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

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

New and Preliminary Evidence on Altered Oral and Gut Microbiota in Individuals with Autism Spectrum Disorder (ASD): Implications for ASD Diagnosis and Subtyping Based on Microbial Biomarkers

Autism Spectrum Disorder (ASD) is a complex neurological and developmental disorder characterized by behavioral and social impairments as well as multiple co-occurring conditions, such as gastrointestinal abnormalities, dental/periodontal diseases, and allergies. The etiology of ASD likely involves interaction between genetic and environmental factors. Recent studies suggest that oral and gut microbiome play important roles in the pathogenesis of inflammation, immune dysfunction, and disruption of the gut&ndash;brain axis, which may contribute to ASD pathophysiology. The majority of previous studies used unrelated neurotypical individuals as controls, and they focused on the gut microbiome, with little attention paid to the oral flora. In this pilot study, we used a first degree-relative matched design combined with high fidelity 16S rRNA (ribosomal RNA) gene amplicon sequencing in order to characterize the oral and gut microbiotas of patients with ASD compared to neurotypical individuals, and explored the utility of microbiome markers for ASD diagnosis and subtyping of clinical comorbid conditions. Additionally, we aimed to develop microbiome biomarkers to monitor responses to a subsequent clinical trial using probiotics supplementation. We identified distinct features of gut and salivary microbiota that differed between ASD patients and neurotypical controls. We next explored the utility of some differentially enriched markers for ASD diagnosis and examined the association between the oral and gut microbiomes using network analysis. Due to the tremendous clinical heterogeneity of the ASD population, we explored the relationship between microbiome and clinical indices as an attempt to extract microbiome signatures assocociated with clinical subtypes, including allergies, abdominal pain, and abnormal dietary habits. The diagnosis of ASD currently relies on psychological testing with potentially high subjectivity. Given the emerging role that the oral and gut microbiome plays in systemic diseases, our study will provide preliminary evidence for developing microbial markers that can be used to diagnose or guide treatment of ASD and comorbid conditions. These preliminary results also serve as a starting point to test whether altering the oral and gut microbiome could improve co-morbid conditions in patients with ASD and further modify the core symptoms of ASD