Original ResearchBasic and Translational—Alimentary TractThe Intestinal Microbiota Affect Central Levels of Brain-Derived Neurotropic Factor and Behavior in Mice
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Animals
Male BALB/c mice (8–10 weeks old) were purchased from Harlan (Indianapolis, IN) and maintained under specific pathogen–free (SPF) conditions. Germ-free NIH Swiss and BALB/c mice (7–9 weeks old), obtained from the Farncombe Gnotobiotic Unit of McMaster University, were colonized by gavaging fresh cecal contents from SPF BALB/C and NIH Swiss donors (obtained from the Central Animal Facility of McMaster University). They were housed in ultraclean conditions using ventilated racks. All mice were
Antimicrobial Treatment Induces Changes in the Gut Microbiota
To test whether altering the established intestinal microbiota alters mouse behavior, we administered a mixture of nonabsorbable ATMs or sterile water for 7 days to BALB/c SPF mice. A combination of culture and molecular-based approaches were used to identify changes in the intestinal microbiota. Because many bacteria cannot be cultured, 16S ribosomal RNA targeted polymerase chain reaction–DGGE and sequencing was used to examine microbiota composition. Before treatment, DGGE profiles were
Discussion
The results of this study provide strong evidence for a microbiota–gut–brain axis that influences brain biochemistry and modulates behavior in adult mice. This is supported by several lines of evidence. First, transient perturbation of the microbiota increased hippocampal BDNF and exploratory behavior. Second, these changes were reversible upon normalization of the microbiota after withdrawal of the ATM. Third, ATM administration did not alter behavior in germ-free mice. Fourth, we showed that
Acknowledgments
The authors are grateful to Mr Paul Malinowski for technical assistance.
P.B. and E.D. contributed equally to this manuscript.
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Conflicts of interest These authors disclose the following: S. M. Collins, P. Bercik, and E. F. Verdu received grant support from Nestle Switzerland. The remaining authors disclose no conflicts.
Funding Supported by Canadian Institutes for Health Research and Crohn's and Colitis Foundation of Canada grants (S.M.C., P.B.); E. F. Verdu and Premysl Bercik hold Internal Career Research Awards from the Department of Medicine at McMaster University.