Microbiome volume 9 , Article number: Cite this article. Metrics details. Autism 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.
Mice 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. The 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.
