Probiotics for Gastrointestinal Symptoms and Quality of Life in Autism: A Placebo-Controlled Pilot Trial

Abstract

Objective: A randomized pilot trial of gastrointestinal (GI) symptoms targeting probiotic for quality of life in autism spectrum disorder (ASD). Methods: Thirteen children, 3-12 years of age with ASD, anxiety, and GI symptoms, were randomized into a probiotic crossover trial of 8 weeks each on VISBIOME and placebo separated by a 3-week washout. VISBIOME contains eight probiotic species, mostly Lactobacillus and Bifidobacterium. Primary outcome was the Pediatric Quality of Life Inventory (PedsQL) GI module. Secondary outcomes included gut microbiota analysis, the Parent-Rated Anxiety Scale for ASD (PRAS-ASD), and parent-selected target symptoms. A mixed analysis model was applied. Results: Thirteen children were randomized, with 10 completing the study (77% retention): 6 in probiotic/placebo sequence, 4 in placebo/probiotic sequence. Adherence to study treatment was 96%. There were no serious adverse events (AEs), and more nonserious AEs occurred with placebo than with probiotic, including those attributable to treatment. Only 6 of the 10 guessed the correct treatment at the end of week 8. Over the 19-week trial, each outcome improved from baseline and PedsQL correlated significantly with abundance of Lactobacillus without discernable changes to microbiota composition/diversity. Although probiotic showed more improvement than placebo, PedsQL and PRAS-ASD were not statistically significant, as expected at this sample size. PedsQL effect size was d = 0.49 by the general model and d = 0.79 by simple comparison of week 8 changes. A parent-selected target symptom showed significant improvement in GI complaints on probiotic compared with placebo (p = 0.02, d = 0.79). Probiotic effects carried over through the 3-week washout. Conclusion: The VISBIOME formulation was safe and suggested a health benefit in children with ASD and GI symptoms who retained Lactobacillus. The moderate effect size compared with placebo warrants a larger trial using a parallel-group design.

Keywords: anxiety; autism; autism spectrum disorder; gastrointestinal problems; probiotics; quality of life.

FIG. 1.

Primary outcome, Pediatric Quality of Life GI Module, over the course of both conditions by sequence group. Higher score is better. Vertical dotted lines delineate the 3-week washout between conditions. Difference at 11 weeks is significant (p = 0.006). GI, gastrointestinal; PS, placebo first; SP, probiotic supplement first. Color images are available online.

FIG. 2.

Microbiota community dynamics following VISBIOME treatment. (A) Shannon H diversity index does not show significant alterations following probiotic or placebo. (B) Relative family abundance does not show a significant difference over the course of both conditions by sequence group. (C) Lactobacillus correlation with the PedsQL score with an exponential curve fit. Regression analysis shows a significant correlation; Spearman's Rho = 0.573579609, p = 0.022 after applying Benjamini–Hochberg multiple testing correction. PedsQL, Pediatric Quality of Life Inventory; PS, placebo first; SP, probiotic supplement first. Color images are available online.