BUGS AND WORMS AND OTHER GREAT STUFF
As my regular readers know, I love to report the results of double-blinded, randomized, placebo controlled trials in human to you: they represent bringing us a major step forward toward better treatments for, well, everything. Today’s paper is on a subject near and dear to my heart: autism: my son Alex was diagnosed 25 years ago, and for a quarter of a century I have stayed abreast of biomedical research in the field. This one is super interesting.
We’ve known for many years now that those on the autism spectrum have alterations in their microbiomes, and those alterations are now accepted to be a likely cause – or at least one of the causes – of the developmental disorder. Thus, probiotics have been studied in the population, as has fecal microbiota transplant, with some good degree of success. (There are many posts on The Biome Buzz: for just two examples, see here and here.). “Gut microbiome composition and inflammation have been reported to be involved in the pathogenesis of ASD through the gut–brain axis. Recent evidence demonstrates that alterations in the gut microbiota of ASD individuals changes both gastrointestinal (GI) physiology and behaviors via the gut–microbiome–brain axis. Probiotic varieties used in both animal studies and clinical trials have demonstrated efficacy in improving ASD core symptoms.”[i]
Another treatment that has proven somewhat useful in ameliorating some of the social difficulties some on the spectrum have is the hormone oxytocin, which plays a huge role in bonding mother to baby, as well as being associated with empathy, trust, relationship-building, and more. It is produced in the hypothalamus, and as this paper says, it is “… well known for its ability to modulate emotional and social communication, bonding, and reward-related behaviors.” It is believed that oxytocin is producible by probiotic bacteria, such as Lactobacillus reuteri, which I have actually mentioned in relationship to favorable outcomes in autism in previous posts. So, while both have shown some efficacy, no one has ever tested them both being used together.
This was a stage two pilot trial of 35 individuals with ASD, aged 2-20 years. They were randomly assigned to receive daily 60 billion units (so a sizeable dose) of Lactobacillus plantarum PS128 probiotic or a placebo for 28 weeks. Starting on week 16, both groups received oxytocin. Outcomes were measured by multiple assessments: primary outcomes were socio-behavioral severity and aberrant behaviors. Secondary outcomes also included fecal microbiome analysis, blood levels of inflammatory markers and oxytocin levels. The two groups were compared at baseline, 16 weeks and 28 weeks.
The results were striking: in those receiving both treatments, statistically significant improvements were seen in socio-behavioral severity and aberrant behaviors in comparison to those only receiving the probiotic. Significant improvement was also seen in the gut microbiome and interestingly, they were even able to isolate the bacterial species that seemed most correlated with these improvements: “The favorable social cognition response of the combination regimen is highly correlated with the abundance of the Eubacterium hallii group.”
Of course, this was a small trial of only 35 individuals – a much larger trial is warranted, certainly. After all, the authors conclude that the combination of this probiotic and intranasal oxytocin “…in participants with ASD may reduce ASD core socio-behavioral symptoms and clinical global functioning. Statistically significant improvements in ASD-related outcomes over the treatment course via combined therapy are attributed to the proposed synergistic interactions between the two treatments, which are mediated via the gut–brain axis. Furthermore, participants receiving combined therapy showed significant improvements in gut.” Seeing as there have been precious few advances in autism treatment in the 25 years+ since Alex was diagnosed, I am always glad to see something new, different, low risk and promising.
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[i] Kong XJ, Liu J, Liu K, Koh M, Sherman H, Liu S, Tian R, Sukijthamapan P, Wang J, Fong M, Xu L, Clairmont C, Jeong MS, Li A, Lopes M, Hagan V, Dutton T, Chan SP, Lee H, Kendall A, Kwong K, Song Y. Probiotic and Oxytocin Combination Therapy in Patients with Autism Spectrum Disorder: A Randomized, Double-Blinded, Placebo-Controlled Pilot Trial. Nutrients. 2021 May 5;13(5):1552. doi: 10.3390/nu13051552. PMID: 34062986; PMCID: PMC8147925.