Microbial metabolite p-cresol associates with constipation in adults with high-functioning autism spectrum disorder and induces constipation-like symptoms in mice
Abstract
Gastrointestinal (GI) symptoms are prevalent in Autism Spectrum Disorder (ASD), yet their biological correlates remain poorly understood, notably in adults. The microbiota-derived metabolite p- cresol is reported to be elevated in the urine and stool of ASD patients, but its link to specific GI symptoms in adult high-functioning adults remains unexplored. We examined the relationship between serum levels of p- cresol and its conjugates ( p -cresol sulfate, p -cresol glucuronide) with five common GI symptoms (diarrhea, constipation, abnormal stool aspect, bloating, abdominal pain) in 272 adults with high-functioning ASD (mean age: 30.9 ± 10.3 years; 33.1% females). Clinical and dietary assessments were performed and circulating serum levels of p- cresol and its conjugates were measured using targeted metabolomics in a subsample of 177 patients. Serum levels were specifically measured to capture systemic exposure, in contrast to fecal or urinary levels, which primarily reflect luminal microbiota production or renal excretory capacity of microbial metabolites and their conjugates. Females with ASD had higher rates of GI symptoms and elevated p- cresol levels compared to males. Multivariable regression analysis showed that serum p -cresol, but not its conjugates, was selectively associated with constipation frequency, independent of sex, age, and diet. No associations were observed with the other GI symptoms. In mice, chronic exposure to p -cresol (50 mg/kg/day for 4 weeks) via drinking water to mimic GI exposure to microbial metabolites produced in the intestinal lumen, induced constipation-like GI dysfunction, supporting a causal link. These findings identify p -cresol as a possible mediator of constipation. This work supports the development of tailored interventions for GI symptoms in adults with ASD.
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BibTeX
@article{kraimi2026microbial,
title = {{Microbial metabolite p-cresol associates with constipation in adults with high-functioning autism spectrum disorder and induces constipation-like symptoms in mice}},
author = {Narjis Kraimi and David Fabregat-Safont and Juliette Canaguier and Geoffroy Mallaret and Susana Barbosa and Julie Brouillet and Florian Lejuste and Alexandru Gaman and Jean-Romain Richard and Chema Sahnoun Derbel and Anouck Amestoy and Marion Leboyer and Oscar Pozo and Laetitia Davidovic},
journal = {Scientific Reports},
year = {2026},
month = aug,
doi = {10.1038/s41598-026-62588-y},
url = {https://hal.science/hal-05827271v1},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Microbial metabolite p-cresol associates with constipation in adults with high-functioning autism spectrum disorder and induces constipation-like symptoms in mice
AU - Narjis Kraimi
AU - David Fabregat-Safont
AU - Juliette Canaguier
AU - Geoffroy Mallaret
AU - Susana Barbosa
AU - Julie Brouillet
AU - Florian Lejuste
AU - Alexandru Gaman
AU - Jean-Romain Richard
AU - Chema Sahnoun Derbel
AU - Anouck Amestoy
AU - Marion Leboyer
AU - Oscar Pozo
AU - Laetitia Davidovic
PY - 2026
DA - 2026/08/28
JO - Scientific Reports
DO - 10.1038/s41598-026-62588-y
UR - https://hal.science/hal-05827271v1
AB - Gastrointestinal (GI) symptoms are prevalent in Autism Spectrum Disorder (ASD), yet their biological correlates remain poorly understood, notably in adults. The microbiota-derived metabolite p- cresol is reported to be elevated in the urine and stool of ASD patients, but its link to specific GI symptoms in adult high-functioning adults remains unexplored. We examined the relationship between serum levels of p- cresol and its conjugates ( p -cresol sulfate, p -cresol glucuronide) with five common GI symptoms (diarrhea, constipation, abnormal stool aspect, bloating, abdominal pain) in 272 adults with high-functioning ASD (mean age: 30.9 ± 10.3 years; 33.1% females). Clinical and dietary assessments were performed and circulating serum levels of p- cresol and its conjugates were measured using targeted metabolomics in a subsample of 177 patients. Serum levels were specifically measured to capture systemic exposure, in contrast to fecal or urinary levels, which primarily reflect luminal microbiota production or renal excretory capacity of microbial metabolites and their conjugates. Females with ASD had higher rates of GI symptoms and elevated p- cresol levels compared to males. Multivariable regression analysis showed that serum p -cresol, but not its conjugates, was selectively associated with constipation frequency, independent of sex, age, and diet. No associations were observed with the other GI symptoms. In mice, chronic exposure to p -cresol (50 mg/kg/day for 4 weeks) via drinking water to mimic GI exposure to microbial metabolites produced in the intestinal lumen, induced constipation-like GI dysfunction, supporting a causal link. These findings identify p -cresol as a possible mediator of constipation. This work supports the development of tailored interventions for GI symptoms in adults with ASD.
SN - 2045-2322
ER -