TABLE 4.

Intervention studies of prebiotics and probiotics combined with prebiotics.

Authors	Study design	Treatment	Effect on gut microbiota	Effect on behavioral symptoms	Effect on GI symptoms
Grimaldi et al. (2018)	Randomized, double-blind, placebo-controlled study of 30 ASD patients aged 4–11 years	B-GOS, for 6 weeks	The diversity of gut microbiota increased, but there was no significant difference; the relative abundance of Bifidobacterium and Veillonellaceae decreased, while the relative abundance of Faecalibacterium prausnitzii and Bacteroides increased	Decrease the antisocial behavior score in ATEC; improve the sleep quality score in SCAS-P; decrease in AQ scores only for ASD patients on a restricted diet (gluten free casein free diet)	GI symptoms improved
Inoue et al. (2019)	Cohort study of 13 ASD patients aged 4–9 years	6 g PHGG every day, for 2 months or more	The relative abundance of Acidaminococcus and Blautia increased, while the relative abundance of Streptococcus, Odoribacter and Eubacterium decreased	Decrease the irritability subscale score in ABC-J	GI symptoms improved
Sanctuary et al. (2019)	Randomized, double-blind, cross-controlled study of 8 ASD patients with GI aged 2–11 years	Two groups were randomly assigned to receive 5 weeks each on the BCP alone and the combination of Bifidobacterium infantis and BCP separated by a 2-week washout	−	Decrease in ABC scores, especially when stereotyping behavior and sleep problems were improved, but the improvement was more pronounced when prebiotics were taken alone	Decrease in QPGS-RIII and GIH scores, and GI symptoms improved
Wang et al. (2020)	Randomized, double-blind, placebo-controlled study of 26 ASD patients aged 3–9 years	The combination of probiotics①and FOS vs. placebo, for 108 days	The relative abundance of Bifidobacteriales and B. longum increased, while the relative abundance of some harmful bacteria decreased, such as Clostridium and Ruminococcus	After the first 30 days, decrease in ATEC scores, but not significant; after the 30–60 days, decrease significant in ATEC scores	Decrease significant in 6-GSI scores, and GI symptoms improved

B-GOS^®, Bimuno^® galactooligosaccharide; PHGG, Partially hydrolyzed guar gum; BCP, Bovine colostrums powder; Probiotics①, is a probiotic blend, including Bifidobacterium infantis Bi-26, Lactobacillus rhamnosus HN001, Bifidobacterium lactis BL-04 and Lactobacillus paracasei LPC-37; FOS, fructooligosaccharide; SCAS-P, Spence’s Children Anxiety Scale-Parent version; AQ, Autism Spectrum Quotient; ABC-J, Aberrant Behavior Checklist, Japanese Version; QPGS-RIII, Questionnaire on Pediatric Gastrointestinal Symptoms-Rome III Version; GIH, Gastrointestinal History; ABC, Autism Behavior Checklist; ATEC, Autism Treatment Evaluation Checklist; GI, gastrointestinal; 6-GSI, 6-Gastrointestinal Severity Index.