# Host-Microbiota Interactions and Chlamydia Trachomatis Infection Outcomes

> **NIH NIH R21** · UNIVERSITY OF MARYLAND BALTIMORE · 2021 · $240,021

## Abstract

PROJECT SUMMARY
The risk of sexually transmitted infection (STI) in humans depends on multiple biological factors, among which
the occurrence of a cervicovaginal microbiota that is `permissive' to STI stands out. The microbial composition
of a STI-permissive microbiota is similar to that observed in association with the syndrome of bacterial vaginosis,
a condition that is generally defined by a high pH (>4.5), the absence of Lactobacillus spp. and an array of strict
and facultative anaerobes such as Gardnerella vaginalis, Atopobium vaginae, Megasphaera spp., and Prevotella
spp. In contrast, a typical `non-permissive' microbiota is dominated by one of several species of Lactobacillus, a
unique feature of the human cervicovaginal microbiota. The mechanism(s) by which a non-permissive
cervicovaginal microbiota provides protection against STIs remains poorly understood, as no animal or cell
culture model system developed to date satisfactorily reproduces the cervicovaginal mucosa in its natural
environment as a target for experimental infection. As a consequence, our knowledge of the pathogenesis of
STIs is incomplete, particularly as it pertains to the critical role of the human cervicovaginal microbiota. We have
established extensive preliminary data that support the scientific premise of this project and states that a non-
permissive indigenous microbiota interacts with the cervicovaginal epithelium to establish a homeostatic state
that blocks STI and/or reduces disease severity. Conversely, a permissive microbiota disrupts host cell
homeostasis, thereby allowing STI to progress. Advanced 3D organotypic models of the cervicovaginal mucosa
that eliminate the inherent ethical and biological limitations of existing models will be used to test this hypothesis,
using the most prevalent agent of STIs worldwide, Chlamydia trachomatis. We aim to develop a better
understanding of the host-microbiota interactions and how they modulate the fate of C. trachomatis infection. In
this project, 3D organotypic models colonized with different types of reconstructed microbiota will be exploited
to ask specific questions about how different types of microbiota (permissive and non-permissive) modulate
epithelial cell functioning (Aim 1) in relationship to their susceptibility/resistance to chlamydial infection (Aim 2).
We will also assess the preclinical potential of the model for testing preventive (Aim 2) and therapeutic (Aim 3)
interventions against STIs. For these studies, we will leverage the full force of state-of-the-art microscopic and
RNA-sequencing methodologies to identify and characterize microbiota specific alterations of structural and host
epithelial homeostasis and expand our understanding of the triangular relationship between the host, the
microbiota and C. trachomatis.

## Key facts

- **NIH application ID:** 10239625
- **Project number:** 1R21AI162006-01
- **Recipient organization:** UNIVERSITY OF MARYLAND BALTIMORE
- **Principal Investigator:** LARRY J FORNEY
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $240,021
- **Award type:** 1
- **Project period:** 2021-07-12 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10239625

## Citation

> US National Institutes of Health, RePORTER application 10239625, Host-Microbiota Interactions and Chlamydia Trachomatis Infection Outcomes (1R21AI162006-01). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10239625. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*