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

Sarah M. Bahr, Benjamin J. Weidemann, Ana N. Castro, John W. Walsh, Orlando deLeon, Colin M.L. Burnett, Nicole A. Pearson, Daryl J. Murry, Justin L. Grobe, John R. Kirby

Research output: Contribution to journalArticlepeer-review

64 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)1725-1734
Number of pages10
Issue number11
StatePublished - Nov 1 2015
Externally publishedYes


  • Fecal transfer
  • Non-aerobic resting metabolic rate
  • Phage transfer
  • Risperidone induced weight gain

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)


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