TABLE 3.
Mixed probiotic intervention studies.
| Authors | Study design | Treatment | Effect on gut microbiota | Effect on behavioral symptoms | Effect on GI symptoms |
| Tomova et al. (2015) | Real-time PCR on fecal samples of 10 children with autism before and after probiotic administration | A mixture of Lactobacilli, Bifidobacteria and Streptococci given 3 times a day for 4 months | Normalization of Bacteroides/Firmicutes ratio and Desulfovibrio spp. abundance; the count of Bifidobacterium and Desulfovibrio decreased significantly, and the absolute amount of Lactobacillus decreased (relative amount increased), reaching the level of healthy subjects | Decrease in ADI scores, and restrictive and stereotyped behavior were improved | − |
| Grossi et al. (2016) | Case report of a 12 years old boy with ASD and severe cognitive disability | A mixture of Bifidobacteria, Lactobacilli and Streptococci given daily for 4 weeks | − | Decrease in AODS-2 scores, and social behavior and neurosexual behavior were improved | GI symptoms improved |
| Shaaban et al. (2018) | Cohort study of 30 children with ASD from 5 to 9 years old | L. acidophilus, L. rhamnosus and B. longum for 3 months | The count of Bifidobacteria and Lactobacillus increased significantly | Decrease in ATEC scores, and speech/language communication, sociability, sensory/cognitive awareness and health/physical/behavior were improved | Decrease in 6-GSI scores |
| West and Roberts (2013) | Cohort study of 33 children with ASD | Delpro a and Del-Immune V b, for 21 days | − | Decrease in ATEC scores in 88% of children, and speech/language communication, sociability, sensory/cognitive awareness and health/physical/behavior were improved | Improvement of constipation and diarrhea, and GI symptoms improved |
| Arnold et al. (2019) | Randomized, double-blind, parallel, cross-controlled study of 10 ASD patients aged 3–12 years | Two groups were randomly assigned to receive 8 weeks each on VISBIOMEc and placebo separated by a 3-week washout | The relative abundance of Ruminococcaceae and Bifidobacteriaceae decreased, and the relative abundance of Bacteroidaceae and Verrucomicrobiaceae increased, but not significant | Decrease in ABC, CSHQ, PRAS-ASD, PSI and SRS scores, and the sleep problems were significantly improved | Decrease in PedsQL GI scores, and GI symptoms improved |
| Santocchi et al. (2020) | Randomized, double-blind, parallel, placebo-controlled study of 63 patients with ASD aged 18–72 months | Vivomixx® d vs. placebo, two pack once a day for the first month; Vivomixx® vs. placebo, one pack once a day for the next 5 months | − | Decrease in ADOS-CSS scores, but not significantly; decrease in ADOS-CSS and VABS II scores in non-GI, with social and communication skills significantly improved | Decrease in 6-GSI scores, and GI symptoms improved |
aDelpro® is a probiotic supplement, including Lactobacillus acidophilus, Lactobacillus casei, Lactobacillus delbrueckii, Bifidobacterium longum and Bifidobacterium bifidum.
bDel-Immune V® is a supplement containing stem fermentation cell lysate and DNA fragment of probiotic strain Lactobacillus rhamnosus V (DV strain).
cVISBIOME (VSL#3) is a probiotic supplement, including four strains of Lactobacilli (L. casei, L. plantarum, L. acidophilus and L. delbrueckii subsp. bulgaricus), three strains of Bifidobacteria (B. longum, B. infantis, and B. breve), one strain of Streptococcus thermophilus, and starch.
dVivomixx® is a probiotic supplement, and each packet contained 450 billions of eight probiotic strains, including Streptococcus thermophilus, Bifidobacterium breve, Bifidobacterium longum, Bifidobacterium infantis, Lactobacillus acidophilus, Lactobacillus plantarum, Lactobacillus paracasei, Lactobacillus delbrueckii subsp. Bulgaricus. ADI, Autism Diagnostic Interview; AODS-2, Autism Diagnostic Observation Schedule-2; CSHQ, Children’s Sleep Habits Questionnaire; PRAS-ASD, Parent-Rated Anxiety Scale for ASD; PSI, Parenting Stress Index; ADOS-CSS, Autism Diagnostic Observation Schedule – Calibrated Severity Score; VABS II, Vineland Adaptive Behavior Scales-Second Edition; 6-GSI, 6-Gastrointestinal Severity Index; PedsQL, Pediatric Quality of Life Inventory; ABC, Autism Behavior Checklist; ATEC, Autism Treatment Evaluation Checklist; GI, gastrointestinal; SRS, Social Responsiveness Scale.