Children and adolescents with attention deficit hyperactivity disorder and autism spectrum disorder share distinct microbiota compositions

ABSTRACT

An association has been suggested between altered gut microbiota, and attention deficit hyperactivity disorder (ADHD), and autism spectrum disorder (ASD), respectively. Thus, we analyzed the gut microbiota composition in children and adolescents with or without these disorders and evaluated the systemic effects of these bacteria. We recruited study participants diagnosed with ADHD, ASD, and comorbid ADHD/ASD, while the control groups consisted both of siblings and non-related children. The gut microbiota was analyzed by 16S rRNA gene sequencing of the V4 region, while the concentration of lipopolysaccharide-binding protein (LBP), cytokines, and other signaling molecules were measured in plasma. Importantly the gut microbiota compositions of cases with ADHD and ASD were highly similar for both alpha- and beta-diversity while differing from that of non-related controls. Furthermore, a subset of ADHD and ASD cases had an increased LBP concentration compared to non-affected children, which was positively correlated with interleukin (IL)-8, 12, and 13. These observations indicate disruption of the intestinal barrier and immune dysregulation among the subset of children with ADHD or ASD.

KEYWORDS:

• Autism spectrum disorder
• attention deficit hyperactivity disorder
• neurodevelopmental disorders
• microbiota
• microbiome
• gut-brain axis
• inflammation

Acknowledgments

The authors would like to thank laboratory technicians Ann-Maria Jensen, Bente Markstrøm Jensen, and Signe Agerlin Klitgaard Poulsen for excellent technical assistance, as well as medical secretary Heidi Hattmann Hjortshøj for assistance with the collection and interpretation of medical histories of participants. Furthermore, we would like to thank the clinical and research staff at the Clinic for Child and Adolescent Psychiatry and the Research Unit for Child and Adolescent Psychiatry, Aalborg University, for assistance with the recruitment of study participants as well as discussions. Finally, we would like to thank Carlos Gonzales, Justin Shaffer, and Cameron Martino from the University of California San Diego for their advice on multi-omics analyses.

Disclosure statement

No potential conflict of interest was reported by the authors.

Author contribution

CBN, MBL, PL, SH, MN, and SS designed the study. CBN recruited participants, with supervision from MBL. CBN performed sample collection and ELISA experiments. PH and MHL performed calprotectin and Meso Scale analyses, respectively. CBN performed data analysis, with assistance from JKK, MHL, MN, LR, ABV, and SS. All authors assisted in the interpretation of data. MBL, SH, MN, and SS supervised CBN. CBN drafted the manuscript, while CBN, MBL, PL, SH, MN, and SS finalized the manuscript. All authors read and approved the final manuscript.

Data availability statement

The 16S rRNA sequencing data that support the findings of this study, are freely available in NCBI SRA at https://www.ncbi.nlm.nih.gov/bioproject/?term=PRJNA701402, Bioproject ID PRJNA701402.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/19490976.2023.2211923.

Additional information

Funding

Funding was obtained from “Marie Pedersen og Jensine Heibergs Legat”, “Sofiefonden”, Niels Jensens Forskningslegat”, “EliteForsk Rejsestipendium”, and “Fru C. Hermansens Mindelegat”. The funding organizations were neither involved in protocol formulation nor in data analysis.