title: Use of the second-generation antipsychotic, risperidone, and secondary weight gain are associated with an altered gut microbiota in children.
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.
authors.affiliation: Department of Microbiology, University of Iowa, Iowa City, IA, USA.
authors.forename: S M
authors.initials: SM
authors.lastname: Bahr
authors.affiliation: Department of Psychiatry, University of Iowa, Iowa City, IA, USA.
authors.forename: B C
authors.initials: BC
authors.lastname: Tyler
authors.affiliation: Department of Psychiatry, University of Iowa, Iowa City, IA, USA.
authors.forename: N
authors.initials: N
authors.lastname: Wooldridge
authors.affiliation: Department of Psychiatry, University of Iowa, Iowa City, IA, USA.
authors.forename: B D
authors.initials: BD
authors.lastname: Butcher
authors.affiliation: Department of Epidemiology, University of Iowa, Iowa City, IA, USA.
authors.forename: T L
authors.initials: TL
authors.lastname: Burns
authors.affiliation: High Resolution Mass Spectrometry Facility, University of Iowa, Iowa City, IA, USA.
authors.forename: L M
authors.initials: LM
authors.lastname: Teesch
authors.affiliation: Department of Internal Medicine and Iowa City Veterans Affairs Health Care System, University of Iowa, Iowa City, IA, USA.
authors.forename: C L
authors.initials: CL
authors.lastname: Oltman
authors.affiliation: Department of Cell Biology and Physiology and Microbiome Core Facility, University of North Carolina, Chapel Hill, NC, USA.
authors.forename: M A
authors.initials: MA
authors.lastname: Azcarate-Peril
authors.affiliation: Department of Microbiology, University of Iowa, Iowa City, IA, USA.
authors.forename: J R
authors.initials: JR
authors.lastname: Kirby
authors.affiliation: Department of Psychiatry, University of Iowa, Iowa City, IA, USA.|Baylor College of Medicine, The Menninger Department of Psychiatry and Behavioral Sciences, Texas Children's Hospital, Houston, TX, USA.
authors.forename: C A
authors.initials: CA
authors.lastname: Calarge
mesh_terms: D000293:Adolescent; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000009:adverse effects; D041963:Bacteroidetes / Q000187:drug effects / Q000302:isolation & purification; D002648:Child; D003430:Cross-Sectional Studies; D005260:Female; D000068536:Bacillota / Q000187:drug effects / Q000302:isolation & purification; D000069196:Gastrointestinal Microbiome / Q000187:drug effects*; D006801:Humans; D008297:Male; D001523:Mental Disorders / Q000188:drug therapy / Q000382:microbiology; D018967:Risperidone / Q000008:administration & dosage / Q000009:adverse effects; D015430:Weight Gain / Q000187:drug effects*
chemical_list: D014150:Antipsychotic Agents; D018967:Risperidone