Microbiome Composition and Function Drives Wound-Healing Impairment in the Female Genital Tract

Zevin, Alexander S.; Xie, Irene Y.; Birse, Kenzie; Arnold, Kelly B.; Romas, Laura; Westmacott, Garrett; Novak, Richard M.; McCorrister, Stuart; McKinnon, Lyle R.; Cohen, Craig R.; Mackelprang, Romel D.; Lingappa, Jairam R.; Lauffenburger, D. A.; Klatt, Nichole R.; Burgener, Adam

doi:10.1371/journal.ppat.1005889

Cited by 113 publications

(132 citation statements)

References 42 publications

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“…This TFV metabolism can happen quite rapidly and research has shown reduced tenofovir-diphosphate (TFV-DP, the active form of TFV) levels in cervical tissue within two hours and depleted TFV concentrations in cervicovaginal fluid and plasma after one week when high concentrations of Gardnerella vaginalis are present (13 ■■ ,33 ■■ ). CAPRISA-004 participants with non- Lactobacillus dominant microbiota also had enhanced cellular membrane transport protein expression, which could have provided another mechanism for rapid TFV metabolism in cervicovaginal tissue for individuals using gel-based PrEP (34 ■■ ). …”

Section: Text Of Reviewmentioning

confidence: 99%

The Vaginal Microbiome and its Potential to Impact Efficacy of HIV Pre-exposure Prophylaxis for Women

Velloza

Heffron

2017

Curr HIV/AIDS Rep

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Purpose of review This review describes existing evidence addressing the potential modulation of PrEP products, specifically 1% tenofovir (TFV) gel and oral tenofovir-based PrEP, by vaginal dysbiosis and discusses future considerations for delivering novel, long-acting PrEP products to women at high-risk for vaginal dysbiosis and HIV. Recent findings We describe results from analyses investigating the modification of PrEP efficacy by vaginal dysbiosis and studies of biological mechanisms that could render PrEP ineffective in the presence of specific microbiota. A secondary analysis from the CAPRISA-004 cohort demonstrated that there is no effect of the 1% TFV gel in the presence of non-Lactobacillus dominant microbiota. Another recent analysis comparing oral tenofovir-based PrEP efficacy among women with and without bacterial vaginosis in the Partners PrEP Study found that oral PrEP efficacy is not modified by bacterial vaginosis. Gardnerella vaginalis, commonly present in women with vaginal dysbiosis, can rapidly metabolize TFV particularly when it is locally applied and thereby prevent TFV integration into cells. Given that vaginal dysbiosis appears to modulate efficacy for 1% TFV gel but not for oral tenofovir-based PrEP, vaginal dysbiosis is potentially less consequential to HIV protection from TFV in the context of systemic drug delivery and high product adherence. Summary Vaginal dysbiosis may undermine the efficacy of 1% TFV gel to protect women from HIV but not the efficacy of oral PrEP. Ongoing development of novel ring, injectable, and film-based PrEP products should investigate whether vaginal dysbiosis can reduce efficacy of these products, even in the presence of high adherence.

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Section: Text Of Reviewmentioning

confidence: 99%

The Vaginal Microbiome and its Potential to Impact Efficacy of HIV Pre-exposure Prophylaxis for Women

Velloza

Heffron

2017

Curr HIV/AIDS Rep

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“… further showed that suppression of inflammation prior to SIV inoculation prevented SIV infection. In addition to recruiting target cells to the site of transmission, there is evidence showing that pro‐inflammatory cytokines facilitate HIV transmission by reducing the integrity of the epithelial barrier in the female genital tract and directly promoting HIV replication through NF‐kB activation .…”

Section: Introductionmentioning

confidence: 99%

The genital tract and rectal microbiomes: their role in HIV susceptibility and prevention in women

et al. 2019

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Introduction Young women in sub‐Saharan Africa are disproportionately affected by HIV, accounting for 25% of all new infections in 2017. Several behavioural and biological factors are known to impact a young woman's vulnerability for acquiring HIV. One key, but lesser understood, biological factor impacting vulnerability is the vaginal microbiome. This review describes the vaginal microbiome and examines its alterations, its influence on HIV acquisition as well as the efficacy of HIV prevention technologies, the role of the rectal microbiome in HIV acquisition, advances in technologies to study the microbiome and some future research directions. Discussion Although the composition of each woman's vaginal microbiome is unique, a microbiome dominated by Lactobacillus species is generally associated with a “healthy” vagina. Disturbances in the vaginal microbiota, characterized by a shift from a low‐diversity, Lactobacillus ‐dominant state to a high‐diversity non‐ Lactobacillus ‐dominant state, have been shown to be associated with a range of adverse reproductive health outcomes, including increasing the risk of genital inflammation and HIV acquisition. Gardnerella vaginalis and Prevotella bivia have been shown to contribute to both HIV risk and genital inflammation. In addition to impacting HIV risk, the composition of the vaginal microbiome affects the vaginal concentrations of some antiretroviral drugs, particularly those administered intravaginally, and thereby their efficacy as pre‐exposure prophylaxis (PrEP) for HIV prevention. Although the role of rectal microbiota in HIV acquisition in women is less well understood, the composition of this compartment's microbiome, particularly the presence of species of bacteria from the Prevotellaceae family likely contribute to HIV acquisition. Advances in technologies have facilitated the study of the genital microbiome's structure and function. While next‐generation sequencing advanced knowledge of the diversity and complexity of the vaginal microbiome, the emerging field of metaproteomics, which provides important information on vaginal bacterial community structure, diversity and function, is further shedding light on functionality of the vaginal microbiome and its relationship with bacterial vaginosis (BV), as well as antiretroviral PrEP efficacy. Conclusions A better understanding of the composition, structure and function of the microbiome is needed to identify opportunities to alter the vaginal microbiome and prevent BV and reduce the risk of HIV acquisition.

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“…25 Furthermore, the integrity of epithelial cells isolated from the female genital tract was directly disrupted by the presence of HIV-1. 27 Re-epithelialization, the migration and proliferation of epithelial cells, 28 is an important step of mucosal wound repair, as well as that of skin and other tissues, sealing the epithelial defect and restoring barrier integrity. 27 Re-epithelialization, the migration and proliferation of epithelial cells, 28 is an important step of mucosal wound repair, as well as that of skin and other tissues, sealing the epithelial defect and restoring barrier integrity.…”

mentioning

confidence: 99%

Lactobacillus crispatus accelerates re‐epithelialization in vaginal epithelial cell line MS74

Takada

Komine‐Aizawa

Kuramochi

et al. 2018

American J Rep Immunol

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Microbiome Composition and Function Drives Wound-Healing Impairment in the Female Genital Tract

Cited by 113 publications

References 42 publications

The Vaginal Microbiome and its Potential to Impact Efficacy of HIV Pre-exposure Prophylaxis for Women

The Vaginal Microbiome and its Potential to Impact Efficacy of HIV Pre-exposure Prophylaxis for Women

The genital tract and rectal microbiomes: their role in HIV susceptibility and prevention in women

Lactobacillus crispatus accelerates re‐epithelialization in vaginal epithelial cell line MS74

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