There was a reduction in irritability and anger, improvements in speech characteristics, as well as improved levels of plasma alpha-synuclein (α-synuclein).
α-synuclein has been considered as an important biomarker for the diagnosis of autism and autism spectrum disorder (ASD). Synucleins are small soluble proteins that regulate neurotransmitter release, and its imbalance or mutation in the proteins and receptors were suggested to be linked with ASD.
Some studies have also reported a strong association between lower levels of α-synuclein and ASD.
At present, there is no cure for ASD, and interventions involve speech and behavioural therapies to improve the symptoms.
The significance of the microbiota-gut-brain axis has been observed in a range of gut-related diseases and disorders related to the nervous system, such as Alzheimer’s disease, multiple sclerosis, Parkinson’s disease, and ASD.
So, researchers from India and Japan wanted to study the effects of beta-glucan as a food supplement in children with ASD.
Beta-glucans, when consumed as food supplements have shown to modulate the gut microbiota.
In this study, the Nichi Glucan supplement (black yeast–derived AFO-202 beta-glucan), which is produced by Japan-based GN Corporation, was given to the subjects.
According to one of the authors, Dr Samuel Abraham, who is also the head of R&D at GN Corporation: “Beta glucans have prebiotic properties and prebiotics are known to balance gut dysbiosis.
“Also, constipation is a common problem among children with ASD, and our survey in Japan among customers who regularly consume this product (Nichi Glucan) revealed that close to two-thirds were consuming it as it helps relieve constipation.
“In addition, α-synuclein is lesser in children with ASD compared to their normal age-matched controls, but there has been no report on an intervention or therapy or manoeuvre that could in any manner regulate them yet in the literature to our knowledge.”
According to Abraham, other dietary supplementation have been trialled in ASD patients, mostly vitamins, omega-3, probiotics, and sulforaphane, while studies on beta glucan were mostly conducted in animal models.
“This beta 1,3-1,6 glucan produced as an exopolysaccharide by Black yeast Aureobasidium Pullulans has never been studied before in an ASD population.”
Based on this knowledge, researchers studied the effects of Nichi Glucan in children with ASD, and the outcomes were childhood autism rating scale (CARS) score and α-synuclein levels.
The paper is currently published on the preprint server Medrxiv and awaiting peer-review.
For this pilot clinical trial, 13 subjects were recruited (3 to 18 years old), they were all diagnosed with ASD.
They were split into two arms, group 1 (n=4) was the control and underwent remedial behavioural therapies and 500 mg of L-Carnosine per day.
Group 2 (n=9) underwent supplementation with Nichi Glucan food supplement (0.5g/sachet, twice daily) along with remedial behavioural therapies and 500 mg of L-Carnosine per day.
According to Abraham, L-Carnosine acts as an antioxidant, antitoxic and neuroprotective agent, and its supplementation has been evaluated in clinical studies of children with autism.
The current study lasted 90 days, and childhood autism rating scale (CARS) was monitored at baseline and after three months.
A score below 30 indicates absence of sufficient signs and symptoms, a score between 30 and 36 indicates mild-to-moderately severe autism, and a score from 37 to 60 is related to severe autism.
Blood samples were collected at baseline and at day 90 to study α-synuclein levels.
There was a significant decrease in the CARS score in the Nichi Glucan group compared to the control (p = 0.034517).
There was improvement in the emotional response, including reduction in irritability and anger (88%), sleep improvement (88%), speech characteristics with improvement in finger pointing and monosyllables in 77%, and improved responses to the caregiver in 77% of the children in Nichi Glucan group, but these improvements were very mild in the control group.
Plasma levels of α-synuclein were significantly higher in Nichi Glucan than in the control group (p = 0.091701).
At baseline, mean plasma levels of α-synuclein was around 9.39 ng/dl. After 90 days, this increased to 26.72 ng/dl.
In the control group, mean plasma levels of α-synuclein was about 9.73 ng/dl at baseline, slightly increasing to 10.56 ng/dl after 90 days.
More research needed
Studies on children with ASD have indicated losses of connections or underconnectivity of neurons, leading to behavioural manifestations.
Beta-glucan has been proven to reduce the expression of inflammatory and proinflammatory markers such as Il-6 and TNF-α, which have been shown to be expressed in higher levels in children with autism.
The mechanism in which beta-glucan promoted behavioural improvement and regulated α-synuclein levels need more research, especially on its effects on the gut-microbial ecosystem.
According to Abraham, there were no adverse reactions in any of the subjects, and safety was ensured.
These findings suggest that nutritional supplementation with Nichi Glucan could improve behavioural CARS score, α-synuclein and sleep parameters compared to the control group.
“Although further validations need to be performed, the study confirms the potential of Nichi Glucan as a simple but effective food supplement to be considered as a routine in children with ASD,” researchers wrote.
Based on these results, the firm hopes to “educate paediatricians, especially those who are managing children with ASD. If institutes or companies are interested in a larger multi-centric study for further authentication and gather statistically significant data, we are open for a collaboration,” Abraham said.
As a pilot study, there were limited number of participants, and an unequal distribution of participants between the groups, so larger randomised, multi-centric clinical trials are warranted
“Further research on the mechanisms of its action in improving α-synuclein levels and balancing the immune system in the context of managing chronic inflammation and gut-microbiota regulation as a prebiotic is likely to improve understanding of other diseases caused by neuroinflammation such as Alzheimer’s or Parkinson’s disease.”
Beyond this study on autism, GN Corporation is also developing novel strains of the same species of black yeast which has the potential to address specific conditions centred around the immune system.
It is also in the midst of a COVID-19 pilot study with the same food supplement.
“Improvement of behavioural pattern and alpha-synuclein levels in autism spectrum disorder after consumption of a beta-glucan food supplement in a randomized, parallel-group pilot clinical study”
Authors: Samuel JK Abraham, et al.