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.

The microbiome, immunity, and schizophrenia and bipolar disorder

“…Of particular importance would be the interaction of immune related risk genes such as those involved in the complement system (Xiao et al, 2016) with the composition of the microbiome. Animal models would also be useful to better define the effects of psychiatric medications on the composition of the microbiome in terms of both psychiatric activity and side effects such as weigh gain (Bahr et al, 2015). …”

Gut microbiota, metabolism and psychopathology: A critical review and novel perspectives

“…At baseline, when the fecal samples were collected, all but two patients were treated with antipsychotics. To what extent this may have impacted the findings is unclear, but antipsychotics have been found to influence microbiota composition [69][70][71].…”

“…In disorders such as AN, MDD, and ASD, the effect of the disease on diet and GI physiology will certainly control the microbiome and influence the cause or effect question. Along the same lines, use of medication may influence the microbiome composition [69,70] and should be taken into account when analyzing data from studies in which the subjects were not drug naïve. Another challenge pertains to whether observed alterations in gut microbiota are unique to specific types of psychiatric disorders.…”

The Bacteria Among Us

“…By sequencing the 16S ribosomal RNA genewhich provides a genetic fingerprint of microbial identityin both risperdone-treated and untreated individuals, Bahr and Kirby and their colleagues were able to determine that children exposed to long-term antipsychotic treatment exhibit alterations in gut microbial communities. Specifically, the ratio of Bacteroidetes to Firmicutes in the gut drops with extended drug treatment, a change that correlates with weight gain (2). …”