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Risperidone-induced weight gain is mediated through shifts in the gut microbiome and suppression of energy expenditure
Open accessAbstract
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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“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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Metadata
- 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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