A NEW study has revealed significant links between gut-derived metabolites and brain activity related to autism spectrum disorder (ASD), providing fresh insight into the complex relationship between the gut and the brain. Researchers focused on how metabolites from dietary tryptophan – a key amino acid – may influence brain function and ASD symptomatology.
The gut microbiome is known to produce nearly 40% of all circulating metabolites, many of which affect brain processes. Within the brain-gut-microbiome (BGM) system, these molecules can travel via the bloodstream or nerve pathways such as the vagus nerve, which transmits a vast amount of sensory information from the gut to the brain. This communication network is believed to impact behaviour, emotional regulation, and sensory responses.
In individuals with ASD, early-life gut dysbiosis – or imbalance in gut microbiota – has been linked to changes in brain structure and function. This study found that levels of tryptophan-related fecal metabolites, particularly those in the kynurenine pathway, differed significantly between autistic and neurotypical participants. Lower levels of kynurenate (a neuroprotective compound) and higher kynurenine/kynurenate ratios were observed, both of which may contribute to neurotoxic effects during brain development.
The research also found that these metabolite levels were linked to brain activity in regions associated with social and emotional processing, including the insula and mid-cingulate cortex. For example, reduced levels of indole metabolites — produced solely by gut bacteria — were correlated with more severe autism symptoms and atypical disgust responses.
Importantly, brain activity in certain areas was shown to mediate the relationship between gut metabolites and behavioural symptoms, supporting the idea of a mechanistic connection. Though the study is cross-sectional and cannot confirm causality, it marks a critical step toward understanding how gut microbes might influence neurodevelopmental disorders such as ASD.
Future studies are needed to explore these findings further, ideally using longitudinal and interventional approaches, to assess whether targeting gut microbiota could offer therapeutic benefits for autism.
Reference
Aziz-Zadeh L et al. Relationships between brain activity, tryptophan-related gut metabolites, and autism symptomatology. Nat Commun. 2025;16(1):3465.
