Use of the second-generation antipsychotic, risperidone, and secondary weight gain are associated with an altered gut microbiota in children
Open accessAbstract
The atypical antipsychotic risperidone (RSP) is often associated with weight gain and cardiometabolic side effects. The mechanisms for these adverse events are poorly understood and, undoubtedly, multifactorial in etiology. In light of growing evidence implicating the gut microbiome in the host's energy regulation and in xenobiotic metabolism, we hypothesized that RSP treatment would be associated with changes in the gut microbiome in children and adolescents. Thus, the impact of chronic (>12 months) and short-term use of RSP on the gut microbiome of pediatric psychiatrically ill male participants was examined in a cross-sectional and prospective (up to 10 months) design, respectively. Chronic treatment with RSP was associated with an increase in body mass index (BMI) and a significantly lower ratio of Bacteroidetes:Firmicutes as compared with antipsychotic-naïve psychiatric controls (ratio=0.15 vs 1.24, respectively; P<0.05). Furthermore, a longitudinal observation, beginning shortly after onset of RSP treatment, revealed a gradual decrease in the Bacteroidetes:Firmicutes ratio over the ensuing months of treatment, in association with BMI gain. Lastly, metagenomic analyses were performed based on extrapolation from 16S ribosomal RNA data using the software package, Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt). Those data indicate that gut microbiota dominating the RSP-treated participants are enriched for pathways that have been implicated in weight gain, such as short-chain fatty acid production.
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APs are believed to induce or exacerbate GMB changes.
“Moreover, APs are believed to induce or exacerbate GMB changes106.”
From Autonomic nervous system dysfunction in schizophrenia: impact on cognitive and metabolic health (2021) · cites this paper as [106]
The Discussion reports a shift in gut microbiota following second-generation antipsychotic use, and the Results describe changes appearing after children began risperidone treatment (page numbers unavailable). This supports a possible drug-related change, but the paper does not establish the claim for antipsychotics as a whole or specifically show that they exacerbate pre-existing microbiota changes. (LLM, conf=0.84)
Experimental — accuracy not yet measuredRisperidone 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 Bahr et al., 2015
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Self-citation
- Authors
- Bahr, S. M., Tyler, B. C., Wooldridge, N., Butcher, B. D., Burns, T. L., Teesch, L. M., Oltman, C. L., Azcarate-Peril, M. A., Kirby, J. R., & Calarge, C. A.
- Affiliations
- University of Iowa (US)
- Corresponding author
- Kirby, J R
- Calarge, C A
- Venue
- Translational Psychiatry
- Published
- 2015-10-06
- Volume
- 5
- Issue
- 10
- Pages
- e652-e652
- ISSN
- 2158-3188 (ISSN-L)
- PMC
- PMC4930121
- OpenAlex
- W2226763745
- Cited by
- 197
- References
- 41
- Citations by year
- 2026: 9 · 2025: 10 · 2024: 11 · 2023: 29 · 2022: 17 · 2021: 29 · 2020: 26 · 2019: 25 · 2018: 19 · 2017: 12 · 2016: 8 · 2015: 2
- FWCI
- 5.93
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Translational Psychiatry (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Carolina Digital Repository (University of North Carolina at Chapel Hill) (submittedVersion)
- UNC Libraries
- Funders
- Fraternal Order of Eagles
- National Institutes of Health (UL1TR000442)
- Roy J. and Lucille A. Carver College of Medicine, University of Iowa
- National Institute of Mental Health (K23MH085005)
- National Institute of Diabetes and Digestive and Kidney Diseases (U24DK100469, P30DK034987)
- National Center for Research Resources
- National Center for Advancing Translational Sciences
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Keywords
- risperidone, atypical antipsychotics, gut microbiota, Firmicutes/Bacteroidetes ratio, body mass index, short-chain fatty acids, metagenomics, PICRUSt, children and adolescents
- MeSH terms
- Bacillota, Gastrointestinal Microbiome, Adolescent, Mental Disorders, Child, Cross-Sectional Studies, Female, Humans, Male, Antipsychotic Agents, Weight Gain, Risperidone, Bacteroidetes
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