Probiotic and Oxytocin Combination Therapy in Patients with Autism Spectrum Disorder: A Randomized, Double-Blinded, Placebo-Controlled Pilot Trial

Abstract

Autism spectrum disorder (ASD) is a rapidly growing neurodevelopmental disorder. Both probiotics and oxytocin were reported to have therapeutic potential; however, the combination therapy has not yet been studied. We conducted a randomized, double-blinded, placebo-controlled, 2-stage pilot trial in 35 individuals with ASD aged 3–20 years (median = 10.30 years). Subjects were randomly assigned to receive daily Lactobacillus plantarum PS128 probiotic (6 × 1010 CFUs) or a placebo for 28 weeks; starting on week 16, both groups received oxytocin. The primary outcomes measure socio-behavioral severity using the Social Responsiveness Scale (SRS) and Aberrant Behavior Checklist (ABC). The secondary outcomes include measures of the Clinical Global Impression (CGI) scale, fecal microbiome, blood serum inflammatory markers, and oxytocin. All outcomes were compared between the two groups at baseline, 16 weeks, and 28 weeks into treatment. We observed improvements in ABC and SRS scores and significant improvements in CGI-improvement between those receiving probiotics and oxytocin combination therapy compared to those receiving placebo (p < 0.05). A significant number of favorable gut microbiome network hubs were also identified after combination therapy (p < 0.05). The favorable social cognition response of the combination regimen is highly correlated with the abundance of the Eubacterium hallii group. Our findings suggest synergic effects between probiotics PS128 and oxytocin in ASD patients, although further investigation is warranted.

Fecal Microbiota Transplantation Relieves Gastrointestinal and Autism Symptoms by Improving the Gut Microbiota in an Open-Label Study

“…Recent studies have shown that the gut microbiota is involved in the bidirectional regulation of the intestinal and central nervous systems through neural, endocrine, metabolic, and immune pathways ( Osadchiy et al, 2019 ). It is believed that microecological therapies that improve the gut microbiota can alleviate some gastrointestinal symptoms and ASD symptoms in ASD patients, so far, some reports have already proved that gut microbiota intervention therapy is helpful for ASD improvement ( Wang et al, 2020 ; Kong et al, 2021 ).…”

Effects of Lactobacillus plantarum PS128 on Depressive Symptoms and Sleep Quality in Self-Reported Insomniacs: A Randomized, Double-Blind, Placebo-Controlled Pilot Trial

“…The probiotic product has been reported to ameliorate anxiety, hyperactivity, impulse, and opposition/defiance behaviors [ 47 ], and has more positive effects in children than adolescents with ASD [ 48 ]. Combined with oxytocin treatment, PS128 increases ASD patients’ favorable gut microbiome network hubs [ 49 ]. Furthermore, it may have a potential benefit for mood disorders, as the main finding of this study suggested that PS128 may be able to reduce depressive symptoms in insomniacs.…”

Alteration of Gut Microbiota: New Strategy for Treating Autism Spectrum Disorder

“…In line with this study, Mensi et al, 2021 found that autistic children and adolescents who received L. plantarum PS128 had greater improvements in terms of global functioning characterized by increased attention, communication skills, and personal autonomies. In another randomized, double-blind, placebo-controlled pilot trial, individuals with ASD aged 3–20 years who received oral probiotic L. plantarum PS128 and intranasal oxytocin elicited significant improvements in ASD core socio-behavioral symptoms, clinical global functioning, and gut microbiome dysbiosis ( Kong et al, 2021c ). It was revealed that the two treatments are supposed to have synergistic interactions in the regulation of the gut–brain axis.…”