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Gut microbiota changes in infancy herald childhood ADHD diagnosis

By Eleanor McDermid, medwireNews Reporter

Children diagnosed with attention deficit/hyperactivity disorder (ADHD) before puberty have evidence of changes in their gut microbiota before the age of 1 year, research shows.

“Observational study data, such as ours, may be critical to identify potential targets for intervention”, write Andrea Cassidy-Bushrow (Henry Ford Hospital, Detroit, Michigan, USA) and colleagues in Pediatric Research.

The study included 314 children from the Wayne County Health, Environment, Allergy and Asthma Longitudinal Study (WHEALS), 18.8% of whom had a diagnosis of ADHD by the age of 10 years (children with other neurodevelopmental disorders were excluded from the study).

The mothers of children with ADHD were significantly younger than those of neurotypical children, had a larger BMI, and had more frequently used antifungal agents prenatally (37.5 vs 17.1%) and been exposed to environmental tobacco smoke (33.9 vs 20.8%). Among the children themselves, those with ADHD were more frequently male than those who were neurotypical (74.6 vs 49.4%).

The children had stool samples collected at 1 and 6 months of age. This revealed significant differences in specific operational taxonomic units (OTUs) between the samples, at both 1 and 6 months, from children who did and did not develop ADHD.

At the age of 1 month, children with ADHD had 18 bacterial OTUs that differed significantly from those in neurotypical children – six were less abundant and 12 more – as well as three fungal OTUs, all less abundant.

At age 6 months there were 51 significantly different bacterial OTUs and three fungal OTUs. The researchers note that 14 of the differing bacterial OTUs were from the Lactobacillales order (ie, lactic acid bacteria), with all but one of these being significantly less abundant in children who subsequently developed ADHD than in the neurotypical children.

The fungal changes in the ADHD group included reduced abundance of some Candida, which the team says is “unexpected, given that Candida overgrowth, particularly C. albicans, is associated with other neurodevelopmental disorders, including autism spectrum disorder.”

Analysis of microbiota alpha diversity (diversity within a sample) revealed that Faith’s measure of phylogenetic bacterial diversity at 6 months was significantly different between the groups, with samples from children who went on to develop ADHD having significantly greater diversity after accounting for factors including child sex and various maternal variables.

However, Shannon’s measure of diversity was not significantly different between the groups, and neither were measures of bacterial richness or evenness. No measures of fungal diversity were significantly associated with ADHD in the adjusted analysis.

Bacterial beta diversity (similarity or dissimilarity between samples) at the age of 6 months was also associated with later ADHD, albeit only the unweighted UniFrac remained statistically significant after accounting for confounders.

“It is possible, although not part of the current analysis, that the association we found between higher bacterial diversity at 6 months of age and ADHD in the current study may actually reflect that children with ADHD experienced precocious gut maturation”, Cassidy-Bushrow and colleagues speculate.

They conclude: “In our study, the association of the gut bacterial microbiota with ADHD was more consistent at 6 months of age than 1 month of age, suggesting that exposures in later infancy (e.g., complementary food introduction) may influence or enhance the risk of disease.

“Further study of the gut microbiota over more frequent time points in early life will be needed to identify specific critical windows of development.”

News stories are provided by medwireNews, which is an independent medical news service provided by Springer Healthcare Ltd. © 2022 Springer Healthcare Ltd, part of the Springer Nature Group

Pediatr Res 2022; doi:10.1038/s41390-022-02051-6