# Gut Microbiome and Chlamydia pathogenicity in the upper genital tract

> **NIH NIH R21** · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · 2020 · $186,845

## Abstract

Gut Microbiome and Chlamydia pathogenicity in the upper genital tract
Abstract
Chlamydia trachomatis (CT) can cause long-lasting tubal fibrosis/adhesion/hydrosalpinx/infertility. However,
the mechanism remains unclear. Studies based on C. muridarum (CM) mouse genital tract infection model
have defined chlamydial ascension and tubal inflammation as two key pathogenic determinants. Both
chlamydial and host factors that can affect chlamydial ascension and tubal inflammation have been
identified. However, these factors cannot fully explain chlamydial pathogenicity in some cases. Some mice
with both adequate ascending infection and tubal inflammation still fail to develop significant long-lasting
hydrosalpinx. Clinically, only a fraction of women with high titers of anti-Chlamydia antibodies develop tubal
infertility. Thus, efforts have been made to correlate genital microbiota profiles with susceptibility to
chlamydial infection. However, it remains to determine whether lower genital tract microbiota can impact
chlamydial pathogenicity in the upper genital tract. On the other hand, gut microbiota are associated with
pathogenic fibrosis and can induce profibrotic/regulatory T cells as well as impact extra-GI tissue
pathologies. However, the role of gut microbiome in chlamydial induction of tubal fibrosis has not been
seriously investigated. We recently screened 11 different mouse strains for susceptibility to CM induction of
tubal fibrosis/hydrosalpinx and found that intravaginal inoculation with CM failed to induce significant
hydrosalpinx in DBA/2J mice despite the fact that CM both ascended to the oviduct and induced tubal
inflammation. We took advantage of this surprising finding for evaluating the impact of gut microbiota on
chlamydial pathogenicity. When we used an oral antibiotic cocktail (Abx) consisting of vancomycin and
gentamycin (that cannot penetrate mammalian cell membranes and are unable to affect chlamydial
infection) to induce gut dysbiosis, the DBA/2J mice became highly susceptible to induction of hydrosalpinx
by intravaginal inoculation with CM. Furthermore, the oral Abx-promoted CM pathogenicity correlated with
both gut dysbiosis and increased profibrotic T cell responses but the genital microbiota or chlamydial
infections were not altered by the same oral Abx regime. We hypothesize that the oral Abx regime may
promote chlamydial pathogenicity in the upper genital tract by inducing gut dysbiosis that favors the
development of T cells able to enhance tubal fibrosis. Testing this hypothesis will open up a new dimension
for investigating chlamydial pathogenicity, add a new example to the growing list of mechanisms by which
gut microbiome regulates extra-gut tissue pathology, lay a foundation for in-depth understanding on how gut
microbial species regulate fibrotic responses and finally provide correlates for designing human studies.

## Key facts

- **NIH application ID:** 9864027
- **Project number:** 5R21AI133386-02
- **Recipient organization:** UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
- **Principal Investigator:** GUANGMING ZHONG
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $186,845
- **Award type:** 5
- **Project period:** 2019-02-05 → 2023-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9864027

## Citation

> US National Institutes of Health, RePORTER application 9864027, Gut Microbiome and Chlamydia pathogenicity in the upper genital tract (5R21AI133386-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9864027. Licensed CC0.

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