Use of the second-generation antipsychotic, risperidone, and secondary weight gain are associated with an altered gut microbiota in children

S M Bahr; B C Tyler; N Wooldridge; B D Butcher; T L Burns; L M Teesch; C L Oltman; M A Azcarate-Peril; J R Kirby; C A Calarge

doi:10.1038/tp.2015.135

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Use of the second-generation antipsychotic, risperidone, and secondary weight gain are associated with an altered gut microbiota in children

Journal article

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Use of the second-generation antipsychotic, risperidone, and secondary weight gain are associated with an altered gut microbiota in children

S M Bahr, B C Tyler, N Wooldridge, B D Butcher, T L Burns, L M Teesch, C L Oltman, M A Azcarate-Peril, J R Kirby and C A Calarge

Translational psychiatry, Vol.5(10), pp.e652-e652

10/06/2015

DOI: 10.1038/tp.2015.135

PMCID: PMC4930121

PMID: 26440540

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Abstract

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.

Adolescent

Antipsychotic Agents - administration & dosage

Antipsychotic Agents - adverse effects

Bacteroidetes - drug effects

Bacteroidetes - isolation & purification

Child

Cross-Sectional Studies

Female

Firmicutes - drug effects

Firmicutes - isolation & purification

Gastrointestinal Microbiome - drug effects

Humans

Male

Mental Disorders - drug therapy

Mental Disorders - microbiology

Risperidone - administration & dosage

Risperidone - adverse effects

Weight Gain - drug effects

Details

Title: Subtitle: Use of the second-generation antipsychotic, risperidone, and secondary weight gain are associated with an altered gut microbiota in children
Creators: S M Bahr - University of Iowa
B C Tyler - University of Iowa
N Wooldridge - University of Iowa
B D Butcher - University of Iowa
T L Burns - University of Iowa
L M Teesch - University of Iowa
C L Oltman - Department of Internal Medicine and Iowa City Veterans Affairs Health Care System, University of Iowa, Iowa City, IA, USA.
M A Azcarate-Peril - University of North Carolina at Chapel Hill
J R Kirby - University of Iowa
C A Calarge - University of Iowa
Resource Type: Journal article
Publication Details: Translational psychiatry, Vol.5(10), pp.e652-e652
DOI: 10.1038/tp.2015.135
PMID: 26440540
PMCID: PMC4930121
NLM abbreviation: Transl Psychiatry
ISSN: 2158-3188
eISSN: 2158-3188
Grant note: 2UL1TR000442-06 / NCATS NIH HHS P30 DK034987 / NIDDK NIH HHS U24 DK100469 / NIDDK NIH HHS K23MH085005 / NIMH NIH HHS
Language: English
Date published: 10/06/2015
Academic Unit: Epidemiology; Core Research Facilities; Fraternal Order of Eagles Diabetes Research Center; Medicine Administration
Record Identifier: 9984363634102771

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