Probiotics and Autism Research
Effects of Probiotic Supplementation on Gastrointestinal, Sensory and Core Symptoms in Autism Spectrum Disorders: A Randomized Controlled Trial
Authors:
Santocchi, E., Guiducci, L., Prosperi, M., Calderoni, S., Gaggini, M., Apicella, F., Tancredi, R., Billeci, L., Mastromarino, P., Grossi, E. and Gastaldelli, A.
Research study
Year
Type
Study size
Abstract
LINK/DOI
The microbiota-gut-brain axis has been recently recognized as a key modulator of neuropsychiatric health. In this framework, probiotics (recently named "psychobiotics") may modulate brain activity and function, possibly improving the behavioral profiles of children with Autism Spectrum Disorder (ASD). We evaluated the effects of probiotics on autism in a double-blind randomized, placebo-controlled trial of 85 preschoolers with ASD (mean age, 4.2 years; 84% boys). Participants were randomly assigned to probiotics (De Simone Formulation) (n=42) or placebo (n=43) for six months. Sixty-three (74%) children completed the trial. No differences between groups were detected on the primary outcome measure, the Total Autism Diagnostic Observation Schedule - Calibrated Severity Score (ADOS-CSS). An exploratory secondary analysis on subgroups of children with or without Gastrointestinal Symptoms (GI group, n= 30; NGI group, n=55) revealed in the NGI group treated with probiotics a significant decline in ADOS scores as compared to that in the placebo group, with a mean reduction of 0.81 in Total ADOS CSS and of 1.14 in Social-Affect ADOS CSS over six months. In the GI group treated with probiotics we found greater improvements in some GI symptoms, adaptive functioning, and sensory profiles than in the GI group treated with placebo. These results suggest potentially positive effects of probiotics on core autism symptoms in a subset of ASD children independent of the specific intermediation of the probiotic effect on GI symptoms. Further studies are warranted to replicate and extend these promising findings on a wider population with subsets of ASD patients which share targets of intervention on the microbiota-gut-brain axis.
85
Randomised controlled trial
2020
doi: 10.3389/fpsyt.2020.550593
Lactobacillus plantarum PS128 and Other Probiotics in Children and Adolescents with Autism Spectrum Disorder: A Real-World Experience
Authors:
Mensi, M.M., Rogantini, C., Marchesi, M., Borgatti, R. and Chiappedi, M.
Research study
Year
Type
Study size
Abstract
LINK/DOI
Autism Spectrum Disorder is a neurodevelopmental disorder. Recent data suggest that probiotics can reduce some symptoms of this disorder and Lactobacillus plantarum PS128 has been reported to be especially useful. We recruited a sample of 131 autistic children and adolescents (M:F = 122:19; age: 86.1 ± 41.1 months) and evaluated their changes after use of probiotics by mean of CGI. We found some significant improvements with very few side effects; these positive effects were more evident in younger children. Patients taking Lactobacillus plantarum PS128 had greater improvements and fewer side effects than those taking other probiotics. Our real-life data are consistent with existing literature showing a specific effect of Lactobacillus plantarum PS128 in Autism Spectrum Disorder.
131
Observational study
2021
doi: 10.3390/nu13062036
Characterization of Intestinal Microbiota and Probiotics Treatment in Children With Autism Spectrum Disorders in China
Authors:
Niu, M., Li, Q., Zhang, J., Wen, F., Dang, W., Duan, G., Li, H., Ruan, W., Yang, P., Guan, C. and Tian, H.
Research study
Year
Type
Study size
Abstract
LINK/DOI
Background:
Most previous studies have found that human intestinal microbiota affect the symptoms of autism spectrum disorder (ASD), especially gastrointestinal (GI) symptoms, but regarding this, there is limited data of non-western ethnicity. Probiotics can reconstitute the host intestinal microbiota and strengthen gastrointestinal function, however, clinical data proving the effect of probiotics treatment on ASD is lacking.
Methods:
This study explored the significant differences between ASD and neurotypical (NT), and the improvement of applied behavior analysis (ABA) training in combination with probiotics, vs. ABA training only. Results: We found significant differences between the ASD group and the NT group in the evenness of the intestinal microbiota and the relative abundance of the bacterial phyla and genus. At the phylum level, relative abundance of Bacteroidetes in the ASD group was significantly lower than in the NT group. At the genus level, the relative abundance of Bacteroides, Bifidobacterium, Ruminococcus, Roseburia, and Blautia in the ASD group was significantly lower than that in the NT group. After a 4-week ABA training program in combination with probiotics treatment, the ATEC and GI scores decreased more than the control group with ABA training only.
Conclusion:
Our findings suggest that intestinal microbiota is different between the NT children and the ASD children with or without GI problems. In combination with ABA training, probiotics treatment can bring more benefit to ASD children. Clinical trials with a more rigorous design and larger sample size are indispensable for further validation.
114
Randomised controlled trial
2019
doi: 10.3389/fneur.2019.01084
Precision microbial intervention improves social behavior but not autism severity: A pilot double-blind randomized placebo-controlled trial
Authors:
Mazzone, L., Dooling, S.W., Volpe, E., Uljarević, M., Waters, J.L., Sabatini, A., Arturi, L., Abate, R., Riccioni, A., Siracusano, M. and Pereira, M.
Research study
Year
Type
Study size
Abstract
LINK/DOI
Autism spectrum disorder (ASD) is characterized by the presence of restricted/repetitive behaviors and social communication deficits. Because effective treatments for ASD remain elusive, novel therapeutic strategies are necessary. Preclinical studies show that L. reuteri selectively reversed social deficits in several models for ASD. Here, in a double-blind, randomized, placebo-controlled trial, we tested the effect of L. reuteri (a product containing a combination of strains ATCC-PTA-6475 and DSM-17938) in children with ASD. The treatment does not alter overall autism severity, restricted/repetitive behaviors, the microbiome composition, or the immune profile. However, L. reuteri combination yields significant improvements in social functioning that generalized across different measures. Interestingly, ATCC-PTA-6475, but not the parental strain of DSM-17938, reverses the social deficits in a preclinical mouse model for ASD. Collectively, our findings show that L. reuteri enhances social behavior in children with ASD, thereby warranting larger trials in which strain-specific effects should also be investigated.
43
Double-blind, randomized, placebo-controlled pilot clinical trial
2024
doi: 10.1016/j.chom.2023.11.021
Efficacy and safety of Bacteroides fragilis BF839 for pediatric autism spectrum disorder: a randomized clinical trial
Authors:
Lin, C.H., Zeng, T., Lu, C.W., Li, D.Y., Liu, Y.Y., Li, B.M., Chen, S.Q. and Deng, Y.H.
Research study
Year
Type
Study size
Abstract
LINK/DOI
Background: The clinical utility of Bacteroides fragilis in treating autism spectrum disorder (ASD) remains unclear. Therefore, this randomized, double-blind, placebo-controlled study aimed to explore the therapeutic effects and safety of B. fragilis BF839 in the treatment of pediatric ASD.
Methods: We examined 60 children aged 2-10 years diagnosed with ASD, and participants received either BF839 powder (10 g/bar with ≥106 CFU/bar of viable bacteria, two bars/day) or placebo for 16 weeks. The primary outcomes was Autism Behavior Checklist (ABC) score. The secondary outcomes were Childhood Autism Rating Scale (CARS), Social Responsiveness Scale (SRS), Normal Development of Social Skills from Infants to Junior High School Children (S-M), Gastrointestinal Symptom Rating Scale (GSRS) scores, and fecal microbiome composition. Assessments were performed on day 0 and at weeks 8 and 16.
Results: Compared with the placebo group, the BF839 group showed significant improvement in the ABC body and object use scores at week 16, which was more pronounced in children with ASD aged <4 years. Among children with a baseline CARS score ≥30, the BF839 group showed significant improvements at week 16 in the ABC total score, ABC body and object use score, CARS score, and GSRS score compared to the placebo group. Only two patients (6.67%) in the BF839 group experienced mild diarrhea. Compared with baseline and placebo group levels, the BF839 group showed a significant post-intervention increase in abundance of bifidobacteria and change in the metabolic function of neuroactive compounds encoded by intestinal microorganisms.
Conclusion: BF839 significantly and safely improved abnormal behavior and gastrointestinal symptoms in children with ASD.
60
Randomised double blind placebo control study
2024
doi: 10.3389/fnut.2024.1447059
Impact of probiotic supplements on behavioural and gastrointestinal symptoms in children with autism spectrum disorder: A randomised controlled trial
Authors:
Khanna, H.N., Roy, S., Shaikh, A., Chhabra, R. and Uddin, A.
Research study
Year
Type
Study size
Abstract
LINK/DOI
Objective: To investigate whether probiotic supplementation can improve behavioural and gastrointestinal (GI) symptoms in children with autism spectrum disorder (ASD) aged 2-9 years and further explore the correlation between these symptoms.
Design: Single-blinded, randomised, placebo-controlled study.
Setting: Five developmental paediatric outpatient clinics of 'Continua Kids'.
Patients: Children aged 2-9 years diagnosed with ASD along with their caregivers.
Interventions: Probiotic or placebo sachet reconstituted in 50 mL of lukewarm milk/water, taken two times per day for 3 months.
Main outcome measures: Change in behavioural (measured by Social Responsiveness Scale-2 (SRS-2) and Aberrant Behaviour Checklist-2 (ABC-2) tools) and GI (measured by GI Severity Index (GSI) score) symptoms after receiving intervention for 3 months.
Results: A total of 180 children with ASD were enrolled in the study (probiotic group: 90 and placebo group: 90). All children completed the study. The probiotic group showed a significant reduction in behavioural symptom severity as measured by the SRS-2 tool (47.77% vs 23.33%; p=0.000) compared with the placebo. Probiotic-treated children demonstrated significant reductions in severe symptoms, including social withdrawal/lethargy (40%), stereotypic behaviour (37.77%), hyperactivity (34.44%) and inappropriate speech (32.22%) post-intervention (p=0.000). They also had marked improvements in constipation (p=0.003) and diarrhoea (p=0.043) compared with the placebo group. Both groups exhibited a statistically significant correlation between behavioural and GI symptoms.
Conclusions: Probiotic supplementation improved behavioural and GI symptoms in children with ASD with no adverse effects. Both symptoms were significantly correlated. However, these results need to be validated in a larger sample size.
180
Single-Blinded, Randomized, Placebo-Controlled Trial
2025
doi: 10.1136/bmjpo-2024-003045
The therapeutic effects of probiotics on core and associated behavioral symptoms of autism spectrum disorders: a systematic review and meta-analysis
Authors:
Lee, J.C., Chen, C.M., Sun, C.K., Tsai, I.T., Cheng, Y.S., Chiu, H.J., Wang, M.Y., Tang, Y.H. and Hung, K.C
Research study
Year
Type
Study size
Abstract
LINK/DOI
Background: We aimed at investigating the efficacies of probiotics in alleviating the core and associated symptoms of autism spectrum disorder (ASD).
Methods: Randomized placebo-controlled trials were identified from major electronic databases from inception to Nov 2023. The outcomes of interests including improvements in the total and associated symptoms of ASD were quantitatively expressed as effect size (ES) based on standardized mean difference (SMD) with 95% confidence interval (CI).
Results: Ten studies with 522 participants (mean age = 8.11) were included in this meta-analysis. The primary results revealed significant improvement in total symptoms in the probiotics group compared with the controls (SMD = - 0.19, p = 0.03, ten studies, n = 522) but not the core symptoms (i.e., repetitive restricted behaviors, As affiliations 3 and 5 are same, we have deleted the duplicate affiliations and renumbered accordingly. Please check and confirm.problems with social behaviors/communication). Subgroup analyses demonstrated improvement in total symptoms in probiotics users relative to their controls only in studies using multiple-strain probiotics (SMD = - 0.26, p = 0.03, five studies, n = 288) but not studies using single-strain regimens. Secondary results showed improvement in adaptation (SMD = 0.37, p = 0.03, three studies, n = 139) and an improvement trend in anxiety symptoms in the probiotics group compared with controls (SMD = - 0.29, 95% CI - 0.60 to 0.02, p = 0.07, three studies, n = 163) but failed to demonstrate greater improvement in the former regarding symptoms of irritability/aggression, hyperactivity/impulsivity, inattention, and parental stress.
Conclusions: Our study supported probiotics use against the overall behavioral symptoms of ASD, mainly in individuals receiving multiple-strain probiotics as supplements. However, our results showed that probiotics use was only associated with improvement in adaptation and perhaps anxiety, but not core symptoms, highlighting the impact of adaptation on quality of life rather than just the core symptoms. Nevertheless, the limited number of included trials warrants further large-scale clinical investigations.
522
Sytematic review and meta-analysis
2024
doi: 10.1186/s13034-024-00848-3
Effects of Probiotics on Autism Spectrum Disorder in Children: A Systematic Review and Meta-Analysis of Clinical Trials
Authors:
He, X., Liu, W., Tang, F., Chen, X. and Song, G.
Research study
Year
Type
Study size
Abstract
LINK/DOI
Many studies have explored the efficacy of probiotics on autism spectrum disorder (ASD) in children, but there is no consensus on the curative effect. This systematic review and meta-analysis aimed to comprehensively investigate whether probiotics could improve behavioral symptoms in children with ASD. A systematic database search was conducted and a total of seven studies were included in the meta-analysis. We found a nonsignificant overall effect size of probiotics on behavioral symptoms in children with ASD (SMD = -0.24, 95% CI: -0.60 to 0.11, p = 0.18). However, a significant overall effect size was found in the subgroup of the probiotic blend (SMD = -0.42, 95% CI: -0.83 to -0.02, p = 0.04). Additionally, these studies provided limited evidence for the efficacy of probiotics due to their small sample sizes, a shorter intervention duration, different probiotics used, different scales used, and poor research quality. Thus, randomized, double-blind, and placebo-controlled studies following strict trial guidelines are needed to precisely demonstrate the therapeutic effects of probiotics on ASD in children.
268
Systematic review and meta-analysis
2023
doi: 10.3390/nu15061415
The role of probiotics in children with autism spectrum disorder: A prospective, open-label study
Authors:
Shaaban, S.Y., El Gendy, Y.G., Mehanna, N.S., El-Senousy, W.M., El-Feki, H.S., Saad, K. and El-Asheer, O.M.
Research study
Year
Type
Study size
Abstract
LINK/DOI
Objective:
There are limited data on the efficacy of probiotics in children with ASD, therefore, this study aims to evaluate the efficacy and tolerability of probiotics in an Egyptian cohort of children with ASD.
Methods:
Gastrointestinal (GI) flora were assessed by quantitative real-time PCR of stool samples of 30 autistic children from 5 to 9 years old. GI symptoms of autistic children were assessed with a modified six-item Gastrointestinal Severity Index (6-GSI) questionnaire, and autistic symptoms were assessed with Autism Treatment Evaluation Checklist (ATEC) before and after 3 months of supplementation of probiotics nutritional supplement formula (each gram contains 100 × 106 colony forming units of three probiotic strains; Lactobacillus acidophilus, Lactobacillus rhamnosus and Bifidobacteria longum).
Results:
After probiotic supplementation, the stool PCR of autistic children showed increases in the colony counts of Bifidobacteria and Lactobacilli levels, with a significant reduction in their body weight as well as significant improvements in the severity of autism (assessed by the ATEC), and gastrointestinal symptoms (assessed by the 6-GSI) compared to the baseline evaluated at the start of the study.
Conclusions:
We concluded that probiotics have beneficial effects on both behavioral and GI manifestations of ASD. Probiotics (a non-pharmacological and relatively risk-free option) could be recommended for children with ASD as an adjuvant therapy. At this stage, this study is a single center with a small number of patients and a great deal of additional wide-scale randomized controlled trials are needed to critically confirm the efficacy of probiotics in ASD.
30
Prospective open label study
2018
doi: 10.1080/1028415X.2017.1347746
