The role of microbial-derived p-Cresol in autism spectrum disorder: A systematic review of the gut–brain axis

IF 2.6 Q3 NUTRITION & DIETETICS

Clinical nutrition ESPEN Pub Date : 2025-08-07 DOI:10.1016/j.clnesp.2025.08.010

Desirée Victoria-Montesinos, Ana María García-Muñoz, María Teresa Mercader-Ros, Carmen Lucas-Abellán, Mónica González-Monjarás, Pablo Barcina-Pérez

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引用次数: 0

Abstract

Background & aims

Autism Spectrum Disorder (ASD) is a complex neurodevelopmental condition increasingly associated with gut microbiota alterations. Among microbial metabolites, p-Cresol has emerged as a potential contributor to the pathophysiology of ASD. This systematic review aims to examine the evidence linking p-Cresol and its metabolites with ASD and explore their potential role within the gut–brain axis framework, a bidirectional communication system where gut microbiota influence brain function via immune, metabolic, and neural pathways (e.g., vagus nerve, microbial metabolites).

Methods

A comprehensive literature search was conducted in PubMed, Web of Science, Scopus, and Cochrane up to March 2025, following PRISMA 2020 guidelines. Studies were included if they quantified p-Cresol or its derivatives in biological samples from individuals with ASD. Data extraction and risk of bias assessment were performed independently by two reviewers. The protocol was prospectively registered in PROSPERO (CRD420251007080).

Results

Seventeen studies met the inclusion criteria. Most reported elevated urinary or fecal p-Cresol levels in individuals with ASD compared to controls, with consistent associations found between p-Cresol concentrations and (1); gastrointestinal symptoms, particularly constipation and diarrhea; (2) specific microbiota alterations including increased Clostridium difficile and Desulfovibrio abundance; and (3) behavioral manifestations and ASD severity. However, heterogeneity in study designs, small sample sizes, and variability in analytical techniques limit the generalizability of the results.

Conclusion

p-Cresol and its microbial precursors may contribute to ASD pathophysiology through gut–brain axis interactions. Although current evidence supports this association, further longitudinal and mechanistic studies are needed to confirm causality and evaluate p-Cresol as a biomarker or therapeutic target in ASD.

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微生物衍生的对甲酚在自闭症谱系障碍中的作用：肠-脑轴的系统回顾。

背景与目的：自闭症谱系障碍（ASD）是一种复杂的神经发育疾病，与肠道微生物群的改变越来越相关。在微生物代谢物中，对甲酚已成为ASD病理生理的潜在贡献者。本系统综述旨在研究对甲酚及其代谢物与ASD相关的证据，并探讨其在肠-脑轴框架中的潜在作用，肠-脑轴框架是肠道微生物群通过免疫、代谢和神经通路（如迷走神经、微生物代谢物）影响大脑功能的双向通信系统。方法：根据PRISMA 2020指南，在PubMed， Web of Science， Scopus和Cochrane中进行了截至2025年3月的综合文献检索。如果研究对ASD患者生物样本中的对甲酚或其衍生物进行量化，则纳入研究。数据提取和偏倚风险评估由两名审稿人独立完成。该方案在PROSPERO （CRD420251007080）前瞻性注册。结果：17项研究符合纳入标准。与对照组相比，大多数ASD患者尿液或粪便中对甲酚水平升高，对甲酚浓度与(1)之间存在一致的关联；胃肠道症状，特别是便秘和腹泻；(2)特定微生物群的改变，包括艰难梭菌和脱硫弧菌的丰度增加；(3)行为表现和ASD严重程度。然而，研究设计的异质性、小样本量和分析技术的可变性限制了结果的普遍性。结论：对甲酚及其微生物前体可能通过肠-脑轴相互作用参与ASD的病理生理。虽然目前的证据支持这种关联，但需要进一步的纵向和机制研究来确认因果关系，并评估对甲酚作为ASD的生物标志物或治疗靶点。

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来源期刊

Clinical nutrition ESPEN NUTRITION & DIETETICS-

CiteScore

4.90

自引率

3.30%

发文量

512

期刊介绍： Clinical Nutrition ESPEN is an electronic-only journal and is an official publication of the European Society for Clinical Nutrition and Metabolism (ESPEN). Nutrition and nutritional care have gained wide clinical and scientific interest during the past decades. The increasing knowledge of metabolic disturbances and nutritional assessment in chronic and acute diseases has stimulated rapid advances in design, development and clinical application of nutritional support. The aims of ESPEN are to encourage the rapid diffusion of knowledge and its application in the field of clinical nutrition and metabolism. Published bimonthly, Clinical Nutrition ESPEN focuses on publishing articles on the relationship between nutrition and disease in the setting of basic science and clinical practice. Clinical Nutrition ESPEN is available to all members of ESPEN and to all subscribers of Clinical Nutrition.