title: The antipsychotic olanzapine interacts with the gut microbiome to cause weight gain in mouse.
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.
authors.affiliation: 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.
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Morgan
authors.affiliation: Departments of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.
authors.forename: James J
authors.initials: JJ
authors.lastname: Crowley
authors.affiliation: Departments of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.
authors.forename: Randal J
authors.initials: RJ
authors.lastname: Nonneman
authors.affiliation: Departments of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.
authors.forename: Corey R
authors.initials: CR
authors.lastname: Quackenbush
authors.affiliation: Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.
authors.forename: Cheryl N
authors.initials: CN
authors.lastname: Miller
authors.affiliation: Departments of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.
authors.forename: Allison K
authors.initials: AK
authors.lastname: Ryan
authors.affiliation: The Jackson Laboratory, Bar Harbor, Maine, United States of America.
authors.forename: Molly A
authors.initials: MA
authors.lastname: Bogue
authors.affiliation: 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.
authors.forename: Sur Herrera
authors.initials: SH
authors.lastname: Paredes
authors.affiliation: 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.
authors.forename: Scott
authors.initials: S
authors.lastname: Yourstone
authors.affiliation: 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.
authors.forename: Ian M
authors.initials: IM
authors.lastname: Carroll
authors.affiliation: Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Kawula
authors.affiliation: Center for Gastrointestinal Biology and Disease, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.
authors.forename: Maureen A
authors.initials: MA
authors.lastname: Bower
authors.affiliation: 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.
authors.forename: R Balfour
authors.initials: RB
authors.lastname: Sartor
authors.affiliation: 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.
authors.forename: Patrick F
authors.initials: PF
authors.lastname: Sullivan
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000633:toxicity*; D001569:Benzodiazepines / Q000633:toxicity*; D005260:Female; D000069196:Gastrointestinal Microbiome / Q000187:drug effects*; D051379:Mice; D000077152:Olanzapine; D015430:Weight Gain / Q000187:drug effects*
chemical_list: D014150:Antipsychotic Agents; D001569:Benzodiazepines; D000077152:Olanzapine