Format

Send to

Choose Destination
Elife. 2016 Apr 20;5. pii: e13442. doi: 10.7554/eLife.13442.

Microbiota-driven transcriptional changes in prefrontal cortex override genetic differences in social behavior.

Author information

1
Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, United States.
2
Icahn Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, United States.
3
Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, United States.
4
BERG, Framingham, United States.
5
Department of Anatomy and Neurobiology, Virginia Commonwealth University, Richmond, United States.
6
Department of Pharmacology and Systems Therapeutics, Icahn School of Medicine at Mount Sinai, New York, United States.
7
Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, United States.

Abstract

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 vehicle (dH2O) in nonobese 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.

KEYWORDS:

behavior; brain; gut; microbiome; mouse; myelin; neuroscience; psychiatry

PMID:
27097105
PMCID:
PMC4880443
DOI:
10.7554/eLife.13442
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for eLife Sciences Publications, Ltd Icon for PubMed Central
Loading ...
Support Center