Imperial College London
Alternate

DrLauraMartinez Gili

Faculty of Medicine, Department of Metabolism, Digestion and Reproduction

Research Fellow
 
 
 
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Contact

 

l.martinez-gili Website

 
 
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Location

 

Queen Elizabeth the Queen Mother Wing (QEQM)St Mary's Campus

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Summary

 

Publications

Citation

BibTex format

@article{Bermudez-Martin:2021:10.1186/s40168-021-01103-z,
author = {Bermudez-Martin, P and Becker, JAJ and Caramello, N and Fernandez, SP and Costa-Campos, R and Canaguier, J and Barbosa, S and Martinez-Gili, L and Myridakis, A and Dumas, M-E and Bruneau, A and Cherbuy, C and Langella, P and Callebert, J and Launay, J-M and Chabry, J and Barik, J and Le, Merrer J and Glaichenhaus, N and Davidovic, L},
doi = {10.1186/s40168-021-01103-z},
journal = {Microbiome},
pages = {1--23},
title = {The microbial metabolite p-Cresol induces autistic-like behaviors in mice by remodeling the gut microbiota},
url = {http://dx.doi.org/10.1186/s40168-021-01103-z},
volume = {9},
year = {2021}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - 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.
AU  - Bermudez-Martin,P
AU  - Becker,JAJ
AU  - Caramello,N
AU  - Fernandez,SP
AU  - Costa-Campos,R
AU  - Canaguier,J
AU  - Barbosa,S
AU  - Martinez-Gili,L
AU  - Myridakis,A
AU  - Dumas,M-E
AU  - Bruneau,A
AU  - Cherbuy,C
AU  - Langella,P
AU  - Callebert,J
AU  - Launay,J-M
AU  - Chabry,J
AU  - Barik,J
AU  - Le,Merrer J
AU  - Glaichenhaus,N
AU  - Davidovic,L
DO  - 10.1186/s40168-021-01103-z
EP  - 23
PY  - 2021///
SN  - 2049-2618
SP  - 1
TI  - The microbial metabolite p-Cresol induces autistic-like behaviors in mice by remodeling the gut microbiota
T2  - Microbiome
UR  - http://dx.doi.org/10.1186/s40168-021-01103-z
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000672464200001&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - https://microbiomejournal.biomedcentral.com/articles/10.1186/s40168-021-01103-z
UR  - http://hdl.handle.net/10044/1/91482
VL  - 9
ER  -
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