Conclusions:
This study identified significant gut-brain-behavioral relationships in ADHD, highlighting the role of gut microbiota in neurocognitive and structural alterations associated with the disorder. Specifically, the abundance of the ADHD-specific genus Cutibacterium was positively correlated with inattention and executive dysfunction and negatively correlated with the mean diffusivity of the right cerebellum. Furthermore, the chorismate biosynthesis pathway was significantly elevated in ADHD, with Cutibacterium acnes identified as a producer of chorismate synthase. Chorismate, a precursor in the metabolic pathways of tryptophan and tyrosine, is critical for synthesizing dopamine and serotonin, key neurotransmitters implicated in ADHD-related neurocognitive deficits. These findings provide novel insights into the gut-brain axis and its role in the pathophysiology of ADHD, offering a basis for future research into microbiome-based therapeutic strategies and underlying mechanisms.
Disorders of the Nervous System:
Neurodevelopmental/ Early Life (eg. ADHD, autism) 1
Modeling and Analysis Methods:
Diffusion MRI Modeling and Analysis 2
Keywords:
Attention Deficit Disorder
Tractography
WHITE MATTER IMAGING - DTI, HARDI, DSI, ETC
1|2Indicates the priority used for review
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Kabukcu Basay, B., Buber, A., Basay, O., Alacam, H., Ozturk, O., Suren, S., Ay, O. L., Acikel, C., Agladıoglu, K., Erdal, M. E., Ercan, E. S., Herken, H. (2016). White matter alterations related to attention-deficit hyperactivity disorder and COMT val(158)met polymorphism: children with valine homozygote attention-deficit hyperactivity disorder have altered white matter connectivity in the right cingulum (cingulate gyrus). Neuropsychiatr Dis Treat, 12, 969-981. doi:10.2147/ndt.S104450