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

Table 8 Characteristics of included synbiotic studies in autism spectrum disorder

Ref.	Study design	Participants (n)	Age range	Synbiotic intervention	Duration	Main outcomes assessed	Key findings
Sanctuary et al[21]	Randomized double-blind crossover pilot study	8 children with ASD and GI symptoms	2-11 years	Bifidobacterium infantis + bovine colostrum product (prebiotic oligosaccharides)	12 weeks (5 weeks synbiotic + washout + 5 weeks prebiotic alone)	Gastrointestinal symptoms, behavioral symptoms, and inflammatory markers	Combination treatment was well tolerated and associated with reduced GI symptoms and some improvements in aberrant behaviors; decreases in IL-13 and TNF-α were observed in some participants. Symbiotics
Wang et al[20]	Controlled intervention study	26 children with ASD (16 synbiotic, 10 placebo)	2-8 years	Probiotics + FOS	30, 60, and 108 days	Autism severity, gut microbiota composition, SCFAs, neurotransmitters	Synbiotic treatment increased beneficial bacteria (Bifidobacterium longum), elevated SCFAs, normalized serotonin and dopamine metabolites, and significantly reduced autism and GI symptom severity. Symbiotics
Schmitt et al[29]	Randomized double-blind placebo-controlled crossover trial	15 participants with ASD	15-45 years	SB-121 synbiotic (Limosilactobacillus reuteri + dextran microparticles + maltose)	28-day treatment periods	Adaptive behavior (Vineland-3), social preference, safety	Significant improvement in Vineland-3 Adaptive Behavior Composite score (P = 0.03) and trends toward improved social preference; treatment was safe and well tolerated. Symbiotics
Phan et al[42]	Open-label clinical study	170 ASD participants completed the study	10.4 ± 7.1 years	Precision synbiotic formulation targeting microbiome diversity	3 months	ASD symptoms, GI symptoms, and metagenomic microbiome profiling	Synbiotic supplementation increased microbiome diversity and improved GI discomfort and several ASD-related symptoms including language, cognition, and communication. Symbiotics
Mitchell et al[44]	Randomized pilot trial	40 children with ASD	5-10 years	Synbiotics alone vs synbiotics + gut-directed hypnotherapy	12 weeks (24-week follow-up)	GI symptom scores, behavior, anxiety, microbiome composition	Both groups showed significant reductions in GI symptoms (P < 0.001); the combined therapy group also showed additional reductions in anxiety and irritability. Symbiotics
Wong et al[43]	Open-label pilot study	30 children with ASD	Mean age 82 years	SCM06 synbiotic formulation	12 weeks	Anxiety, sensory hyperresponsiveness, abdominal pain, microbiome metabolomics	Significant improvements in anxiety, sensory hyperresponsiveness, and abdominal pain; increases in Bifidobacterium pseudocatenulatum and SCFAs were observed. Symbiotics

ASD: Autism spectrum disorder; FOS: Fructo-oligosaccharides; GI: Gastrointestinal; IL-13: Interleukin-13; SB-121: Investigational synbiotic formulation SB-121; SCFAs: Short-chain fatty acids; TNF-α: Tumor necrosis factor alpha.