Psychobiotics in pediatric autism spectrum disorder: A systematic review of efficacy, mechanisms, and clinical translation

Table 10 Characteristics of included studies investigating fecal microbiota transplantation in autism spectrum disorder

Ref.	Study design	Participants	FMT type/delivery	Outcomes assessed	Main findings
Wang et al[45]	Randomized double-blind placebo-controlled trial	41 children with ASD (39 boys and 3 girls, aged 4-12 years)	FMT vs placebo	GSRS, CARS, ABC, SRS; urinary metabolites	Significant improvements after FMT: GSRS decreased (30.17 → 19), CARS (36.22 → 33.33), SRS (151.17 → 137.5), ABC (76.39 → 53.17). Urinary 5-HIAA decreased, suggesting altered serotonin metabolism
Liu et al[53]	Prospective interventional study	24 ASD children initially; 18 second course; 13 third; 8 fourth	Fresh WMT	ASD symptoms, sleep disorder, constipation, microbiome metabolites	WMT improved behavioral symptoms, sleep disturbances, and constipation. Microbiome shifts included ↓Bacteroides, Flavonifractor, Parasutterella and ↑Prevotella
Chen et al[54]	Microbiome mechanistic study within FMT clinical dataset	ASD patients with GI comorbidities	Encapsulated FMT	Metagenomic microbial dynamics	Donor-recipient microbial interactions influenced subspecies transfer and clinical response, suggesting microbial compatibility affects FMT success
Li et al[47]	Prospective single-arm study	98 children with ASD	FMT via capsules, transendoscopic enteral tube, or nasojejunal tube	ABC, CARS, SRS, GSRS, SDSC; adverse events	Improvements in ASD symptoms, GI symptoms, and sleep disturbances. Capsules and nasojejunal tube showed greater symptom reduction than transendoscopic enteral tube. No serious adverse events
Li et al[48]	Prospective clinical study	38 ASD children; 30 healthy controls	Oral lyophilized FMT (every 4 weeks for 12 weeks)	ABC, CARS, SRS, SDSC; microbiome composition	After treatment: ABC ↓23%, CARS ↓10%, SRS ↓6%, SDSC ↓10%. Gut bacterial and fungal composition shifted toward healthier profiles
Li et al[49]	Open-label clinical trial	40 children with ASD (age 3-17 years)	FMT	GI symptoms, ASD symptoms, gut microbiota, neurotransmitters	FMT improved GI and behavioral symptoms, altered serum neurotransmitters, and promoted colonization of donor microbes
Pan et al[50]	Retrospective study	55 Children with ASD (median age: 6 years, 80.95% were male)	Repeated WMT	ABC, CARS, SDSC, GI symptoms, and inflammatory markers	WMT improved ASD symptoms, GI symptoms, and sleep disorders. Multiple treatment courses produced greater improvements
Zhang et al[51]	Retrospective observational study	49 children with ASD	WMT	Sleep disturbance (SDSC), stool characteristics (BSFS)	WMT improved sleep disorders and constipation; behavioral symptoms also improved with no serious adverse events
Kang et al[46]	Open-label clinical trial	18 children with ASD	Microbiota transfer therapy (antibiotics + bowel cleanse + FMT)	GI symptoms, ASD behavioral measures, microbiome	80% reduction in GI symptoms and significant improvements in ASD behaviors; increased bacterial diversity and beneficial taxa
Kang et al[52]	Long-term follow-up study	Same 18 participants from the previous trial	Microbiota transfer therapy	GI symptoms, ASD symptoms, gut microbiota	Improvements in GI symptoms and ASD behaviors were maintained for 2 years, with sustained microbiome changes

ABC: Aberrant Behavior Checklist; ASD: Autism spectrum disorder; BSFS: Bristol Stool Form Scale; CARS: Childhood Autism Rating Scale; FMT: Fecal microbiota transplantation; GI: Gastrointestinal; GSRS: Gastrointestinal Symptom Rating Scale; MTT: Microbiota transfer therapy; SDSC: Sleep Disturbance Scale for Children; SRS: Social Responsiveness Scale; WMT: Washed microbiota transplantation.