Microbiota-driven transcriptional changes in prefrontal cortex override genetic differences in social behavior
Gene-environment interactions impact the development of neuropsychiatric disorders, but the relative contributions are unclear. Here, we identify gut microbiota as sufficient to induce depressive-like behaviors in genetically distinct mouse strains. Daily gavage of saline in non-obese diabetic (NOD) mice induced a social avoidance behavior that was not observed in C57BL/6 mice. This was not observed in NOD animals with depleted microbiota via oral administration of antibiotics. Transfer of intestinal microbiota, including members of the Clostridiales, Lachnospiraceae and Ruminococcaceae, from vehicle-gavaged NOD donors to microbiota-depleted C57BL/6 recipients was sufficient to induce social avoidance and change gene expression and myelination in the prefrontal cortex. Metabolomic analysis identified increased cresol levels in these mice, and exposure of cultured oligodendrocytes to this metabolite prevented myelin gene expression and differentiation. Our results thus demonstrate that the gut microbiota modifies the synthesis of key metabolites affecting gene expression in the prefrontal cortex, thereby modulating social behavior.
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Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All of the animals were handled according to approved institutional animal care and use committee (IACUC) protocols of the Icahn School of Medicine at Mount Sinai (#08-0676, #08-0675; LA10-00398; LA12-00193; LA12-00146).
- Peggy Mason, University of Chicago, United States
- Received: December 3, 2015
- Accepted: April 7, 2016
- Accepted Manuscript published: April 20, 2016 (version 1)
- Accepted Manuscript updated: May 3, 2016 (version 2)
- Version of Record published: May 16, 2016 (version 3)
© 2016, Gacias et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Microbes in the gut influence the social behaviour of mice.
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