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PLoS One. 2014 Dec 15;9(12):e115225. doi: 10.1371/journal.pone.0115225. eCollection 2014.

The antipsychotic olanzapine interacts with the gut microbiome to cause weight gain in mouse.

Author information

1
Departments of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America; Curriculum in Bioinformatics and Computational Biology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.
2
Departments of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.
3
Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.
4
The Jackson Laboratory, Bar Harbor, Maine, United States of America.
5
Department of Biology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America; Curriculum in Bioinformatics and Computational Biology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.
6
Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America; Center for Gastrointestinal Biology and Disease, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.
7
Center for Gastrointestinal Biology and Disease, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.
8
Departments of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America; Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.

Abstract

The second-generation antipsychotic olanzapine is effective in reducing psychotic symptoms but can cause extreme weight gain in human patients. We investigated the role of the gut microbiota in this adverse drug effect using a mouse model. First, we used germ-free C57BL/6J mice to demonstrate that gut bacteria are necessary and sufficient for weight gain caused by oral delivery of olanzapine. Second, we surveyed fecal microbiota before, during, and after treatment and found that olanzapine potentiated a shift towards an "obesogenic" bacterial profile. Finally, we demonstrated that olanzapine has antimicrobial activity in vitro against resident enteric bacterial strains. These results collectively provide strong evidence for a mechanism underlying olanzapine-induced weight gain in mouse and a hypothesis for clinical translation in human patients.

PMID:
25506936
PMCID:
PMC4266663
DOI:
10.1371/journal.pone.0115225
[Indexed for MEDLINE]
Free PMC Article

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