# Vaginal microbiota transplant to promote Lactobacillus-dominant cervicovaginal communities

> **NIH NIH R01** · MASSACHUSETTS GENERAL HOSPITAL · 2024 · $832,912

## Abstract

PROJECT SUMMARY
Vaginal colonization with a Lactobacillus-dominant microbial community is associated with lower risk for preterm
birth, HIV acquisition, HPV persistence and cervical dysplasia. A diverse, Lactobacillus-deficient vaginal
microbiota such as that seen in bacterial vaginosis (BV) is associated with mucosal inflammation, which is likely
the mechanistic link to the adverse health outcomes seen with dysbiosis. Antibiotic treatment for BV achieves
short term cure, but recurrence is common. Probiotic treatment to restore healthy lactobacilli is only moderately
successful, even with daily treatment. These results emphasize the need for novel strategies to manipulate the
genital microbiome and produce sustainable shifts away from dysbiosis. We propose a randomized clinical
trial of vaginal microbiota transplant (VMT) with extensive characterization of donors, transplant material,
recipients and engraftment, to identify determinants of vaginal microbial colonization and stability. Our team has
already obtained an IND, successfully recruited donors, and generated preliminary data demonstrating stability
of Lactobacillus in donated material. In Aim 1 we will enroll up to 25 healthy donors and 126 recipients with a
history of recurrent BV and an abnormal Nugent score. Recipients receive 1 week of oral metronidazole and are
randomized to VMT or saline placebo, two doses given on non-consecutive days in a single week. The primary
outcome is prevalence of a Lactobacillus-dominant vaginal microbiota by 16S rRNA sequencing 1 month after
intervention. Secondary outcomes include adverse events, Lactobacillus dominance over the entire 6 month
follow up, and prevalence of BV by Nugent score at 1, 3 & 6 months. In Aim 2 we will characterize the impact of
vaginal fluid transplantation on recipient microbiome (Aim 2.1) and mucosal inflammation (Aim 2.2). For Aim 2.1
we will use 16S rRNA sequencing, qPCR and shotgun metagenomic sequencing (SMS) to define the kinetics of
Lactobacillus colonization and community diversity over the 6 months following study intervention. In Aim 2.2 we
will assess the impact of VMT vs. placebo on soluble markers of inflammation in vaginal fluid and endocervical
immune cell activation. In Aim 3 we will identify genetic characteristics of both successful donations and
Lactobacillus isolates cultivated from successful VMT donors and recipients (Aim 3.1). We will compare isolates
in vitro to test functional metrics for future selection of strains for novel products (Aim 3.2). We will also compare
metabolic profiles of successful vs. unsuccessful donations (Aim 3.3). The resulting isolate collection and
database of genes and metabolites associated with achieving Lactobacillus dominance will provide a basis for
design of a novel live biotherapeutic for prevention of BV and its associated sequelae. Execution of these three
aims will also provide novel insights into determinants of vaginal Lactobacillus colonization and the causal
relati...

## Key facts

- **NIH application ID:** 10686205
- **Project number:** 5R01AI158836-03
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Caroline M Mitchell
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $832,912
- **Award type:** 5
- **Project period:** 2021-09-20 → 2027-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10686205

## Citation

> US National Institutes of Health, RePORTER application 10686205, Vaginal microbiota transplant to promote Lactobacillus-dominant cervicovaginal communities (5R01AI158836-03). Retrieved via AI Analytics 2026-06-10 from https://api.ai-analytics.org/grant/nih/10686205. Licensed CC0.

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