Details

Autor(en) / Beteiligte

• Bermudez-Martin, Patricia
• Becker, Jérôme A J
• Caramello, Nicolas
• Fernandez, Sebastian P
• Costa-Campos, Renan
• Canaguier, Juliette
• Barbosa, Susana
• Martinez-Gili, Laura
• Myridakis, Antonis
• Dumas, Marc-Emmanuel
• Bruneau, Aurélia
• Cherbuy, Claire
• Langella, Philippe
• Callebert, Jacques
• Launay, Jean-Marie
• Chabry, Joëlle
• Barik, Jacques
• Le Merrer, Julie
• Glaichenhaus, Nicolas
• Davidovic, Laetitia

Titel

The microbial metabolite p-Cresol induces autistic-like behaviors in mice by remodeling the gut microbiota

Ist Teil von

• Microbiome, 2021-07, Vol.9 (1), p.157-23, Article 157

Ort / Verlag

England: BioMed Central

Erscheinungsjahr

2021

Quelle

2022 ECC(Springer)

Beschreibungen/Notizen

• 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. Our study paves the way for therapeutic interventions targeting the microbiota and p-Cresol production to treat patients with ASD. Video abstract.