Exploring the neurotoxic effects of microbial metabolites: A potential link between p-Cresol and autism spectrum disorders?

Abstract

Autism spectrum disorder (ASD) is a neurodevelopmental disorder with a complex etiology, including genetic and environmental factors. A growing body of evidence (preclinical and clinical studies) implicates a potential role of gut microbiome dysregulation in ASD pathophysiology. This review focuses on the microbial metabolite p-Cresol, produced by certain gut bacteria such as Clostridium, and its potential role in ASD. The review summarizes studies investigating the gut microbiome composition in ASD patients, particularly the increased abundance of Clostridium species and associated gastrointestinal symptoms. The potential neurotoxic effects of p-Cresol are explored, including its influence on neurotransmitter metabolism (especially dopamine), neuroinflammation, and brain development. The mechanistic findings from the preclinical studies of p-Cresol’s induction of ASD-like behaviors and its impact on the dopaminergic system are discussed. Literature studies indicated increased levels of p-Cresol in the urine of patients with ASD. This increasing evidence suggests that p-Cresol may serve as a crucial biomarker for understanding the relationship between gut microbiota and ASD, opening avenues for potential diagnostic and therapeutic interventions.