Table 2.

Various probiotics and prebiotics used in the management of autism.

Category	Name of strain and marketed formulations	Study type	Dose	Duration of intervention	Dosage form	Outcomes	Reference
Probiotic	1) Children Dophilus: blend of 3 strains of lactobacillus (60%), 2 strains of Bifidobacterium (25%), 1 strain of Streptococcus (15%)	A non- controlled trial conducted in Slovakia on 29 Children: 10 ASD, 9 non-ASD siblings, 10 ASD controls	3 times/day	4 months	–	Probiotic supplementation elicited:	39,100
						a)Decreased levels of Clostridium (hence propionate and p-cresol) will be reduced.
						b)A strong correlation was established between TNF-α concentrations and GI symptoms. A significant reduction in TNF-α was reported on administering probiotic therapy.
						c)Reduction in severity of ASD symptoms but the results were not significant.
						The following diagnostic scales were used for assessment of these symptoms: Autism Diagnostic Interview (ADI): Childhood Autism Rating Scale (CARS); Total Behavior Problem Score (TBPS)
	2) Delpro capsule: Lactobacillus delbrueckii, L. acidophilus, Lactobacillus casei, B. longum, Bifidobacteriumbifidum (along with an additional 8 mg Del-immune V powder)	A noncontrolled trial conducted in USA on 33 Children with ASD in age group of 3–16 years.	10 billion Colony forming units (CFUs) total (1 capsule, 3 times/day)	21 days	Capsule	A significant decrease across all ATEC (Autism Treatment Evaluation Checklist) domain scores including speech, communication language, sociability, sensory/cognitive awareness, health/physical/behavior. Childhood Autism Rating Scale was used for the evaluation of symptoms.	100
	3) Vivomix probiotic: S. thermophilus, B. breve, B. longum	Randomized placebo controlled trial of a group of 100 children	–	5 months	Water soluble formula for oral consumption	a)Change in level of severity of ASD modification in cognitive behavior and language development, improved GI symptoms, changes in behavioral profiles (Childhood Autism Rating Scale and Repetitive Behavior Scale-Revised (RBS-R were used to assess the symptoms).	39,101
						b)Increased Bifidobacterium levels that improves impaired gut permeability
	4) Protein R: mixture of Bifidobacteria and Lactobacilli strain.	50 young male hamsters weighing between 60 and 70 g in which autistic like behaviors were induced by clindamycin and propionic acid administration.	2 × 108 CFU/day	27 days	–	a)Reduces the autistic symptoms like excitation, inhibition, imbalance in hamsters.	13,102
						b)Bifidobacteria and Lactobacillus restores altered GABA levels in autistic children.
	5) 3 strain: L. acidophilus, Lactobacillus rhamnosus, B. Longum	Trial in Egypt of 60 children, aged between 5 and 9 years.	5 g of powder/day (each gram contains 100 × 106 CFUs of each strain.	1 time/day for 3 months.	–	(a)After probiotic supplementation, significant increase in colony count of Bifidobacterium and Lactobacillus.	18,25,90,103
						(b)Lactobacillus and Bifidobacterium showed anti-inflammatory action by stimulating IL-10 release and also synthesize GABA (which was altered due to dysbiosis).
						(c)Improvement in GI symptoms (reduction in constipation, flatulence, abdominal pain)
						(d)Improvement in autistic behavioral symptoms (improved communication, language/speech problems, physical behavior). These symptoms were evaluated using Childhood Autism Rating Scale.
	6) VISBIOME probiotic: S. thermophillus, B. breve, B. longum, B. infantis, L. acidophilus, L. plantarum, Lactobacillus paracasei, Lactobacillus delbruecki subsp. Bulgaricus.	Randomized crossover trial with 13 children.	–	19 weeks	Available in powder packets (each containing 900 billion bacteria).	a)Improved gastrointestinal symptoms of autism and the formulation was found to be safe and suggested a health benefit in children with ASD. L. plantarum improved anti-social behavior, anxiety and communication problems which were evaluated by Social Responsiveness Scale (SRS) and Children's Sleep Habits Questionnaire (CSHQ).	13,60,87,103, 104, 105
						b)L. plantarum led to increased levels of Lactobacilli/enterococci and decrease in Clostridium. As Clostridium synthesizes propionate which can lead to autistic symptoms as mentioned earlier so reduction in propionate will produce beneficial effects.
						c)B. Infantis resulted in the elevation of tryptophan levels (that was earlier reduced in autism).
	7) L. acidophilus	A non- controlled trial in Poland of 22 children with ASD aged between 4 and 10 years.	5 × 1010 CFUs 2 times/day	2 months	–	a)Urine DA (D-arabinitol)-to-LA (L-arabinitol) ratio (a marker of invasive Candidiasis) decreased from a mean of 3.14 ± 0.14 before probiotic treatment to a mean of 2.77 ± 0.28 after probiotic treatment.	88,100
						b)Changes in ASD symptoms, improvement in the ability to concentrate and to carry orders were assessed by Autism Treatment Evaluation Checklist (ATEC).
	8) Lactobacillus rhamnosus	Randomized trial, placebo control in Finland on 15 infants for 6 months of life and followed for 13 years starting at the age of 6 month.	–	First 6 months of life.	Capsule	a)Probiotic supplementation early in life reduces the risk of neuropsychiatric disorders development later in childhood and also change the gut microbiota composition. It regulates emotional behavior, the central GABAergic system which is associated with neuropsychiatric disorder; also prevent learning and memory dysfunction.	13,106
						b)It also shows anti-inflammatory property by inducing high IL-10 (which inhibits the release of inflammatory cytokines).
Prebiotics	1(B-GOS) Bimuno-galactooligosaccharide	Double blind placebo controlled, crossover study, 83 subjects from general population with GI symptoms.	2.75 g/day	2 weeks	Supplied in sachets containing powder form.	Resulted in lower scores of abdominal pain and bowel movement as well as lower abundance of Bifidobacterium, higher presence of Faecali bacterium prausnitzii and Bacteroides spp.	107
	2) Short chain glactooligosacharide (scGOS), long chain fructooligosaccharide (lcFOS).	Trial on healthy BALB/c mice from day of birth	9 parts of scGOS:1 part of lcFOS (w/w) administered from the day of birth	–	–	Reduce anxiety, stereotypic behavior and improve social behavior in adulthood.	108