Altered gut microbiome function in ADHD: More Prevotella, less vitamin B12 biosynthesis, and beneficial modulation by synbiotic treatment.

Adult ADHD patients had significantly different abundances of four bacterial species compared to neurotypical controls at baseline.

• Fecal samples were collected from 147 participants at baseline and 106 completers at follow-up from a randomized placebo-controlled trial.
• Adult samples were compared to those of 52 adult neurotypical controls.
• Shallow shotgun sequencing was used for fecal microbiome analysis.
• Differential abundance was analyzed using machine learning methods.

Children with ADHD on psychostimulant medication exhibited a higher abundance of species from the genus Prevotella compared to those not on psychostimulants.

• Patients on psychostimulants were compared to those not on psychostimulants in adults and children separately.
• The Prevotella enrichment was specifically observed in children, not in adults.
• Prevotella species differences were identified through shallow shotgun sequencing and machine learning-based differential abundance analysis.

Children on psychostimulant medication had a lower abundance of the vitamin B12-synthesis module (M00122) compared to those not on psychostimulants.

• The lower M00122 abundance was associated with a looser stool consistency.
• Looser stool consistency implicates a shorter colonic transit time, which may explain reduced vitamin B12 biosynthesis.
• Serum vitamin B12 levels were measured alongside fecal microbiome sequencing.
• This finding was specific to children and was not reported in adults.

Synbiotic 2000 did not affect taxonomic or functional α-diversity in adults or children.

• Synbiotic 2000 comprises multiple lactic acid bacteria and dietary fibers.
• The trial was a randomized placebo-controlled design with 147 participants at baseline and 106 completers at follow-up.
• Looser baseline stool consistency was linked to greater increases in evenness in the Synbiotic group over time.
• Alpha-diversity results were consistent across both adult and child subgroups.

Synbiotic 2000 had a significant effect on taxonomic and functional β-diversity beyond just the increased abundance of the Synbiotic 2000 species themselves.

• There was a significant Synbiotic-specific effect on both taxonomic and functional β-diversity.
• The β-diversity changes were not solely attributable to the increased abundance of the Synbiotic 2000 bacterial strains.
• This suggests broader community-level modulation of the gut microbiome by Synbiotic 2000.

Plasma levels of formic acid and propionic acid increased towards control levels in the Synbiotic 2000 treatment group.

• Plasma short-chain fatty acids (SCFAs) were measured alongside gut microbiome sequencing.
• Formic acid and propionic acid specifically increased in the Synbiotic group.
• The SCFA changes moved towards levels observed in neurotypical controls.
• Oral Synbiotic 2000 had previously been shown to reduce psychiatric symptoms and plasma immune markers in ADHD.