Probiotic and intra-nasal oxytocin combination therapy on autonomic function and gut-brain axis signaling in young children and teens with autism spectrum disorder.

Autonomic dysfunction has been widely studied in individuals with autism spectral disorder (ASD); however, the autonomic response to probiotic and oxytocin (OT) combination intervention has not yet been explored. We conducted the present study that includes 35 individuals with ASD aged 3-20 years to explore autonomic responses to daily Lactobacillus plantarum probiotic supplementation and OT nasal spray treatment both alone and in combination. We identified significant improvements in autonomic indices from subjects receiving combination treatment relative to those receiving placebo. Parameters that were observed to improve following combination treatment are time domain metrics of heart rate variability (HRV), including the root mean square of successive differences between normal heartbeats (RMSSD), standard deviation of normal-to-normal R-R intervals (SDNN), and proportion of the number of pairs of adjacent NN intervals that differ by more than 50ms (pNN50, p < 0.05). Furthermore, individuals that received either probiotics or OT alone demonstrated fewer changes in RMSSD, pNN50, and SDNN. Several parameters that demonstrated significant improvements in combination therapy were found to be correlated with baseline levels of OT (LF power: r = -0.86, p = 0.024; mean HR: r = 0.89, p = 0.012). Additionally, Social Responsiveness Scale (SRS) raw total scores (mean HR, r = 0.86, p = 0.024) and Aberrant Behavior Checklist (ABC) raw total scores (mean HR r = 0.94, p = 0.017) were correlated with mean heart rate (HR) and HRV-derived parameters. These results provide further evidence of synergy of probiotic and OT combination and help us gain a better understanding of the role of the gut-brain axis in ASD phenotypes and pathogenesis.