A Randomized, Double-Blind, Placebo Controlled Trial of 4 Weeks Intervention with Lactobacillus Plantarum PS128 in Autism Spectrum Disorder Boys in Taiwan
Objectives: To investigate the effects of PS128 on boys with autism spectrum disorders.
Methods: Eighty male subjects diagnosed with autism spectrum disorder and confirmed with Autism Diagnostic Interview-Revised (ADI-R) were included in a 4-week, randomized, double-blind, placebo-controlled trial with PS128 or placebo (microcrystalline cellulose) intervention. The subjects took PS128 (3×1010 CFU) or microcrystalline cellulose (300 mg) orally twice daily. Several questionnaires were measured at baseline and day28 including Autism Behavior Checklist-Taiwan Version, (ABCT), Social Responsiveness Scale (SRS), SNAP-IV and child behavior checklist (CBCL). The principle of investigator measured Clinical Global Impressions (CGI)-severity scale was measured on day1 and Clinical Global Impressions (CGI)-improvement scale on day28. The primary outcome measure was ABCT. Fecal sample of subjects were collected on baseline and day28. Fecal levels of inflammatory molecules were analyzed by ELISA. Gut microbiota was analyzed by Next Generation Sequencing techniques. This study was registered on the Australian New Zealand Clinical Trials Registry (ANZCTR; Trial ID: ACTRN12616001002471).
Results: Four subjects of placebo group and 2 subject of PS128 group were dropped-out (drop-out rates is 7.5%) in this study. There is no adverse effect occurred in this study. There were no significant differences between in terms of subjects’ age, education and their caregiver's education. It was also no significant difference with baseline performance between two groups with ADI-R, ABCT, SRS, SNAP-IV and CBCL scores. By the end of 4 weeks, the scores of Body and object use in ABCT and Rule-Breaking Behavior in CBCL were decreased significantly in PS128 group (p < 0.05). However, the placebo group was failed to improve significantly on any efficacy measure. Fecal levels of inflammatory molecules, myeloperoxidase and calprotectin, and gut permeability marker, zonulin, were similar in both groups on day1 and day28. NGS analysis results showed significant increasement of Lactobacillus was observed in PS128 group.
Conclusions: PS128 (3×1010 CFU) twice daily for 4 weeks significantly improved the scores of Body and object use in ABCT and Rule-Breaking Behavior in CBCL. Alteration of gut microbiota may contribute at least partially to the improvement.