Risperidone-induced weight gain is mediated through shifts in the gut microbiome and suppression of energy expenditure
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Risperidone is a second-generation antipsychotic that causes weight gain. We hypothesized that risperidone-induced shifts in the gut microbiome are mechanistically involved in its metabolic consequences. Wild-type female C57BL/6J mice treated with risperidone (80 μg/day) exhibited significant excess weight gain, due to reduced energy expenditure, which correlated with an altered gut microbiome. Fecal transplant from risperidone-treated mice caused a 16% reduction in total resting metabolic rate in naïve recipients, attributable to suppression of non-aerobic metabolism. Risperidone inhibited growth of cultured fecal bacteria grown anaerobically more than those grown aerobically. Finally, transplant of the fecal phage fraction from risperidone-treated mice was sufficient to cause excess weight gain in naïve recipients, again through reduced energy expenditure. Collectively, these data highlight a major role for the gut microbiome in weight gain following chronic use of risperidone, and specifically implicates the modulation of non-aerobic resting metabolism in this mechanism.
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Risperidone causes shifts in gut microbiome composition in mice and in children and adolescents.
“Another antipsychotic, risperidone, also causes shifts in gut microbiome composition in mice (Bahra et al., 2015), and in children and adolescents (Bahr et al., 2015).”
From Gut reactions: Breaking down xenobiotic–microbiome interactions (2019) · cites this paper as Bahra et al., 2015
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- Authors
- Bahr, S. M., Weidemann, B. J., Castro, A. N., Walsh, J. W., deLeon, O., Burnett, C. M. L., Pearson, N. A., Murry, D. J., Grobe, J. L., & Kirby, J. R.
- Affiliations
- University of Iowa (US)
- Corresponding author
- Kirby, John R.
- ORCID
- Venue
- EBioMedicine
- Publisher
- Elsevier BV
- Published
- 2015-11
- Volume
- 2
- Issue
- 11
- Pages
- 1725-1734
- ISSN
- 2352-3964 (ISSN-L)
- PMC
- PMC4740326
- OpenAlex
- W1781074272
- Cited by
- 143
- References
- 54
- Citations by year
- 2026: 12 · 2025: 12 · 2024: 11 · 2023: 16 · 2022: 14 · 2021: 16 · 2020: 15 · 2019: 17 · 2018: 10 · 2017: 17 · 2016: 2 · 2015: 1
- FWCI
- 4.34
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- EBioMedicine (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Science Foundation (1244021)
- American Diabetes Association (1-14-BS-079)
- Alfred P. Sloan Foundation
- American Heart Association (HL084207, 15SFRN23730000)
- National Institutes of Health (HL098276, HL-084207)
- National Heart, Lung, and Blood Institute (HL098276, HL-084207, P01HL084207, R00HL098276)
- National Institute of Allergy and Infectious Diseases (R01AI108255)
- National Institute of Diabetes and Digestive and Kidney Diseases (U24DK100469)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Keywords
- risperidone, antipsychotic-induced weight gain, gut microbiota, energy expenditure, resting metabolic rate, fecal microbiota transplantation, bacteriophages, anaerobic metabolism, atypical antipsychotics, metabolic side effects
- MeSH terms
- Gastrointestinal Microbiome, Fecal Microbiota Transplantation, Animals, Energy Metabolism, Female, Antipsychotic Agents, Xenobiotics, Weight Gain, Risperidone, Mice, Metagenome, Metagenomics
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