Gut Microbiota and Its Role in Autism Spectrum Disorder Progression in Mice

Recent research has uncovered a significant link between gut microbiota and the progression of autism spectrum disorder (ASD) in mice, shedding light on the complex interactions between the gut, immune system, and brain functions. ASD, affecting approximately 1 in 31 children in the US by 2025, shows higher prevalence in East Asian countries like South Korea, Singapore, and Japan. Despite its rise, the precise causes of ASD remain elusive, and current treatments are limited.

A team from POSTECH and ImmunoBiome in Korea, led by Professor Sin-Hyeog Im, has revealed a multifaceted mechanism behind ASD development. Their study, published in Nature Communications, demonstrates that gut microbiota and host immune responses collaboratively influence ASD symptoms in a genetically predisposed mouse model.

While ASD was traditionally viewed as primarily genetic, evidence now points to environmental and microbial factors playing crucial roles. The human gut contains trillions of microbes vital for metabolism and immune development. Studies have shown that individuals with ASD often have distinct gut microbiota compositions, with gastrointestinal disorders present in up to 90% of patients, supporting the gut–brain axis hypothesis that gut microbes can impact brain health and behavior.

In their experiments, the researchers created germ-free (GF) ASD mice—the first such genetically engineered model—allowing analysis of the individual effects of microbiota and genetics. GF-ASD mice lacking gut microbes exhibited fewer ASD-like behaviors and reduced neuroinflammation, especially in reactive microglia and a newly identified brain-resident T cell population. Depleting T cells prevented ASD-like symptoms, highlighting a gut-immune-brain signaling pathway.

Further analysis using 16S-rRNA sequencing and metabolomics revealed that gut microbiota influence the balance between glutamate and GABA, neurotransmitters involved in neural excitation and inhibition. An imbalance in these chemicals can alter neuronal activity and behavioral outcomes in ASD.

To address this, ImmunoBiome's AI team developed a computational model to identify probiotic strains capable of restoring neurotransmitter balance. They identified Limosilactobacillus reuteri IMB015, which can uptake glutamate and produce GABA. Treatment with this probiotic in ASD mice normalized metabolic levels, reduced neuroinflammation, and improved behavioral symptoms.

The company plans to develop L. reuteri IMB015 as a therapeutic probiotic or live biotherapeutic product (LBP), initiating preclinical safety tests and advancing to clinical trials to evaluate its efficacy in humans.

This groundbreaking study not only emphasizes the significance of gut microbiota in ASD but also opens new avenues for microbiome-based therapies that could potentially offer effective management of ASD symptoms in the future.

source: https://medicalxpress.com/news/2025-08-gut-microbiota-linked-autism-spectrum.html