Reduced microbiome alpha diversity in young patients with ADHD

Alexander Prehn‐Kristensen, Alexandra Zimmermann, Lukas Tittmann, Wolfgang Lieb, Stefan Schreiber et al. (+2)•View original
HighlightsBalancedcoral voice
Attention-deficit and hyperactivity disorder touches a lot of families — roughly three to five percent worldwide — and it's not just about fidgeting or forgetting homework. The core symptoms trace back to dopamine signaling and fronto-striatal brain circuits. However, genes and brain scans aren't the whole story. What kids eat, how their immune system functions, and the trillions of microbes in their gut all communicate with the brain through what we call the gut-brain axis. That's a real, bidirectional communication line. The obvious question is: do kids with ADHD carry a different microbial community in their gut? Prehn-Kristensen and colleagues took a straightforward, careful approach to that. They recruited a small pilot cohort — 14 boys with ADHD and 17 healthy peers, around middle-school age — and profiled the bacteria in their stool using sixteenth ribosomal DNA sequencing, the standard way to get a census of "who's there." They normalized each sample to the same sequencing depth of seven thousand reads and clustered similar sequences into operational taxonomic units so they could compare apples to apples. Then they looked at two things: diversity within each child's microbiome, and how communities differed across children. For statistics, they leaned on well-worn tools: Shannon diversity for within-sample evenness, and non-metric multidimensional scaling with Bray-Curtis distances for between-sample composition, using permutation tests to see if groups really separated. They also used Linear discriminant analysis Effect Size, or LEfSe, a biomarker method, to highlight taxa that consistently mark one group over another, and a constrained redundancy analysis to relate microbes to symptom ratings. Here's the headline on diversity within a sample. Kids with ADHD had lower Shannon diversity — that's the metric that combines how many species you have with how evenly they share the space — with a p-value of 0.036. Two measures of sheer richness, observed species and Chao one, didn't differ significantly between groups, with p-values of 0.25 and 0.17. In plain terms, it wasn't that kids with ADHD were missing lots of types of bacteria; their communities were less balanced. Between samples, the communities shifted. When mapping out the gut profiles in a low-dimensional space, the ADHD group clusters apart from controls. That separation held up statistically: ANOSIM had a p-value of 0.033, and ADONIS had a p-value of 0.006. There was also a difference in dispersion — variability within groups — with a betadisper p-value of 0.002. So it's not just a subtle reshuffling; the overall community structure changes. Which microbes are carrying that signal? LEfSe pointed to two Bacteroides operational taxonomic units — labeled OTU seven and OTU five hundred seventy-seven — as markers of ADHD. At the genus level, Neisseria flagged the ADHD group, while Prevotella and Parabacteroides leaned toward controls. Looking one step up, families like Prevotellaceae, Catabacteriaceae, and Porphyromonadaceae were higher in controls; Neisseriaceae was higher in ADHD. Broad, phylum-level shifts didn't reach significance, but there was a trend toward more Bacteroidaceae in the ADHD group. Think of it as a change in specific players rather than a wholesale turnover of the league. The microbiome also tracked behavior. Hyperactivity scores correlated with lower alpha diversity, with a correlation of minus 0.35 and a p-value of 0.03. In the constrained analysis, that Bacteroides OTU seven aligned with higher hyperactivity and impulsivity. That's not proof of cause, but it suggests a bridge between symptoms and the microbes that live with us. A quick note of humility: this was a small, male-only, cross-sectional snapshot. It can't tell us what comes first, and it doesn't address medication effects. But as a first map, it's clear: in this cohort, ADHD came with a less even gut ecosystem, a shifted community structure, and a short list of microbial markers that stand out. The next step is simple but hard — follow kids over time, control for medications and diet, and see whether these microbial signatures change with the symptoms. That's how a curious signal turns into a story we can act on.

Attention-deficit and hyperactivity disorder touches a lot of families — roughly three to five percent worldwide — and it's not just about fidgeting or forgetting homework. The core symptoms trace back to dopamine signaling and fronto-striatal brain circuits. However, genes and brain scans aren't the whole story.

What kids eat, how their immune system functions, and the trillions of microbes in their gut all communicate with the brain through what we call the gut-brain axis. That's a real, bidirectional communication line. The obvious question is: do kids with ADHD carry a different microbial community in their gut?

Prehn-Kristensen and colleagues took a straightforward, careful approach to that. They recruited a small pilot cohort — 14 boys with ADHD and 17 healthy peers, around middle-school age — and profiled the bacteria in their stool using sixteenth ribosomal DNA sequencing, the standard way to get a census of "who's there." They normalized each sample to the same sequencing depth of seven thousand reads and clustered similar sequences into operational taxonomic units so they could compare apples to apples. Then they looked at two things: diversity within each child's microbiome, and how communities differed across children.

For statistics, they leaned on well-worn tools: Shannon diversity for within-sample evenness, and non-metric multidimensional scaling with Bray-Curtis distances for between-sample composition, using permutation tests to see if groups really separated. They also used Linear discriminant analysis Effect Size, or LEfSe, a biomarker method, to highlight taxa that consistently mark one group over another, and a constrained redundancy analysis to relate microbes to symptom ratings.

Here's the headline on diversity within a sample. Kids with ADHD had lower Shannon diversity — that's the metric that combines how many species you have with how evenly they share the space — with a p-value of 0.036. Two measures of sheer richness, observed species and Chao one, didn't differ significantly between groups, with p-values of 0.25 and 0.17.

In plain terms, it wasn't that kids with ADHD were missing lots of types of bacteria; their communities were less balanced.

Between samples, the communities shifted. When mapping out the gut profiles in a low-dimensional space, the ADHD group clusters apart from controls. That separation held up statistically: ANOSIM had a p-value of 0.033, and ADONIS had a p-value of 0.006.

There was also a difference in dispersion — variability within groups — with a betadisper p-value of 0.002. So it's not just a subtle reshuffling; the overall community structure changes.

Which microbes are carrying that signal? LEfSe pointed to two Bacteroides operational taxonomic units — labeled OTU seven and OTU five hundred seventy-seven — as markers of ADHD. At the genus level, Neisseria flagged the ADHD group, while Prevotella and Parabacteroides leaned toward controls.

Looking one step up, families like Prevotellaceae, Catabacteriaceae, and Porphyromonadaceae were higher in controls; Neisseriaceae was higher in ADHD. Broad, phylum-level shifts didn't reach significance, but there was a trend toward more Bacteroidaceae in the ADHD group.

Think of it as a change in specific players rather than a wholesale turnover of the league.

The microbiome also tracked behavior. Hyperactivity scores correlated with lower alpha diversity, with a correlation of minus 0.35 and a p-value of 0.03. In the constrained analysis, that Bacteroides OTU seven aligned with higher hyperactivity and impulsivity.

That's not proof of cause, but it suggests a bridge between symptoms and the microbes that live with us.

A quick note of humility: this was a small, male-only, cross-sectional snapshot. It can't tell us what comes first, and it doesn't address medication effects. But as a first map, it's clear: in this cohort, ADHD came with a less even gut ecosystem, a shifted community structure, and a short list of microbial markers that stand out.

The next step is simple but hard — follow kids over time, control for medications and diet, and see whether these microbial signatures change with the symptoms. That's how a curious signal turns into a story we can act on.