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Modulating autism spectrum disorder pathophysiology using a trace amine-focused approach: targeting the gut.

L Pretorius¹, J A Coetzee¹, A P Dos Santos¹

¹Experimental Medicine Group, Dept Medicine, Stellenbosch University, Parow, South Africa.

Molecular Medicine (Cambridge, Mass.)

|May 20, 2025

Summary

Autism spectrum disorder (ASD) is linked to gut-brain axis issues. Targeting the trace amine system, rather than just gut microbes, may offer new therapeutic approaches for ASD symptom management.

Keywords:

Agmatine Behaviour Gut health Gut-brain Polyamine TAAR Tryptamine Tyramine β-PEA

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Area of Science:

Neuroscience
Gastroenterology
Pharmacology

Background:

Autism spectrum disorder (ASD) affects 1% of the population, with significant indirect impact on families.
ASD is associated with high rates of anxiety and gastrointestinal problems.
Current ASD treatments focus on neurological symptoms, often worsening gut health and the gut-brain axis.

Purpose of the Study:

To review trace amine dysregulation in ASD.
To hypothesize how targeting the trace amine system can address ASD symptomology.
To assess current therapeutics development and identify future priorities.

Main Methods:

Literature review of trace amine dysregulation in ASD.
Hypothesis formulation on trace amine system's role in ASD pathophysiology.
Critical assessment of drug development and repurposing strategies.

Main Results:

Trace amines, synthesized in the brain and microbiome, show dysregulation in ASD.
Trace aminergic signaling is crucial for regulatory system homeostasis.
Focusing on functional trace amine signaling dysbiosis, not just microbial composition, is proposed for therapeutics.

Conclusions:

Targeting the trace amine system offers a novel therapeutic avenue for ASD.
A holistic approach considering factors like receptor binding and enzymes is needed.
Future medicine development should prioritize understanding and modulating trace aminergic signaling in ASD.