Changes to the cervicovaginal microbiota and cervical cytokine profile following surgery for cervical intraepithelial neoplasia

Kawahara, Rina; Fujii, Takuma; Kukimoto, Iwao; Nomura, Hiroyuki; Kawasaki, Rie; Nishio, Eiji; Ichikawa, Ryoko; Tsukamoto, Tetsuya; Iwata, Aya

doi:10.1038/s41598-020-80176-6

Cited by 14 publications

(12 citation statements)

References 42 publications

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“…To further investigate the microbiome associated with OC, we summarized the differences in the microbiome composition between patients with or without OC using various α- (within-sample richness and evenness) and β- (between-sample) diversity measures. After adjusting for batch differences where necessary (See Methods), we compared the vaginal and cervical samples, and the results showed no significant differences (unweighted UniFrac: p = 0.814) between them in agreement with results from our previous studies 19 , 23 . We therefore combined the vaginal and cervical samples (lower reproductive tract, LRT) by adding sequence reads from both body sites for each patient in the rest of the present analysis.…”

Section: Resultssupporting

confidence: 82%

Diagnostic and prognostic potential of the microbiome in ovarian cancer treatment response

Asangba

Goergen

Larson

et al. 2023

Sci Rep

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Ovarian cancer (OC) is the second most common gynecological malignancy and the fifth leading cause of death due to cancer in women in the United States mainly due to the late-stage diagnosis of this cancer. It is, therefore, critical to identify potential indicators to aid in early detection and diagnosis of this disease. We investigated the microbiome associated with OC and its potential role in detection, progression as well as prognosis of the disease. We identified a distinct OC microbiome with general enrichment of several microbial taxa, including Dialister, Corynebacterium, Prevotella, and Peptoniphilus in the OC cohort in all body sites excluding stool and omentum which were not sampled from the benign cohort. These taxa were, however, depleted in the advanced-stage and high-grade OC patients compared to early-stage and low-grade OC patients suggestive of decrease accumulation in advanced disease and could serve as potential indicators for early detection of OC. Similarly, we also observed the accumulation of these mainly pathogenic taxa in OC patients with adverse treatment outcomes compared to those without events and could also serve as potential indicators for predicting patients’ responses to treatment. These findings provide important insights into the potential use of the microbiome as indicators in (1) early detection of and screening for OC and (2) predicting patients’ response to treatment. Given the limited number of patients enrolled in the study, these results would need to be further investigated and confirmed in a larger study.

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Section: Resultssupporting

confidence: 82%

Diagnostic and prognostic potential of the microbiome in ovarian cancer treatment response

Asangba

Goergen

Larson

et al. 2023

Sci Rep

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“…There is a growing body of clinical evidence suggesting that cervical procedures may disrupt this crucial communication between cervical and vaginal epithelium, and lead to changes in the composition of vaginal microbiome. 41, 42 Our results support this observation and suggest that it is a direct effect of reducing cervical mucus transfer to the vagina, which could only be studied directly using this type of engineered in vitro model.…”

Section: Resultssupporting

confidence: 75%

Modulation of dysbiotic vaginal complications by cervical mucus revealed in linked human vagina and cervix chips

Gutzeit,

Gulati,

Izadifar

et al. 2023

Preprint

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BackgroundThe cervicovaginal mucus that coats the upper surface of the vaginal epithelium is thought to serve as a selective barrier that helps to clear pathogens, however, its role in modulating the physiology and pathophysiology of the human vagina is poorly understood. Bacterial vaginosis (BV), a common disease of the female reproductive tract that increases susceptibility to sexually transmitted infections, pelvic inflammatory disease, infertility, preterm birth, and both maternal and neonatal infections is characterized by the presence of a wide array of strict and facultative anaerobes, often includingGardnerella vaginalis.ObjectiveTo assess the role of cervical mucus in preventing dysbiosis-associated complications and preserving vaginal health.Study DesignTo better understand the role of cervicovaginal mucus in vaginal health, we used human organ-on-a-chip (Organ Chip) microfluidic culture technology to analyze the effects of cervical mucus produced in a human Cervix Chip when transferred to a human Vagina Chip BV model. Both chips are lined by primary human organ-specific (cervical or vaginal) epithelium interfaced with organ-specific stromal fibroblasts.ResultsOur data show that mucus-containing effluents from Cervix Chips protect Vagina Chips from inflammation and epithelial cell injury caused by co-culture with dysbiotic microbiome containingG. vaginalis. Proteomic analysis of proteins produced by the Vagina Chip following treatment with the Cervix Chip mucus also revealed a collection of differentially abundant proteins that may contribute to the vaginal response to dysbiotic microbiome, which could represent potential diagnostic biomarkers or therapeutic targets for management of BV.ConclusionsThis study highlights the importance of cervical mucus in control of human vaginal physiology and pathophysiology, and demonstrates the potential value of Organ Chip technology for studies focused on health and diseases of the female reproductive tract.

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“…A lot of evidence is available to support the fact that the microbiome may lead to the persistence of an HPV infection and result in cervical neoplasia [4]. Coping with an HPV infection and the subsequent carcinogenesis may be associated with a balanced microbiome and its fight mechanisms [6,12]. Finding the best form of treatment by studying the cervicovaginal microbiome after various forms of intraepithelial neoplasia treatment is a new approach.…”

Section: Discussionmentioning

confidence: 99%

“…Human papilloma virus (HPV) is the most common factor responsible for the development of cervical intraepithelial neoplasia lesions. Some studies highlighted the importance of the microbiome in the development of a persistent HPV infection and its influence on progression to malignancy [2,4,6]. Some authors were hesitant whether an HPV infection was the cause of dysbiosis or dysbiosis was a risk factor of developing a persistent HPV infection [4].…”

Section: Introductionmentioning

confidence: 99%

Cervicovaginal Microbiome after Cervical Intraepithelial Neoplasia Treatment. A Protocol for Systematic Review and Meta-Analysis

Janicka-Kośnik¹,

Sarecka-Hujar

Jakiel

et al. 2021

IJERPH

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(1) Background: The microbiome consists of microorganisms from various kingdoms with numerous physical and chemical properties Lactobacillus species constitute the highest percentage of healthy cervical and vaginal microbiota. Dysbiosis may cause adverse outcomes, e.g., bacterial vaginosis, pelvic inflammatory disease and pregnancy complications. The cervicovaginal microbiome might contribute to the development of a persistent HPV infection—the main risk factor of cervical cancer—and influence progression to malignancy The aim is to perform a systematic review of current literature and a meta-analysis regarding microbiome changes after cervical intraepithelial neoplasia treatment. (2) Methods: We will search PubMed, Scopus, Google Scholar and Embase Database and trace citations in the reference sections. Randomized and non-randomized controlled studies, case–control and cohort studies published between January 2000 and May 2021 will be included in the study protocol. The following keywords will be used: ‘microbiome’, ‘vaginal microbiome’, ‘cervical microbiome’, ‘cervical neoplasia treatment’, ’conization’, ‘electroconization’, and ‘electrosurgical treatment’. Statistical analyses will be performed using RevMan 5.4. (3) Results: The results will be published as a peer-reviewed article. (4) Conclusions: The study will show which forms of intraepithelial neoplasia treatment change the cervicovaginal microbiome. Finding the best form of treatment by studying the cervicovaginal microbiome after various forms of treatment is essential. Patients would benefit not only from the treatment of the initial disease but also the management of dysbiosis, which might underlie other pathologies.

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Changes to the cervicovaginal microbiota and cervical cytokine profile following surgery for cervical intraepithelial neoplasia

Cited by 14 publications

References 42 publications

Diagnostic and prognostic potential of the microbiome in ovarian cancer treatment response

Diagnostic and prognostic potential of the microbiome in ovarian cancer treatment response

Modulation of dysbiotic vaginal complications by cervical mucus revealed in linked human vagina and cervix chips

Cervicovaginal Microbiome after Cervical Intraepithelial Neoplasia Treatment. A Protocol for Systematic Review and Meta-Analysis

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