Table 1.

Summary of study characteristics and findings.

Author	Question ID	Population	Health condition	Intervention	Intestinal microbiome outcomes			Mental health outcomes
					Methodologic differences to analyze gut microbiome	Summary of findings	During or post intervention outcomes	Measure(s) used to assess psychological outcomes	Psychological or neuropsychiatric outcomes	Association between gut microbiome and psychological outcomes
Partty et al. (2015)	Is the gut-brain-axis is involved in the manifestation of ADHD and AS? Is there is any association of compositional development of the gut microbiota, the blood group secretor type, and impact of the specific probiotic intervention on ADHD and AS?	Infants followed-up to 13 years old; 40 in the probiotic group and 35 in the placebo group (n = 75).	ADHD and AS	ADHD infants (53.3% received Lactobacillus rhamnosus GG, and 35 (46.7%) placebo during the first 6 mo of life were followed-up for 13 y. Children’s gut microbiota were evaluated at 3wk, 3, 6, 12, 18, 24 mo, and 13 years old.	Fluorescein in situ hybridization (FISH) and qPCR, and indirectly by determining the blood group secretor type at the age of 13 y.	No significant difference in gut microbiota in participants after intervention.	3 mo affected children had significantly lower median (IQR) with Bifidobacterium longum to compare with healthy children, (P = 0.045). 6 mo diagnosed children the number of Bifidobacteria were lower (P = 0.03). 18 mo the mean of Bacteroides and Lactobacillus-Enterococcus were lower in children with ADHD/AS (P = 0.0008, P = 0.01) 24 mo the numbers of Clostridium histolyticum cells were lower in affected children (P = 0.04). No significant difference in gut microbiota in 13 year old children.	Parent Assessment of Early Behavior Patterns: crying, sleeping, awake time, content, fussing, colic-type cry, and another cry across the study.	6 of 35 children who received a placebo had been diagnosed with ADHD (3 male, 4.0%) or AS (1 male 1.3%) or both ADHD and AS (2 male 2.7%). All of them received a placebo, and none of them were in the probiotic group by the age 13 y. Logistic regression was significant when it was controlled for gender (P = 0.02)	At the 6 month age, the SD of Bifidobacterium species in feces was higher in healthy children 9.12 (0.64) log cells/g than in diagnosed children 8.26 (1.24) log cells/g
Stevens et al. (2019)	How is the impact of the micronutrient treatment on the relative abundance of microbial diversity in children with ADHD symptoms?	Children between the 7–12 years old; 10 in the treatment group and 7 in the placebo group (n = 17).	ADHD	18 children diagnosed with ADHD enrolled in the 10-week pilot study: at 2, 4, 6, 8, and 10 weeks (or end of study). 10 children received a micronutrient treatment containing a formulation of vitamins, minerals, amino acids, and antioxidants, and 8 children received a placebo.	16S rRNA gene sequencing.	Micronutrient treatment did not drive large-scale changes in the composition or structure of the microbiome. Operational Taxonomic Unit’s (OTUs) significantly increased in the treatment group, and showed no meaningful difference in the placebo group.	Fresh microbiome samples were collected at baseline and ten weeks of study. OTUs significantly increased in the micronutrient children and presented no meaningful change in the placebo children.	Children’s Global Assessment Scale (CGAS)39 and ADHD Rating Scale IV (ADHD-RS-IV) -clinician	–	An overall trend supporting the observation that greater Bifidobacterium associated with a lower ADHD-IV-RS score, excepting post-micronutrient treatment where a low Bifidobacterium abundance was linked with a low ADHD-IV-RS score. Although, there was no significant association with C-GAS and ADHD-RS-IV score and low abundance of bacteria.
Grimaldi et al. (2017)	The main goal of this study was to investigate the impact of a prebiotic galactooligosqacchari (B-GOS) on gut microbial ecology metabolic end products of microbial fermentation. The in vitro gut model systems were inoculated with faecal samples.	3 male children with ASD and 3 non-autistic children (in age 5–10 years old) provided samples used in an in vitro gut model system (n = 6).	ASD	Supplementation of B-GOS to the in vitro gut model systems inoculated with faecal samples from autistic and non-autistic children.	Bacteriology composition analysis was assessed by using flow cytometry with fluorescence in situ hybridization FISH-FCM. Metabolic activity was examined by HPLC and H-NMR.	B-GOS implication significantly increased the number of Bifidobacterium spp. In autistic and non-autistic models.	The feacal samples from autistic group contained a greater number of Clostridium spp. but lower number of bifidobacteria in comparison to non-autistic models. B-GOS supplementation significaly increased number of bifidobacteria in both groups, and lactobacilli in the final vessel from non-autistic samples.	–	–	–
Grimaldi et al. (2018)	Evaluation of the impact of 6-week Bimuno galactooligosaccharide (B-GOS) prebiotic intervention and exclusion diets on children with ASD.	Children in range 4–11 years with formal diagnosis of Autism Spectrum Disorder completed the 10-week study (n = 26).	ASD	Participants (14 with un-restricted diet and 12 with exclusion diet) were divided to group who: I received placebo and II received B-GOS as a prebiotic intervention.	Bacterial enumeration was assessed by FISH analysis, 16sRNA gene amplicon sequencing, and metabolomics analysis by H-NMR to evaluate the urinary and faecal metabolomics profile in the different diet and after 6-weekB-GOS intervention.	After the intervention the number of Bifidobacterium spp. was greater but there was no significant difference after intervention and interactions between treatments and exclusion diet.	Participants with exclusion diet showed the significantly lower number of Bifidobacterium spp. and Veillonellaceae, and greater number of Faecalibacterium prausnitzii, Bacterioides spp. Moreover, in this group the significant correlation between types of bacteria and faecal amino acids has been found to compare with children on unrestricted diet. Group that received the B-GOD prebiotics presented significantly greater number of Lachnospiraceae family and changes in faecal and urine metabolomics profile.	Anxiety and ASD-related behavior questionnaires: Autism Treatment Evaluation Checklist (ATEC), Autism spectrum quotient (AQ), Empathy and systemising quotient (EQ-SQ), Spence’s Children Anxiety Scale-Parent version SCAS-, parents completed 5-day sleep diaries at baseline and after intervention.	Children with exclusion diet showed the significant lower scores of abdominal pain and bowel movement. Subjects received the B-GOD prebiotics were observed with improvements in anti-social behavior.	–
Parracho et al. (2010)	The aims of the study was to asses in children with Autism the effects of the probiotic (L. plantarum WCFS1) on the intestinal microbiota and gut function and to examine the effects on the behavior.	Children between 4 and 16 years of age finished the 12-week feeding study (n = 17).	ASD	A cross over study that included a 3-week placebo-feeding period, followed by a 3 week washed out period and 3 week probiotic feeding period.	Bacterial population levels were examined using fluorescence in situ hybridization (FISH)	No statistically significant sequence effect was observed in the groups.	The probiotic significantly increased numbers of lactobacilli/enterococci and decreased the clostridium cluster in the faecal microbiota of ASD children compared to the placebo.	Development Behavior Checklist (DBC) before the feeding study and at the end of each feed and washout period.	No significant difference was observed in the median scores for the five sub-scales between probiotic and placebo feeding. The baseline median scores were significantly higher (P < 0.05) for the probiotic feeding for disruptive/antisocial behavior, self-absorbed behavior, communication disturbance and anxiety problems.	The probiotic L. plantarum WCFS1 in ASD population, with modulation of the faecal microbiota observed, had a potential benefit in improved stool consistency and overall behavior scores (compared to baseline).
Sanctuary et al. (2019)	Objectives of this study include the assessment of tolerability of combination treatment with probiotic Bifidobacterium infantis with a bovine colostrum product (BCP) to compare BCP alone and assess the impact on GI symptoms, microbiome composition and immune factors in autistic children.	Children with ASD diagnosis and GI symptoms in age 2–11 completed both treatments (n = 8).	ASD	12-week cross-over study participants received during the first 5 weeks the probiotic B. infantis and prebiotic BCP supplementation, Followed by two-week washout period, and 5 weeks of supplementation only with BCP.	16S sequencing analysis and metabolomics measurement of faecal sample.	–	No significant differences in treatment effect on microbiota composition. Results suggest that probiotic-probiotic treatment (B. infantis and BCP) vs. only BCP treatment is well-tolerated in the study participants. Some of the participant from both groups reported improvement in chronic GI symptoms.	Aberrant Behavior Checklist (ABC), the Repetitive Behavior Scale-Revised (RBS-R), and the Adaptive Behavior Assessment System-Second Edition (ABAS-II)	Behavioral assessments: No difference in the adaptive behaviors. Significant decrease score were found in certain aberrant behaviors based on ABS questionnaire as: irritability (P = 0.003), stereotypy (P = 0.006), hyperactivity (P = 0.007), and total scores (P = 0.006 in BCP group, and for probiotic-probiotic group only in lethargy (P = 0.0499). No differences in adaptive behaviors were observed based on the ABAS-II questionnaire or repetitive behaviors based on the RBS-R.	The absence of global changing of the microbiome indicates there were no relationship between microbiome and outcomes.
Bahr et al. (2015)	The aim of this study was to asses if the use of risperidone (RSP) and secondary weight gain is associated with an altered gut microbiota.	Children between 9 and 15 years with chronic RSP treatment. Five new users of RSP and 10 psychiatric controls (n = 18).	Pediatric psychiatrically ill controls and users of RSP.	Follow up of risperidone taking patients up to 10 months.	16S rRNA sequencing	Chronic treatment with RSP was associated with an increase in body mass index and a significantly lower ratio of Bacteroidetes: Firmicutes as compared controls (ratio = 0.15 vs 1.24, respectively. P < 0.05)	There was a gradual decrease of the ratio Bacteroidetes: Firmicutes, in association with BMI gain.	–	–	–