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Updated: Apr 19, 2026
Analysis of Fecal Microbiota Dynamics in Lupus-Prone Mice Using a Simple, Cost-Effective DNA Isolation Method
Published on: May 2, 2022
The antipsychotic olanzapine interacts with the gut microbiome to cause weight gain in mouse
Andrew P Morgan1, James J Crowley2, Randal J Nonneman2
1Departments 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.
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.
Insights
Gut bacteria drive olanzapine-induced weight gain. Researchers found that the antipsychotic drug olanzapine alters gut microbes, promoting an "obesogenic" profile and leading to significant weight gain in mice.
Area of Science:
- Microbiology
- Pharmacology
- Gastroenterology
Background:
- Second-generation antipsychotics like olanzapine effectively manage psychotic symptoms.
- A significant adverse effect of olanzapine is extreme weight gain in patients.
- The role of the gut microbiota in olanzapine-induced weight gain remains unclear.
Purpose of the Study:
- To investigate the necessity and sufficiency of gut microbiota in olanzapine-induced weight gain.
- To characterize the changes in gut microbiota composition during olanzapine treatment.
- To explore the antimicrobial effects of olanzapine on enteric bacteria.
Main Methods:
- Utilized germ-free C57BL/6J mice to assess the role of gut bacteria.
- Analyzed fecal microbiota composition before, during, and after olanzapine administration.
- Performed in vitro antimicrobial assays against resident enteric bacterial strains.
Main Results:
- Gut bacteria were demonstrated to be both necessary and sufficient for olanzapine-induced weight gain.
- Olanzapine treatment induced a shift in gut microbiota towards an "obesogenic" profile.
- Olanzapine exhibited antimicrobial activity against specific enteric bacterial strains in vitro.
Conclusions:
- Gut microbiota play a critical role in the mechanism of olanzapine-induced weight gain.
- The findings provide a potential mechanism for olanzapine's side effect in mice.
- This study offers a hypothesis for clinical translation in human patients regarding olanzapine and weight gain.
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