ArticleMicrobiome2021
The microbial metabolite p-Cresol induces autistic-like behaviors in mice by remodeling the gut microbiota.
Article in Microbiome, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 99 papers, 2 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
99 citing papers in PubMed, 2 syntheses or guidelines pooled it, 147 citations in OpenAlex.
- p-Cresol and p-Cresyl Sulphate Boost Oxidative Stress: A Systematic Review of Recent Evidence.Basic & clinical pharmacology & toxicology · 2025Pooled it
- Recognition of the microbial metaboliteFrontiers in molecular neuroscience · 2025Pooled it
- Altered Gut Microbiota and Short-chain Fatty Acids in Chinese Children with Constipated Autism Spectrum Disorder.Scientific reports · 2023Trial
- Safety and target engagement of an oral small-molecule sequestrant in adolescents with autism spectrum disorder: an open-label phase 1b/2a trial.Nature medicine · 2022Trial
- Integrated multi-omics analysis identifies microbial and metabolic signatures and drivers of CNS autoimmunity.mSystems · 2026Article
- Research Progress on Bidirectional Regulation of the Microbiota-Gut-Brain Axis in Autism Spectrum Disorder Based on the Immune-Metabolic-Endocrine Interactive Network.Biomolecules · 2026Review
- Elevated microbially-derived metabolites in autism: a possible diagnostic screening test for a distinct ASD phenotype.Molecular psychiatry · 2026Article
- Gut microbiota-derived 5-HTP penetrates the host blood-brain barrier and ameliorates autism symptoms.Acta pharmaceutica Sinica. B · 2026Article
- Non-invasive Vagal Nerve Stimulation as a Potential Treatment for Repetitive Blast Trauma.bioRxiv : the preprint server for biology · 2026Article
- Microbiome biomarkers in autism spectrum disorder: Toward prediction, diagnosis, and prognosis.Cell reports. Medicine · 2026Review
- Enterococcus hirae QT4713-derived dopamine ameliorates intestinal inflammation and MPTP-induced Parkinson's disease in mice.NPJ Parkinson's disease · 2026Article
- Unveiling the Molecular Mechanism of Intestinal Metabolite para-Cresol in Modulating Neuroinflammation and Synaptic Dysfunction: Implications for Autism Spectrum Disorder.Journal of neurochemistry · 2026Article
- Integrated Metagenomic and Metabolomic Profiling Identifies Predictive Biomarkers for Overweight Status in a Mongolian Population.Microorganisms · 2026Article
- S'Wipe: user-friendly stool collection for high-throughput gut metabolomics and multi-omics.mSystems · 2026Article
- Early risperidone exposure impairs cognitive function by perturbation of the gut microbiome and bile acids/tyrosine-PTP1B axis.Microbiome · 2026Article
- Article
- Computational Identification of Blood-Brain Barrier-Permeant Microbiome Metabolites with Binding Affinity to Neurotransmitter Receptors in Neurodevelopmental Disorders.Molecules (Basel, Switzerland) · 2026Article
- Integrated multi-omics analysis identifies microbial and metabolic signatures and drivers of CNS autoimmunity.bioRxiv : the preprint server for biology · 2026Article
- The oral-amplifier hypothesis: linking oral inflammation to intestinal microbial activity in autism spectrum disorder.Frontiers in microbiology · 2026Article
- The Vitamin D-Gut-Brain Axis in Autism Spectrum Disorder: A Bidirectional Crosstalk.International journal of general medicine · 2026Review
39 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
20 authors at 7 institutions in 3 countries.
Funding
Abstract
backgroundAutism spectrum disorders (ASD) are associated with dysregulation of the microbiota-gut-brain axis, changes in microbiota composition as well as in the fecal, serum, and urine levels of microbial metabolites. Yet a causal relationship between dysregulation of the microbiota-gut-brain axis and ASD remains to be demonstrated. Here, we hypothesized that the microbial metabolite p-Cresol, which is more abundant in ASD patients compared to neurotypical individuals, could induce ASD-like behavior in mice.
resultsMice exposed to p-Cresol for 4 weeks in drinking water presented social behavior deficits, stereotypies, and perseverative behaviors, but no changes in anxiety, locomotion, or cognition. Abnormal social behavior induced by p-Cresol was associated with decreased activity of central dopamine neurons involved in the social reward circuit. Further, p-Cresol induced changes in microbiota composition and social behavior deficits could be transferred from p-Cresol-treated mice to control mice by fecal microbiota transplantation (FMT). We also showed that mice transplanted with the microbiota of p-Cresol-treated mice exhibited increased fecal p-Cresol excretion, compared to mice transplanted with the microbiota of control mice. In addition, we identified possible p-Cresol bacterial producers. Lastly, the microbiota of control mice rescued social interactions, dopamine neurons excitability, and fecal p-Cresol levels when transplanted to p-Cresol-treated mice.
conclusionsThe microbial metabolite p-Cresol induces selectively ASD core behavioral symptoms in mice. Social behavior deficits induced by p-Cresol are dependant on changes in microbiota composition. Our study paves the way for therapeutic interventions targeting the microbiota and p-Cresol production to treat patients with ASD. Video abstract.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.