Differences in the Genital Microbiota in Women Who Naturally Clear Chlamydia trachomatis Infection Compared to Women Who Do Not Clear; A Pilot Study

Abstract

In vitro studies indicate IFNγ is central to Chlamydia trachomatis (Ct) eradication, but its function may be compromised by anaerobes typically associated with bacterial vaginosis (BV), a frequent co-morbidity in women with Ct. Here we investigated the associations between natural clearance of cervical Ct infection, the vaginal microbiome, and the requirements for IFNγ by evaluating the vaginal microbial and cytokine composition of Ct treatment visit samples from women who cleared Ct infection in the interim between their Ct screening and Ct treatment visit. The pilot cohort was young, predominantly African American, and characterized by a high rate of BV that was treated with metronidazole at the Ct screening visit. The rate of natural Ct clearance was 23.6% by the Ct treatment visit (median 9 days). 16S rRNA gene sequencing revealed that metronidazole-treated women who had a Lactobacillus spp.-dominant vaginal microbiota (CST 2 or 3) at the Ct treatment visit, were more prevalent in the Ct clearing population than the non-clearing population (86% v. 50%). L. iners (CST2) was the major Lactobacillus spp. present in Ct clearers, and 33% still remained anaerobe-dominant (CST1). Vaginal IFNγ levels were not significantly different in Ct clearers and non-clearers and were several logs lower than that required for killing Ct in vitro. An expanded panel of IFNγ-induced and proinflammatory cytokines and chemokines also did not reveal differences between Ct clearers and non-clearers, but, rather, suggested signatures better associated with specific CSTs. Taken together, these findings suggest that BV-associated bacteria may impede Ct clearance, but a Lactobacillus spp.-dominant microbiome is not an absolute requirement to clear. Further, IFNγ may be required at lower concentrations than in vitro modeling indicates, suggesting it may act together with other factors in vivo. Data also revealed that the vaginal bacteria-driven inflammation add complexity to the genital cytokine milieu, but changes in this microbiota may contribute to, or provide cytokine biomarkers, for a shift to Ct clearance.

Differential Effect of Vaginal Microbiota on Spontaneous Preterm Birth among Chinese Pregnant Women

“…The alpha diversity metrics, including (i) ASV richness, (ii) the Shannon index, (iii) Faith's phylogenetic diversity, and (iv) Pielou's evenness, and beta diversity metrics including (i) the Bray-Curtis dissimilarity, (ii) weighted UniFrac, (iii) unweighted UniFrac, and (iv) the Jaccard distance were detected using the QIIME 2 diversity plugin. The CSTs of vaginal microbiota were clustered based on a Bray-Curtis distance matrix by Partitioning Around Medoids algorithm [ 40 ]. The 175 MetaCyc pathways, which had (i) no less than 5% of inferred abundance for at least one individual and (ii) no less than 15% of pregnant women without zero data, were retained.…”

Human genital antibody-mediated inhibition of Chlamydia trachomatis infection and evidence for ompA genotype-specific neutralization

“…This study utilized IgG and IgA purified from cervicovaginal lavage (CVL) and serum samples from a cohort of fifty-seven women who were recently diagnosed with genital Ct infection by a standard nucleic acid amplification test (NAAT) (Hologic® APTIMA®) and were returning to the clinic for antibiotic treatment. The cohort was young (median age of 24 years), predominantly African American (77%) and 51% had a history of Ct, as described in previous studies [ 33 , 40 ].…”

“…The study was approved by the Louisiana State University Health Sciences Center—New Orleans Institutional Review Board and written consent was obtained from each patient. Detailed demographics of this cohort have been reported previously, and concentrations of total and EB-specific IgG and IgA in serum and genital secretions for the first twelve patients of this cohort have been published previously [ 33 , 40 ]. Informed consent was obtained from each patient.…”

“…Serum, vaginal and endocervical secretions, and 5 ml of cervicovaginal lavage (CVL) were collected as previously described [ 33 ]. Chlamydia trachomatis , Neisseria gonorrhoeae , and Trichomonas vaginalis were detected by the APTIMA® Combo 2 test, bacterial vaginosis by Amsel and Nugent scoring, and viable Ct cervical burden was determined by semi-quantitative culture for inclusion forming units (IFU; median of 878,596 IFU per swab) [ 40 , 42 ].…”

Preterm Prelabor Rupture of Membranes Linked to Vaginal Bacteriome of Pregnant Females in the Early Second Trimester: a Case-Cohort Design

“…The alpha diversity metrics, including (i) ASV richness, (ii) the Shannon index, (iii) Faith’s phylogenetic diversity, and (iv) Pielou’s evenness, and the beta diversity metrics, including (i) Bray–Curtis dissimilarity, (ii) Jaccard distance, (iii) weighted UniFrac, and (iv) unweighted UniFrac were detected using the QIIME 2 diversity plugin. The CSTs of vaginal bacteriome were clustered based on a Bray–Curtis distance matrix by the partitioning around medoids algorithm [ 47 ]. Finally, CST I-IV was derived based on the gap statistic.…”