Two-stage pilot RCT protocol testing L. reuteri probiotics (12 weeks) followed by added oxytocin nasal spray (12 more weeks) for social deficits in 60 ASD patients.
60 patients, 24 weekspilot trial testing whether probiotics can enhance oxytocin therapy for autism social deficits through the gut-brain axis
What the researchers found
This is a protocol for a two-stage pilot randomized controlled trial. In stage one (weeks 0-12), 60 ASD patients receive either oral L. reuteri probiotics or placebo. In stage two (weeks 13-24), all participants also receive intranasal oxytocin spray.
Primary outcomes include serum oxytocin levels, social behavior scores (Autism Behavior Checklist, Social Responsiveness Scale), an emotional facial matching test, and eye-tracking. Secondary outcomes include GI function, gut microbiome composition, and short-chain fatty acid levels.
The rationale is based on animal studies showing L. reuteri increases oxytocin levels and improves social behavior in ASD mouse models. Intranasal oxytocin has shown some promise in improving social functioning in ASD patients.
Why it matters
Autism spectrum disorder has no FDA-approved treatments targeting core social deficits. Both oxytocin and gut-brain interventions are promising but understudied. This trial is innovative because it tests whether a probiotic can boost the body's own oxytocin production and whether combining it with intranasal oxytocin produces additive benefits.
The gut-brain-behavior connection in autism is a rapidly growing research area.
The numbers in context
60 participants; 24 weeks; 2-stage design; probiotics for 24 weeks, oxytocin added at week 13
How the study worked
This is a trial protocol, not a results paper. The design is a two-stage, randomized, double-blind, placebo-controlled, parallel-group pilot study. Sixty participants with ASD will be enrolled. Outcomes are assessed at baseline, week 12, and week 24.
Who was studied
Patients with autism spectrum disorder (planned)
What this study cannot tell us
This is a protocol paper, not a results paper. The trial had not yet reported outcomes at the time of publication. As a pilot study with 60 participants, it is designed to test feasibility rather than prove efficacy.
The two-stage design means the probiotic effect cannot be fully separated from the oxytocin effect in the second stage.
How to read the evidence
Not applicable — this is a protocol paper, not a results paper. The trial design is sound but outcomes have not been reported.
When this study was published
Published in 2020. Trial results may have been published since.
The bigger picture
Autism has no approved treatment for core social deficits. Both oxytocin and gut-brain interventions show promise individually. This trial innovatively tests whether probiotics can boost oxytocin levels naturally and enhance the effect of exogenous oxytocin.
Questions still open
- Do L. reuteri probiotics actually increase serum oxytocin levels in ASD patients?
- Will the two-stage design distinguish probiotic effects from oxytocin effects?
- Is 60 participants enough to detect meaningful social improvements?
Common questions
Could probiotics help with autism?
When will results be available?
Read the original research
Probiotics and oxytocin nasal spray as neuro-social-behavioral interventions for patients with autism spectrum disorders: a pilot randomized controlled trial protocol.
Pilot and feasibility studies, 6, 20
Citation
Kong, Xue-Jun; Liu, Jun; Li, Jing; Kwong, Kenneth; Koh, Madelyn; Sukijthamapan, Piyawat; Guo, Jason J; Sun, Zhenyu Jim; Song, Yiqing. (2020). Probiotics and oxytocin nasal spray as neuro-social-behavioral interventions for patients with autism spectrum disorders: a pilot randomized controlled trial protocol.. Pilot and feasibility studies, 6, 20. https://doi.org/10.1186/s40814-020-0557-8