# The role of bile acid-microbiome cross-talk in psychotropic-induced weight gain and cardiometabolic dysfunction

> **NIH NIH R21** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2020 · $234,498

## Abstract

Abstract
Weight gain and metabolic dysfunction are common, serious side effects of many psychiatric
medications, especially antipsychotic drugs. These effects are amplified in children and can
severely compromise physical health and interfere with psychiatric treatment. While the
mechanism of antipsychotic-induced weight gain (AIWG) is poorly understood, studies in
rodents have argued for a central role of gut microbes. Our team showed a similar effect in
children taking the antipsychotic risperidone (RSP). We further hypothesized that gut microbes
could impact weight and metabolism by altering bile acid (BA) signaling. Primary BAs made in
the liver are converted to secondary BAs by gut bacteria. These two types of BAs have
opposing effects on the liver farnesoid X receptor (FXR), involved in metabolism and energy
balance. In support of this model, we determined that RSP exposure in youth with autism
resulted in plasma BA elevations. The BA balance was distinct between those who gained
weight on RSP and those who did not. Higher primary BAs favored weight gain, while higher
secondary BAs were protective. This pattern was repeated in a small independent sample of
children taking RSP and interestingly, in children taking selective serotonin reuptake inhibitors
(SSRIs). Therefore, this proposal seeks to test this novel gut microbe-BA model of AIWG in
children started on RSP by their physician for any mental illness. We will follow 60 children
during the first 8 weeks of RSP treatment and collect blood and stool to measure BAs and gut
microbes respectively. In those who gain weight with RSP treatment compared to those who do
not, we predict a decrease in the abundance of gut bacteria capable of converting primary to
secondary BAs and a resultant shift in the BA pool toward primary BAs. If proven, this model
could guide clinical interventions to prevent metabolic side effects, as several potential
treatments impacting this system are currently available for other uses. Additionally, this
mechanism may apply more globally to other drug classes and possibly to obesity and
metabolic dysfunction in general.

## Key facts

- **NIH application ID:** 9856469
- **Project number:** 5R21HD095548-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** ERIKA L NURMI
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $234,498
- **Award type:** 5
- **Project period:** 2019-02-01 → 2023-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9856469

## Citation

> US National Institutes of Health, RePORTER application 9856469, The role of bile acid-microbiome cross-talk in psychotropic-induced weight gain and cardiometabolic dysfunction (5R21HD095548-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9856469. Licensed CC0.

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