Vaginal Microbiome in Women's Health

A special issue of Microorganisms (ISSN 2076-2607). This special issue belongs to the section "Microbiomes".

Deadline for manuscript submissions: closed (30 March 2024) | Viewed by 15719

Special Issue Editors


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Guest Editor
CBQF – Centro de Biotecnologia e Química Fina, Escola Superior de Biotecnologia, Universidade Católica Portuguesa, Porto, Portugal
Interests: fundamental studies of vaginal microbiome in relation to female health, focusing on dysbiosis profile, and the inherent strong association to gynaecological diseases

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Co-Guest Editor
CBQF – Centro de Biotecnologia e Química Fina, Escola Superior de Biotecnologia, Universidade Católica Portuguesa, Porto, Portugal
Interests: smart and advanced technologies to improve gynecological disorder’s theragnostic; study of bio-based alternative strategies and novel biomaterials to promote vaginal homeostasis and infection control

Special Issue Information

Dear Colleagues,

The human body is a holobiont, which is based on a dynamic synergy with billions of years of co-evolution. The host and multispecies microbes, as well as their inter-play abilities, were progressively improved, and nowadays, they are mostly symbiotic. The vaginal microbiome is no exception: it is an energetic microecosystem that undergoes constant fluctuations during the female menstrual cycle and throughout a woman's life. In this vaginal ecosystem, there is a homeostatic relationship between the microbiota and the host. The host provides a moist, nutritious, and warm habitat for the microbes, while the resident microbiota produces antimicrobial and anti-inflammatory factors. Therefore, they represent the first line of defence against non-indigenous microorganisms. Vaginal microbiome homeostasis plays a vital role in reproductive health. Depending on its composition, the microbiome can protect the vagina from infectious or non-infectious diseases, or it can increase its susceptibility. The diversity and dominant bacterial taxa in the vagina are influenced by multiple intrinsic factors including age, ancestry, pathologies, immune system, hormonal status, and pregnancy. Extrinsic factors include the use of contraceptives, antibiotics, and socioeconomic status. The variations of these internal and/or external factors lead to the breakdown of a balanced ecosystem, also known as dysbiosis. Lactobacillus species are associated with vaginal health, but the role of these species in maintaining health is not yet fully defined. Overall changes in the vaginal microbiome are often seen in women with dysbiosis, but the exact ethology of most disorders is still unknown. There are also other implications for the vaginal flora in non-infectious conditions such as pregnancy, preterm birth, fertility, cancer, and other aspects of women's health.

This Special Issue aims to describe the vaginal microbiome in relation to female health, discuss the characteristics of dysbiosis, present a strong association between these and common diseases, understand the genome impact on dysbiosis, and outline the need for comprehensive diagnostics and therapies accurate and advanced to reduce the prevalence of the female forum diseases.

Dr. Sandra F. Borges
Dr. Sara Baptista da Silva
Guest Editors

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Keywords

  • vaginal microbiome
  • dysbiosis
  • gynaecological disorder
  • genome impact
  • theragnostic

Published Papers (8 papers)

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Research

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14 pages, 1633 KiB  
Article
Characteristics of Vaginal Microbiota of Women of Reproductive Age with Infections
by Wanting Dong, Siyi Wang, Xi Wang, Guojin Xu, Qiuying Liu, Zheng Li, Na Lv, Yuanlong Pan, Qian Xiong, Donglai Liu and Baoli Zhu
Microorganisms 2024, 12(5), 1030; https://doi.org/10.3390/microorganisms12051030 - 20 May 2024
Viewed by 460
Abstract
The vaginal microbiota can be classified into five major community state types (CSTs) based on the bacterial content. However, the link between different CST subtypes and vaginal infection remains unclear. Here, we analyzed 2017 vaginal microbiota samples from women of a reproductive age [...] Read more.
The vaginal microbiota can be classified into five major community state types (CSTs) based on the bacterial content. However, the link between different CST subtypes and vaginal infection remains unclear. Here, we analyzed 2017 vaginal microbiota samples from women of a reproductive age with vaginal infections that were published in the last decade. We found that L. iners was the most dominant in 34.8% of the vaginal samples, followed by L. crispatus (21.2%). CST I was common in healthy individuals, whereas CST III and IV were associated with dysbiosis and infection. CST III-B, IV-A, IV-B, and IV-C0 were prevalent in patients with bacterial vaginosis (BV). Based on the relative abundance of bacteria at the (sub)genus level, a random forest classifier was developed to predict vaginal infections with an area under the curve of 0.83. We further identified four modules of co-occurring bacterial taxa: L. crispatus, Gardnerella, Prevotella, and Bacteroides. The functional prediction revealed that nucleotide biosynthesis pathways were upregulated in patients with human papilloma virus, and carbohydrate degradation pathways were downregulated in patients with BV. Overall, our study identified the bacterial signatures of healthy and infected vaginal microbiota, providing unique insights into the clinical diagnosis and health status prediction of women of a reproductive age. Full article
(This article belongs to the Special Issue Vaginal Microbiome in Women's Health)
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17 pages, 1279 KiB  
Article
Unlocking the Uterine Code: Microbiota, Immune Cells, and Therapy for Recurrent Reproductive Failure
by Svetla Blazheva, Svetlana Pachkova, Tatyana Bodurska, Petar Ivanov, Alexander Blazhev, Tzvetan Lukanov and Emiliana Konova
Microorganisms 2024, 12(3), 547; https://doi.org/10.3390/microorganisms12030547 - 9 Mar 2024
Viewed by 1007
Abstract
The uterine microbiota has been the subject of increasing study, but its interaction with the local immune system remains unclear. Successful embryo implantation relies on endometrial receptivity, which is pivotal for immunological tolerance to fetal antigens and precise regulation of inflammatory mediators. Emerging [...] Read more.
The uterine microbiota has been the subject of increasing study, but its interaction with the local immune system remains unclear. Successful embryo implantation relies on endometrial receptivity, which is pivotal for immunological tolerance to fetal antigens and precise regulation of inflammatory mediators. Emerging data suggest a dynamic interplay between endometrial microflora and the immune system, making dysbiosis a potential determinant of pregnancy outcomes. Imbalances in the regulation of immune cells in the endometrium and decidua have been associated with infertility, miscarriage, and obstetric complications. A thorough comprehension of the immune system in the female reproductive tract shows potential for improving women’s health and pregnancy outcomes. The objective of this study was to evaluate the patterns of endometrial microbiota in patients with recurrent implantation failure (RIF) and recurrent pregnancy loss (RPL) and to explore their implications for endometrial immune cells and chronic endometritis (CE). Immune cells in biopsies from 107 RIF and 93 RPL patients were examined using flow cytometry. The endometrial microbial composition was analyzed using real-time polymerase chain reaction (RT-PCR). The research uncovered disrupted endometrial microbiota in most women with RIF and RPL, which was often associated with significant effects on lymphocytes, T cells, and uNK cells. Full article
(This article belongs to the Special Issue Vaginal Microbiome in Women's Health)
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14 pages, 1221 KiB  
Article
Analysis of Vaginal Microbiota Variations in the Third Trimester of Pregnancy and Their Correlation with Preterm Birth: A Case-Control Study
by Catalin Prodan-Barbulescu, Felix Bratosin, Roxana Folescu, Estera Boeriu, Zoran Laurentiu Popa, Cosmin Citu, Adrian Ratiu, Ovidiu Rosca and Adrian Cosmin Ilie
Microorganisms 2024, 12(2), 417; https://doi.org/10.3390/microorganisms12020417 - 19 Feb 2024
Cited by 1 | Viewed by 909
Abstract
This study conducted a detailed analysis of the vaginal microbiota in pregnant women to explore its correlation with preterm birth (PTB) outcomes. The primary objective was to identify microbial variations associated with increased PTB risk. Secondary objectives included investigating how changes in microbial [...] Read more.
This study conducted a detailed analysis of the vaginal microbiota in pregnant women to explore its correlation with preterm birth (PTB) outcomes. The primary objective was to identify microbial variations associated with increased PTB risk. Secondary objectives included investigating how changes in microbial composition relate to the local immune environment and PTB. Utilizing a retrospective case–control design, the study involved pregnant women with liveborn infants between 2019 and 2023. In total, 89 women who delivered preterm and 106 term deliveries were included. Data collection focused on third-trimester vaginal cultures. Statistically significant differences were observed between the preterm and full-term groups in several areas. The median white blood cell count (10.2 × 103/mm3 vs. 7.6 × 103/mm3, p = 0.009) and neutrophil count (7.2 × 103/mm3 vs. 5.1 × 103/mm3, p < 0.001) were higher in the preterm group. Vaginal pH was also elevated in preterm births (5.6 vs. 4.4, p < 0.001), with a higher prevalence of bacterial vaginosis (29.2% vs. 12.3%, p = 0.001) as indicated by the Nugent Score. The study noted a significant association of PTB with the presence of Candida spp. (OR = 1.84, p = 0.018), Gardnerella vaginalis (OR = 2.29, p = 0.003), Mycoplasma hominis (OR = 1.97, p = 0.007), and Ureaplasma urealyticum (OR = 2.43, p = 0.001). Conversely, a reduction in Lactobacillus spp. correlated with a decreased PTB risk (OR = 0.46, p = 0.001). The study provides compelling evidence that specific vaginal microbiota components, particularly certain pathogenic bacteria and an altered Lactobacillus profile, are significantly associated with PTB risk. These findings highlight the potential of targeting microbial factors in strategies aimed at reducing PTB rates. Further research is necessary to fully understand the complex interplay between microbial dynamics, host immunity, and PTB outcomes. Full article
(This article belongs to the Special Issue Vaginal Microbiome in Women's Health)
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16 pages, 3140 KiB  
Article
Metronidazole Treatment Failure and Persistent BV Lead to Increased Frequencies of Activated T- and Dendritic-Cell Subsets
by Wenkosi Perez Qulu, Gugulethu Mzobe, Andile Mtshali, Marothi Peter Letsoalo, Farzana Osman, James Emmanuel San, Asavela Olona Kama, Nigel Garrett, Adrian Mindel, Anne Rompalo, Lenine J. P. Liebenberg, Derseree Archary, Aida Sivro and Sinaye Ngcapu
Microorganisms 2023, 11(11), 2643; https://doi.org/10.3390/microorganisms11112643 - 27 Oct 2023
Cited by 1 | Viewed by 1169
Abstract
Metronidazole (MDZ) treatment failure and bacterial vaginosis (BV) recurrence rates are high among African women. This cohort study identified genital immune parameters associated with treatment response by comparing vaginal microbiota and immune cell frequencies in endocervical cytobrushes obtained from 32 South African women [...] Read more.
Metronidazole (MDZ) treatment failure and bacterial vaginosis (BV) recurrence rates are high among African women. This cohort study identified genital immune parameters associated with treatment response by comparing vaginal microbiota and immune cell frequencies in endocervical cytobrushes obtained from 32 South African women with symptomatic BV pre- and post-metronidazole treatment. Cervical T- and dendritic-cell subsets were phenotyped using multiparameter flow cytometry and the composition of vaginal microbial communities was characterized using 16S rRNA gene sequencing. MDZ treatment led to a modest decrease in the relative abundance of BV-associated bacteria, but colonization with Lactobacillus species (other than L. iners) was rare. At 6 and 12 weeks, MDZ-treated women had a significant increase in the frequencies of CCR5+ CD4+ T cells and plasmacytoid dendritic cells compared to the pre-treatment timepoint. In addition, MDZ non-responders had significantly higher frequencies of activated CD4 T cells and monocytes compared to MDZ responders. We conclude that MDZ treatment failure was characterized by an increased expression of activated T- and dendritic-cell subsets that may enhance HIV susceptibility. These data suggest the need to further assess the long-term impact of MDZ treatment on mucosal immune response and the vaginal microbiota. Full article
(This article belongs to the Special Issue Vaginal Microbiome in Women's Health)
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14 pages, 2361 KiB  
Article
Cervicovaginal Microbiota Profiles in Precancerous Lesions and Cervical Cancer among Ethiopian Women
by Brhanu Teka, Kyoko Yoshida-Court, Ededia Firdawoke, Zewditu Chanyalew, Muluken Gizaw, Adamu Addissie, Adane Mihret, Lauren E. Colbert, Tatiana Cisneros Napravnik, Molly B. El Alam, Erica J. Lynn, Melissa Mezzari, Jhingran Anuja, Eva Johanna Kantelhardt, Andreas M. Kaufmann, Ann H. Klopp and Tamrat Abebe
Microorganisms 2023, 11(4), 833; https://doi.org/10.3390/microorganisms11040833 - 24 Mar 2023
Cited by 6 | Viewed by 2151
Abstract
Although high-risk human papillomavirus infection is a well-established risk factor for cervical cancer, other co-factors within the local microenvironment may play an important role in the development of cervical cancer. The current study aimed to characterize the cervicovaginal microbiota in women with premalignant [...] Read more.
Although high-risk human papillomavirus infection is a well-established risk factor for cervical cancer, other co-factors within the local microenvironment may play an important role in the development of cervical cancer. The current study aimed to characterize the cervicovaginal microbiota in women with premalignant dysplasia or invasive cervical cancer compared with that of healthy women. The study comprised 120 Ethiopian women (60 cervical cancer patients who had not received any treatment, 25 patients with premalignant dysplasia, and 35 healthy women). Cervicovaginal specimens were collected using either an Isohelix DNA buccal swab or an Evalyn brush, and ribosomal RNA sequencing was used to characterize the cervicovaginal microbiota. Shannon and Simpson diversity indices were used to evaluate alpha diversity. Beta diversity was examined using principal coordinate analysis of weighted UniFrac distances. Alpha diversity was significantly higher in patients with cervical cancer than in patients with dysplasia and in healthy women (p < 0.01). Beta diversity was also significantly different in cervical cancer patients compared with the other groups (weighted UniFrac Bray-Curtis, p < 0.01). Microbiota composition differed between the dysplasia and cervical cancer groups. Lactobacillus iners was particularly enriched in patients with cancer, and a high relative abundance of Lactobacillus species was identified in the dysplasia and healthy groups, whereas Porphyromonas, Prevotella, Bacteroides, and Anaerococcus species predominated in the cervical cancer group. In summary, we identified differences in cervicovaginal microbiota diversity, composition, and relative abundance between women with cervical cancer, women with dysplasia, and healthy women. Additional studies need to be carried out in Ethiopia and other regions to control for variation in sample collection. Full article
(This article belongs to the Special Issue Vaginal Microbiome in Women's Health)
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18 pages, 2676 KiB  
Article
Compositional Changes in the Vaginal Bacterial Microbiome of Healthy Pregnant Women across the Three Gestational Trimesters in Ismailia, Egypt
by Mariam E. Amin, Marwa Azab, Amro Hanora, Khaled Atwa and Sarah Shabayek
Microorganisms 2023, 11(1), 139; https://doi.org/10.3390/microorganisms11010139 - 5 Jan 2023
Cited by 2 | Viewed by 1922
Abstract
The composition of the vaginal microbiome may lead to adverse pregnancy outcomes. Normal pregnancy is associated with changes in the vaginal bacterial community composition, which tend to be more enriched with one or two Lactobacillus species promoting a healthy vagina and favorable birth [...] Read more.
The composition of the vaginal microbiome may lead to adverse pregnancy outcomes. Normal pregnancy is associated with changes in the vaginal bacterial community composition, which tend to be more enriched with one or two Lactobacillus species promoting a healthy vagina and favorable birth outcomes. The aim of the current study was to determine compositional changes in the healthy vaginal microbiome composition during the three trimesters of pregnancy in Ismailia, Egypt using Illumina MiSeq sequencing of the V3–V4 region of the 16S rRNA. The phylum Firmicutes and the genus Lactobacillus dominated across the three trimesters of pregnancy. L. iners was the most abundant species. However, L. coleohominis and L. reuteri represented the least dominant vaginal lactobacilli. Core microbiome analyses showed the Lactobacillus genus and L. iners species to have the highest prevalence in all the samples of our study groups. The phylum Firmicutes was found to be negatively correlated with almost all other vaginal phyla during pregnancy. Likewise, a negative correlation between Lactobacillus and almost all other genera was detected, including significant negative correlations with Dialister and Prevotella. Furthermore, negative correlations of L. iners were detected with almost all other species, including a significant negative correlation with L. helveticus, G. vaginalis, S. anginosus, and S. agalactiae. Full article
(This article belongs to the Special Issue Vaginal Microbiome in Women's Health)
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Review

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14 pages, 302 KiB  
Review
Vaginal Microbiota and HPV in Latin America: A Narrative Review
by Eduardo Tosado-Rodríguez, Ian Alvarado-Vélez, Josefina Romaguera and Filipa Godoy-Vitorino
Microorganisms 2024, 12(3), 619; https://doi.org/10.3390/microorganisms12030619 - 20 Mar 2024
Viewed by 1260
Abstract
With the expansion of human microbiome studies in the last 15 years, we have realized the immense implications of microbes in human health. The human holobiont is now accepted, given the commensal relationships with bacteria, fungi, parasites, viruses, and human cells. The cervicovaginal [...] Read more.
With the expansion of human microbiome studies in the last 15 years, we have realized the immense implications of microbes in human health. The human holobiont is now accepted, given the commensal relationships with bacteria, fungi, parasites, viruses, and human cells. The cervicovaginal microbiota is a specific case within the human microbiome where diversity is lower to maintain a chemical barrier of protection against infections. This narrative review focuses on the vaginal microbiome. It summarizes key findings on how native bacteria protect women from disease or predispose them to damaging inflammatory processes with an emphasis on the role of HPV infections in Latin America, one of the world’s regions with the highest cervical cancer prevalence. Full article
(This article belongs to the Special Issue Vaginal Microbiome in Women's Health)
28 pages, 763 KiB  
Review
Current Updates on the Role of Microbiome in Endometriosis: A Narrative Review
by Hooi-Leng Ser, Siu-Jung Au Yong, Mohamad Nasir Shafiee, Norfilza Mohd Mokhtar and Raja Affendi Raja Ali
Microorganisms 2023, 11(2), 360; https://doi.org/10.3390/microorganisms11020360 - 31 Jan 2023
Cited by 9 | Viewed by 4793
Abstract
Endometriosis affects approximately 6 to 10% of reproductive-age women globally. Despite much effort invested, the pathogenesis that promotes the development, as well as the progression of this chronic inflammatory disease, is poorly understood. The imbalance in the microbiome or dysbiosis has been implicated [...] Read more.
Endometriosis affects approximately 6 to 10% of reproductive-age women globally. Despite much effort invested, the pathogenesis that promotes the development, as well as the progression of this chronic inflammatory disease, is poorly understood. The imbalance in the microbiome or dysbiosis has been implicated in a variety of human diseases, especially the gut microbiome. In the case of endometriosis, emerging evidence suggests that there may be urogenital-gastrointestinal crosstalk that leads to the development of endometriosis. Researchers may now exploit important information from microbiome studies to design endometriosis treatment strategies and disease biomarkers with the use of advanced molecular technologies and increased computational capacity. Future studies into the functional profile of the microbiome would greatly assist in the development of microbiome-based therapies to alleviate endometriosis symptoms and improve the quality of life of women suffering from endometriosis. Full article
(This article belongs to the Special Issue Vaginal Microbiome in Women's Health)
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