Probiotic therapy potential? New research uncovers gut-immune-brain pathway in autism

New research argues that the gut microbiota, rather than genetics, may be the main cause of autism spectrum disorder (ASD). It reveals that the host immune system also impacts the progression of the condition in a genetic mouse model.

The study in Nature Communications warns that ASD impacts one in 31 children in the US by 2025. However, its prevalence in East Asian countries like South Korea, Singapore, and Japan may be even higher. 

Researchers from ImmunoBiome and Pohang University of Science & Technology, Korea, add that the condition’s cause is poorly understood. No cures or preventative measures are available. 

However, based on the discovery of mechanisms behind ASD, ImmunoBiome’s AI team is advancing the potential of probiotics to rebalance metabolic imbalances.

Although ASD is largely believed to be genetically driven, growing evidence points to bacterial and environmental factors. The researchers highlight that microbes impact metabolism and the development of the immune system. The human gut contains more than ten times more microbial cells than human cells.

ASD mechanisms across gut, immune & brain

The study found a multifaceted mechanism behind ASD after researchers created the “world’s first germ-free genetic mouse model.” This enabled them to study the effects of genetics, gut microbiota, metabolites, and immune response on ASD progression. 

ImmunoBiome plans to advance L. reuteri IMB015 as a live biotherapeutic product or probiotic for ASD treatment.The germ-free ASD mice, lacking gut microbiota, showed reduced ASD-linked behaviors. The researchers posit that this shows the gut microbiota, rather than genetics, could be the dominant driver of ASD symptoms.

These mice also showed reduced neuroinflammation, especially in newly discovered inflammatory microglia and the brain-resident T cell population.

Researchers prevented ASD-like phenotypes by depleting T cells, showing a gut-immune-brain signaling pathway in ASD.

In detail, a different glutamate/GABA ratio may directly impact ASD neuronal activity and behavior. The gut microbiota was found to influence the balance between these neurotransmitters.

Probiotics and biotherapeutics for ASD

ImmunoBiome’s AI team created an in silico model to predict probiotic strains with metabolic functions. This was used to address the glutamate/GABA ratio imbalance.

It found that Limosilactobacillus reuteri IMB015 could uptake glutamate and produce GABA. According to the researchers, treating ASD mouse models with this probiotic strain restored metabolic balance, reduced neuroinflammation, and changed behavioral abnormalities. 

The company says it plans to advance L. reuteri IMB015 as a live biotherapeutic product or probiotic for ASD treatment. It will carry out a thorough preclinical toxicity evaluation and progress to clinical trials in humans.

In May, research found that newborn babies with vitamin D deficiency are at greater risk of developing attention deficit/hyperactivity disorder (ADHD), ASD, and schizophrenia. It suggested that mothers supplementing vitamin D during pregnancy could reduce these risks.

According to a joint metagenomics study last year, personalized synbiotics may alleviate symptoms of ASD by addressing the gut-brain axis. Additionally, a clinical study combining a synbiotic from dsm-firmenich with gut-directed hypnotherapy significantly reduced gastrointestinal discomfort, irritability, and anxiety symptoms in children with autism.