# Uncovering Microbial Modifiers of Antidepressant Responses during Pregnancy

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2023 · $501,675

## Abstract

PROJECT SUMMARY/ABSTRACT
Depression is a prevalent condition that disproportionately afflicts women, including up to 20% of women during
pregnancy. Selective serotonin reuptake inhibitors (SSRIs) used to treat antenatal depression in pregnant
women vary greatly in their efficacy across individuals, and there are concerns that maternal SSRI treatment
detrimentally affects fetal development to elevate risk for adverse obstetric outcomes and neurodevelopmental
abnormalities in the offspring. Research is needed to identify the factors that regulate the efficacy of SSRIs and
that modify maternal-fetal responses to SSRI treatment during pregnancy. Understanding the variables that
regulate the effects of SSRIs is paramount to identifying safer and more efficacious treatments for depression in
pregnant women and to limiting harmful effects of maternal SSRI treatment on developing offspring. The gut
microbiome is emerging as one such factor that interacts directly and indirectly with SSRIs. We recently
discovered that SSRI treatment during pregnancy alters the composition of the maternal gut microbiome, and
that depletion of the maternal gut microbiome modifies fetal brain responses to maternal SSRI treatment. We
further determined that the SSRI-associated gut bacterium Turicibacter sanguinis binds SSRIs through a
previously uncharacterized protein orthologue of the mammalian serotonin transporter. This evidence raises the
important question of how the gut microbiome impacts maternal and fetal responses to SSRI treatment for
antenatal depression. To address this, we will define the impact of SSRI treatment on the function of the maternal
gut microbiome in pregnant mice, in pregnant women, and in the SSRI-binding bacterium T. sanguinis (Aim 1).
We will further test the hypothesis that variations in the maternal gut microbiome modify the pharmacokinetics
of SSRI absorption and distribution across the maternal-fetal interface (Aim 2). Finally, we will determine effects
of the maternal gut microbiome on the efficacy of SSRI treatment against symptoms of antenatal depression
(Aim 3). We will additionally assess how the maternal gut microbiome impacts the detrimental effects of maternal
SSRI treatment on neurodevelopment and behavior of the offspring. Findings from our study will reveal
fundamental mechanisms for microbial interactions with SSRIs, with the potential to transform interventional
strategies for treating symptoms of antenatal depression, while limiting adverse consequences of SSRIs on
developing offspring.

## Key facts

- **NIH application ID:** 10600387
- **Project number:** 1R01HD111079-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Elaine Hsiao
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $501,675
- **Award type:** 1
- **Project period:** 2023-09-01 → 2028-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10600387

## Citation

> US National Institutes of Health, RePORTER application 10600387, Uncovering Microbial Modifiers of Antidepressant Responses during Pregnancy (1R01HD111079-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10600387. Licensed CC0.

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