SYSTEMATIC REVIEW article

Front. Mol. Neurosci.

Sec. Brain Disease Mechanisms

Volume 18 - 2025 | doi: 10.3389/fnmol.2025.1576388

This article is part of the Research TopicRole of Microbiota in Neurocognitive Disorders: A Developmental Origin PerspectiveView all 12 articles

Recognition of the Microbial Metabolite p-Cresol in Autism Spectrum Disorder: Systematic Review and Meta-Analysis

Provisionally accepted
María Isabel Serrano-TomásMaría Isabel Serrano-Tomás1Paulina Contreras-RomeroPaulina Contreras-Romero2Mara ParelladaMara Parellada3Javier ChavesJavier Chaves1Javier ZamoraJavier Zamora1Martha B HengstMartha B Hengst2Patricia PozoPatricia Pozo2Rosa Del CampoRosa Del Campo4*Sheyla GuzmánSheyla Guzmán2
  • 1Ramón y Cajal University Hospital, Madrid, Madrid, Spain
  • 2Catholic University of the North, Antofagasta, Antofagasta, Chile
  • 3Gregorio Marañón Hospital, Madrid, Madrid, Spain
  • 4Ramón y Cajal Institute for Health Research, Madrid, Spain

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In recent years, research has focused on the gut-brain axis and its microbial metabolites as potential etiological or physiopathological agents of autism spectrum disorders (ASDs). Elevated levels of the organic compound para-cresol (p-cresol) have been reported in various populations of children with ASD, suggesting that it could be validated as a possible ASD biomarker related to microbiota. The aim of this study was to perform a systematic review of p-cresol in ASD along with a meta-analysis to elucidate the scientific evidence of its potential as a biomarker. A search was performed in the PubMed and Web of Science databases from inception to May 2024, using Preferred Reporting Items for Systematic Reviews (PRISMA) guidance. The Axis critical appraisal tool was used to evaluate the methodological quality of the studies included in the review.Three independent reviewers examined the identified records and performed data extraction. The systematic review yielded 15 articles, of which only 6 were ultimately used for the meta-analysis. Urinary p-cresol levels were significantly higher in those with ASD than in healthy controls, whereas no significant differences were observed in feces.This meta-analysis validates that in ASD an increased level of p-cresol is detected in urine, which could represent a marker of microbiota evolution assessment in the pathogenesis of the disease. However, further research is needed to determine whether there is a causal relationship between the role of this metabolite and the pathophysiology of ASD.

Keywords: Autism Spectrum Disorder, p-cresol, Metabolites, microbiome, gut-brain axis

Received: 13 Feb 2025; Accepted: 06 Jun 2025.

Copyright: © 2025 Serrano-Tomás, Contreras-Romero, Parellada, Chaves, Zamora, Hengst, Pozo, Del Campo and Guzmán. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Rosa Del Campo, Ramón y Cajal Institute for Health Research, Madrid, Spain

Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

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