Table 3.

Evidence of microbiota alterations in ADHD.

Study characteristics	Microbiota assessment	Increasing microbial taxa	Decreasing microbial taxa	Microbiota and ADHD symptoms	Functional pathways
Jiang et al. (2018) Cohort (CASP Score: 15) Sample size: N = 83 Age range (years): 6-10 Dietary habits: Documented; not included in the analysis GI symptoms: Not investigated	16S rRNA sequencing (Stool samples) Alpha diversity No differences Beta diversity No differences	Family ↑Peptostreptococcaceae Moraxellaceae Xanthomonadaceae Peptococcaceae Genus No increase was observed	Family ↓Alcaligenaceae Genus ↓Faecalibacterium, Lachnoclostridium Dialister Sutterella	Negative correlation between Faecalibacterium and severity of ADHD symptoms (CPRS score and the hyperactivity index score)	Not investigated
Prehn-Kristensen et al. (2018) Cohort (CASP Score: 19) Sample size: N = 31 Age range (years): 12-14 Dietary habits: Not investigated GI symptoms: Not investigated	16S rRNA sequencing (Stool samples) Alpha diversity No difference in the observed species (Chao1 index) and richness between ADHD and NT ↓richness and evenness (Shannon index) in ADHD (w/w or w/o medications) compared to NT ↓richness and evenness (Shannon index) in the mothers of ADHD compared to NT, no changes in the fathers Beta diversity ADHD microbiota is different from NT Mothers of ADHD children have different microbiota from ADHD children and NT children	Family ↑Neisseriaceae, Bacteroidaceae Genus ↑Neisseria frequency in ADHD (No difference in Neisseria abundance in ADHD)	Family ↓Prevotellaceae, Catabacteriaceae, Porphyromonadaceae Genus No decrease was observed	Negative correlation between the levels of hyperactivity and the reduction in alpha diversity in ADHD Two species belonging to the genera Bacteroides are associated with ADHD (OTU_7, OTU_577) Positive correlation between Bacteroides and levels of hyperactivity and impulsivity in ADHD	Not investigated
Wang et al. (2020) Cohort (CASP Score: 17) Sample size: N = 60 Age range (years): 6-16 Dietary habits: Documented and include in microbiota analysis: ADHD display ↑intake of refined grains and ↓dairy and vitamin B2 intake In ADHD: -S. stercoricanis had negative correlation to the intake of dairy, and a positive correlation with nuts/seeds/legumes as well as ferritin and magnesium intake -B uniformis was positive correlated to fat and carbohydrate intake. GI symptoms: Not investigated	16S rRNA sequencing (Stool samples) Alpha diversity ↑Shannon index (richness and evenness) and Chao1 index (species abundance) ↓Simpson index (number of species and relative abundance of each species) in ADHD Beta diversity No differences	Phylum ↑Fusobacteria Genus ↑Fusobacterium Species ↑Bacteroides uniformis Bacteroides ovatus Sutterella stercoricanis	Phylum No decrease was observed Genus ↓Lactobacillus Species ↓Bacteroides coprocola	Positive correlation between B. ovatus and S. stercoricanis with ADHD clinical symptoms Possible outcomes Potential association between Bacteroides sp. and the development of the frontal lobe, cerebellum, and hippocampus	Not investigated
Wan et al. (2020) Case–control (CASP Score: 20) Sample size: N = 34 Age range (years): 6-12 Dietary habits: Documented; not included in the analysis GI symptoms: Not investigated	Metagenomic sequencing (Stool samples) Alpha diversity No differences Beta diversity No differences	Family ↑Odoribacteraceae Enterococcaceae Genus ↑Odoribacter Enterococcus Species ↑Bacteroides caccae Odoribacter splanchnicus Paraprevotella xylaniphila Veillonella parvula	Family ↓Veillonellaceae Oscillospiraceae* Genus ↓Faecalibacterium Species ↓Faecalibacterium prausnitzi Lachnospiraceae bacterium Ruminococcus gnavus	Not investigated	↑enzymatic pathways involved in dopamine turnover at the postsynaptic neuron; the genes encoding the catalytic subunit of PP1, threonine synthase, and 6-pyruvoyl-5,6,7,8-tetrahydropterin ↓gene encoding 4-hydroxy threonine-4-phosphate dehydrogenase (PICRUSt-KEGG database)
Richarte et al. (2021) Case–control (CASP Score: 13) Sample size: N = 200 Age range (years): 22-44 Dietary habits: Not investigated GI symptoms: Not investigated	16S rRNA sequencing (Stool samples) Alpha diversity No differences Beta diversity No differences	Family ↑Selenomonadaceae Veillonellaceae Genus ↑Dialister Megamonas	Family ↓Gracilibacteraceae in ASD-GI (compared to NT-GI) Genus ↓Gracilibacter Anaerotaenia	Positive correlation between Anaerotaenia and Gracilibacter in ADHD Negative correlation between Anaerotaenia and Megamonas in ADHD	Not investigated
Aarts et al. (2017) Cohort (CASP Score: 19) Sample size: N = 96 (NT are siblings and unrelated and are considered as one group) Age range (years): 18-21 Dietary habits: Not investigated GI symptoms: Not investigated	16S rRNA sequencing (Stool samples) Alpha diversity Not investigated Beta diversity Not investigated	Phylum ↑Actinobacteria Class ↑Bacteroidia Deltaproteobacteria Order ↑Bacteriodales Bifidobacteriodales Coriobacteriales Desulfovibrionales Family ↑Rikenellaceae Bacteroidaceae Bifidobacteriaceae Coriobacteriaceae Genus ↑Bifidobacterium Eggerthella Bacteroides Odoribacter Alistipes Parabacteroides Species ↑Bacteroides uniformis Bacteroides ovatus Bacteroides vulgatus B. longum B. adolescentis	Phylum No decrease was observed Class ↓Clostridia Order ↓Eubacteriales# Family ↓Oscillospiraceae* Lachnospiraceae Genus ↓Ruminococcus Acetivibrio Coprococcus Subdoligranulum Species No decrease was observed	Negative correlation between the abundance of predicted CDT and reward anticipation, a key symptom in ADHD and dopamine target	↑CDT in the bacteriome from ADHD compared to NT Positive correlation between ↑CDT and Bifidobacterium in ADHD Possible outcomes: ↑CDT- > ↑phenylalanine, an essential AA that crosses the BBB and acts as a precursor for dopamine and noradrenaline (PICRUSt-KEGG database)
Szopinska-Tokov et al. (2021) Cohort (CASP Score: 13) Sample size: N = 89 (NT are siblings and unrelated and are considered as one group) Age range (years): 13-29 Dietary habits: Not investigated GI symptoms: Not investigated	16S rRNA sequencing (Stool samples) Alpha diversity No differences Beta diversity No differences	In ADHD compared to NT Genus ↑Intestinibacter (low relative abundance in both groups) In ADHD-medicated compared to ADHD-naïve Genus No increase was observed	In ADHD compared to NT Genus ↓Coprococcus Prevotella In ADHD-medicated compared to ADHD-naïve Genus ↓Lactobacillus Lachnospiraceae_ND3007 Ruminococcaceae_ g Ruminococcaceae_UCG.014	Correlation between Coproccocus_2 with ADHD symptoms, specifically inattention symptoms (non-significant)	Not investigated

AA, amino acids; ADHD, attention deficit hyperactivity disorder; BBB, Blood Brain Barrier; CASP, Critical Appraisal Skills Program; CDT, cyclohexadienyl dehydratase; CPRS, Conner’s Parent Rating Scales; GI, gastrointestinal; KEGG, Kyoto Encyclopedia of Genes and Genomes; NT, neurotypical controls; OTUs, Operational taxonomic unit; PICRUST, Phylogenetic Investigation of Communities by Reconstruction of Unobserved States; PP1, protein phosphatase-1; rRNA, ribosomal ribonucleic acid. *Ruminococcaceae was renamed to Oscillospiraceae; #Clostridiales was amended in Eubacteriales in 2019.