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

The effect of psychostimulant medication in ADHD on the gut microbiome remains unknown. Oral Synbiotic 2000, comprising multiple lactic acid bacteria and dietary fibers, reduces psychiatric symptoms and plasma immune markers in ADHD, but its impact on the gut microbiome is unexplored. This study aimed to (i) study the fecal bacterial microbiome, focusing on species and bacterial gene modules, in ADHD patients and neurotypical controls, and (ii) examine microbiome changes attributable to Synbiotic 2000. Fecal samples were collected from 147 participants at baseline, and 106 completers at follow-up from a randomized placebo-controlled trial of Synbiotic 2000 conducted in children and adults with ADHD. At baseline, adult samples were compared to those of 52 adult controls, and patients on psychostimulants were compared to those not on psychostimulants in adults and children separately. The fecal microbiome was sequenced using shallow shotgun sequencing and analyzed for diversity and differential abundance using machine learning. Plasma short-chain fatty acids (SCFAs) and serum vitamin B12 levels were measured. At baseline, adult ADHD patients had significantly different abundances of four species compared to controls. In children, those on psychostimulants exhibited a higher abundance of species from the genus Prevotella, alongside a lower abundance of the vitamin B12-synthesis module, M00122, than those not on such medication. The lower M00122 abundance was associated with a looser stool consistency, implicating a shorter colonic transit time. Synbiotic 2000 did not affect taxonomic or functional α-diversity in adults or children. However, looser baseline stool consistency was linked to greater increases in evenness in the Synbiotic group over time. There was a significant Synbiotic-specific effect on taxonomic and functional β-diversity, not only the increased abundance of the Synbiotic 2000 species. Plasma levels of formic acid and propionic acid increased towards control levels in the Synbiotic group. In conclusion, distinct species were differently abundant in adults with ADHD compared to controls. The implications of the lower abundance of the vitamin B12-synthesis module, in children on psychostimulant medication, for the gut ecosystem and host intestine remain to be elucidated. Synbiotic 2000 influenced the taxonomy and functionality of the fecal microbiome and increased plasma SCFA levels towards normal. Further research is warranted to explore the clinical implications of microbiome modulation in the treatment of ADHD.