Impact of Standard Bacterial Vaginosis Treatment on the Genital Microbiota, Immune Milieu, and Ex Vivo Human Immunodeficiency Virus Susceptibility

Joag, Vineet; Obila, Onyango; Gajer, Pawel; Scott, Milcah C.; Dizzell, Sara; Humphrys, Michael S.; Shahabi, Kamnoosh; Huibner, Sanja; Shannon, Brett; Tharao, Wangari; Mureithi, Marianne; Oyugi, Julius; Kimani, Joshua; Kaushic, Charu; Ravel, Jacques; Anzala, Omu; Kaul, Rupert

doi:10.1093/cid/ciy762

Cited by 60 publications

(71 citation statements)

References 40 publications

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“…Interestingly, two patients without metronidazole treatment also changed from BV to CST-III. Such an increase in L. iners following treatment with metronidazole has also been seen in other studies [32,33]. Jacobsson and Forsum suggested that L. iners dominance could be a transitional stage between abnormal and normal microbiota [34].…”

Section: Plos Onesupporting

confidence: 76%

Changes in the vaginal microbiota following antibiotic treatment for Mycoplasma genitalium, Chlamydia trachomatis and bacterial vaginosis

et al. 2020

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The human vagina harbor a rich microbiota. The optimal state is dominated by lactobacilli that help to maintain health and prevent various diseases. However, the microbiota may rapidly change to a polymicrobial state that has been linked to a number of diseases. In the present study, the temporal changes of the vaginal microbiota in patients treated for sexually transmitted diseases or bacterial vaginosis (BV) and in untreated controls were studied for 26 days. The patients included 52 women treated with azithromycin, tetracyclines or moxifloxacin for present or suspected infection with Chlamydia trachomatis or Mycoplasma genitalium. Women with concurrent BV were also treated with metronidazole. The controls were 10 healthy women of matching age. The microbiota was analyzed by 16S rRNA gene deep sequencing, specific qPCRs and microscopy. There was generally good correlation between Nugent score and community state type (CST) and qPCR confirmed the sequencing results. By sequencing, more than 600 different taxa were found, but only 33 constituted more than 1 ‰ of the sequences. In both patients and controls the microbiota could be divided into three different community state types, CST-I, CST-III and CST-IV. Without metronidazole, the microbiota remained relatively stable regarding CST although changes were seen during menstrual periods. Administration of metronidazole changed the microbiota from CST-IV to CST-III in approximately 50% of the treated patients. In contrast, the CST was generally unaffected by azithromycin or tetracyclines. In 30% of the BV patients, Gardnerella vaginalis was not eradicated by metronidazole. The majority of women colonized with Ureaplasma parvum remained positive after azithromycin while U. urealyticum was eradicated.

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Section: Plos Onesupporting

confidence: 76%

Changes in the vaginal microbiota following antibiotic treatment for Mycoplasma genitalium, Chlamydia trachomatis and bacterial vaginosis

et al. 2020

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“…Several studies have characterized CD8+ T-cells in barrier tissues 21 – 23 , 35 , 47 , yet there remains a gap in knowledge on those residing in the CVT, which is a biologically relevant tissue site given that it is the portal of entry for numerous pathogens of global health importance. Moreover, inflammation at this site, due to pathogen infection or to alterations within the commensal flora, has been shown to be associated with increased risk of further infections 28 , 29 . While mounting evidence support a lead role for resident memory T-cells in inflammation in other tissues 48 , little is known about T-cells within the human CVT, and in particular those that do not express the putative Trm markers CD69 and/or CD103.…”

Section: Discussionmentioning

confidence: 99%

“…Interestingly, there is epidemiological evidence indicating that infection with one pathogen is associated with an increased risk of acquiring subsequent infections, as described for HSV-2 and HIV-1 25 – 27 . Further, it has been proposed that inflammation in the CVT, due to pathogens or to dysbiosis of the resident flora, can facilitate subsequent viral infections 28 , 29 . In addition, high levels of genital tract inflammation have been correlated to higher HIV set point and shedding 30 , 31 .…”

Section: Introductionmentioning

confidence: 99%

A pro-inflammatory CD8+ T-cell subset patrols the cervicovaginal tract

et al. 2019

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The immune system of the cervicovaginal tract (CVT) must balance immunosurveillance and active immunity against pathogens with maintenance of tolerance to resident microbiota and to fetal and partner antigens for reproductive purposes. Thus, we predicted that CVT immunity is characterized by distinctive features compared to blood and other tissue compartments. Indeed, we found that CVT CD8+ T-cells had unique transcriptional profiles, particularly in their cytokine signature, compared to that reported for CD8+ T-cells in other tissue sites. Among these CVT CD8+ T-cells, we identified a CD69- CD103- subset that was characterized by reduced migration in response to tissue-exit signals and higher pro-inflammatory potential as compared to their blood counterpart. These inflammatory mucosal CD8+ T-cells (Tim) were increased in frequency in the CVT of individuals with chronic infection, pointing to a potential role in perpetuating inflammation. Our findings highlight the specialized nature of immunity within the CVT and identify Tim cells as potential therapeutic targets to tame tissue inflammation upon chronic infection.

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“…IL-1β is produced as an inactive precursor by multiple cell types and functions to activate CD4+ T cells and generate proinflammatory cytokines 24. Numerous studies have shown an association between BV and IL-1β, and treatment of BV decreases levels of IL-1β 1 25. This analysis demonstrates that detection of several individual bacterial taxa ( D. micraerophilus, Eggerthella sp type 1 , M. hominis or Parvimonas sp type 2) is associated with higher IL-1β concentrations, and that a principal component that comprised highly correlated bacterial taxa was also associated with higher IL-1β concentrations after adjustment for potential confounders.…”

Section: Discussionmentioning

confidence: 66%

Associations between vaginal bacteria implicated in HIV acquisition risk and proinflammatory cytokines and chemokines

Sabo

Lehman²,

Wang

et al. 2019

Sex Transm Infect

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ObjectivesRecent studies have identified vaginal bacterial taxa associated with increased HIV risk. A possible mechanism to explain these results is that individual taxa differentially promote cervicovaginal inflammation. This study aimed to explore relationships between concentrations of bacteria previously linked to HIV acquisition and vaginal concentrations of proinflammatory cytokines and chemokines.MethodsIn this cross-sectional analysis, concentrations of 17 bacterial taxa and four proinflammatory cytokines (interleukin (IL)-1β, IL-6, IL-10 and tumour necrosis factor alpha (TNFα)) and two proinflammatory chemokines (IL-8 and interferon gamma-induced protein 10) were measured in vaginal swabs collected from 80 HIV-uninfected women. Cytokine and chemokine concentrations were compared between women with bacterial concentrations above or below the lower limit of detection as determined by quantitative PCR for each taxon. Principal component analysis was used to create a summary score for closely correlated bacteria, and linear regression analysis was used to evaluate associations between this score and increasing concentrations of TNFα and IL-1β.ResultsDetection of Dialister micraerophilus (p=0.01), Eggerthella sp type 1 (p=0.05) or Mycoplasma hominis (p=0.03) was associated with higher TNFα concentrations, and detection of D. micraerophilus (p<0.01), Eggerthella sp type 1 (p=0.04), M. hominis (p=0.02) or Parvimonas sp type 2 (p=0.05) was associated with significantly higher IL-1β concentrations. Seven bacterial taxa (D. micraerophilus, Eggerthella sp type 1, Gemella asaccharolytica, Sneathia sp, Megasphaera sp, M. hominis and Parvimonas sp type 2) were found to be highly correlated by principal component analysis (eigenvalue 5.24, explaining 74.92% of variability). Linear regression analysis demonstrated associations between this principal component and concentrations of TNFα (β=0.55, 95% CI 0.01 to 1.08; p=0.048) and IL-1β (β=0.96, 95% CI 0.19 to 1.74; p=0.016).ConclusionsThis study provides evidence that several highly correlated vaginal bacterial taxa may influence vaginal cytokine and chemokine concentrations. These results suggest a mechanism where the presence of specific bacterial taxa could influence HIV susceptibility by increasing vaginal inflammation.

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Impact of Standard Bacterial Vaginosis Treatment on the Genital Microbiota, Immune Milieu, and Ex Vivo Human Immunodeficiency Virus Susceptibility

Cited by 60 publications

References 40 publications

Changes in the vaginal microbiota following antibiotic treatment for Mycoplasma genitalium, Chlamydia trachomatis and bacterial vaginosis

Changes in the vaginal microbiota following antibiotic treatment for Mycoplasma genitalium, Chlamydia trachomatis and bacterial vaginosis

A pro-inflammatory CD8+ T-cell subset patrols the cervicovaginal tract

Associations between vaginal bacteria implicated in HIV acquisition risk and proinflammatory cytokines and chemokines

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