Genital Microbiota Research Articles

Prevalence of Human Papillomavirus (HPV) among Females in the General Population of the Split and Dalmatia County and Its Association with Genital Microbiota and Infections: A Prospective Study.

We conducted a prospective study with the aim of determining HPV prevalence and type distribution in the general female population of Southern Croatia (SDC), and to detect the presence of other microorganisms in the lower part of the female reproductive system and their possible influence on the frequency of HPV infection. Data were collected during routine check-up exams. All participants were examined by a gynecologist, and cervico-vaginal scrapings/swabs were collected, for cytological (Pap smear) and microbiological (for bacterial growth, genital mycoplasmas, chlamydia, and HPV) analysis. Informed consent was obtained from all participants with accompanying questionnaire. A total of 1050 asymptomatic women living in SDC participated in the study during a one-year period, and 107 of them (10.2%) had HR-HPV infection. We found that the presence of some bacteria (Ureaplasma, Chlamydia, and Gardnerella) in the lower part of the female genital system has a positive correlation with the frequency of HPV infection and, consequently, a possible influence on faster progression to cervical dysplasia caused by HPV. We consider that inclusion of screening for sexually transmitted infections as monitoring in women with HPV infection could help to find women at risk of cervical cancer progression.

Can probiotics enhance fertility outcome? Capacity of probiotics as a single intervention to improve the feminine genital tract microbiota in non-symptomatic reproductive-aged women.

Modifications in vaginal and endometrial microbiome and microbiota have been associated with fewer implantation rates and poorest pregnancy outcomes. Therefore, its study has emerged as a new biomarker in reproductive medicine. Despite the numerous papers published on probiotic use for vaginal dysbiosis and their actual wide empiric use especially for infertile patients, there is still no clear answer to justify their recommendation. The impact of probiotics on the vaginal or endometrial microbiota has often been investigated under a symptomatic altered vaginal microbial ecosystem, such as bacterial vaginosis. However 50% of women with bacterial vaginosis are asymptomatic. Actual clinical practice guidelines clearly recommend the use of specific antimicrobial agents for the management of symptomatic vaginal infections. Assuming this should be the management as well for an infertile population, what should be the treatment for the 50% non-symptomatic women presenting unfavorable vaginal/endometrial microbiota? The aim of this review is to assess the capacity of probiotics as a single intervention to alter the feminine genital tract microbiota in non-symptomatic reproductive-aged women.

Celiac Disease Predisposition and Genital Tract Microbiota in Women Affected by Recurrent Pregnancy Loss.

The incidence of Idiopathic Recurrent Pregnancy Loss (RPL) is doubled in patients suffering from Celiac Disease (CD) compared to healthy populations. CD genetic components are HLA class II genes known as HLA-DQ2 and DQ8. Genetically susceptible women can remain asymptomatic even though they are exposed to a doubled risk of RPL compared to the general population. Furthermore, CD has been associated with microbiota alterations. The aim of this study is to evaluate endometrial and vaginal microbiota in HLA-DQ2/DQ8 positive and negative RPL patients compared to healthy pregnant women. Endometrial and vaginal microbiota of 3 subgroups were evaluated: 15 HLA-DQ2/DQ8 positive RPL women, 25 HLA DQ2/DQ8 negative RPL women (for a total of 40 RPL women) and 7 healthy fertile controls with previous uncomplicated pregnancies (all HLA-DQ2/DQ8 negative). The 2 RPL subgroups (HLA-DQ2/DQ8 positive and negative) showed a different endometrial and vaginal composition in the Lactobacillacae family compared to controls: Lactobacillus acidophilus was absent both in the vaginal and endometrial samples of RPL women, while Lactobaciluus iners, which can favor a less stable vaginal microbiota, was found only in RPL women (26.4% in HLA DQ2/DQ8 positive and 22.1% HLA DQ2/DQ8 negative) in both the vaginal and endometrial districts. In conclusion, both HLA DQ2/DQ8 positive-RPL and HLA DQ2/DQ8 negative-RPL women showed different endometrial and vaginal microbiota composition compared to healthy controls.

Microbiota of female genital tract – functional overview of microbial flora from vagina to uterine tubes and placenta

Microorganisms and eukaryotic human cells coexist in synergistic relationships in nearly every niche of the human body. The female genital tract consisting of the vagina, uterus with its cervix and endometrium, uterine tubes and ovaries - harbors its own typical microbiota, which accounts for 9 % of the total bacterial population in females. To this organ system, we also assigned the microbiome of the placenta, which has not been studied much until now. Among the spectrum of microbial species, the female genital tract is mainly dominated by Lactobacillus species, which are considered to be one of the simplest yet most important microbial communities. However, this relationship between macro- and micro-organisms seems to have a number of physiological functions, e.g., the vaginal and cervical microbiota have unique impact on reproductive health. The aim of this review was to provide current view on female genital tract microbiota and its role in reproductive health. We describe in detail the association of vaginal or tubal epithelium with microbiota or the role of microbiota in normal placental function.

The role of upper and lower genital tract microbiota alterations in term chorionamnionitis: A prospective study.

This study aimed to compare the dynamics of lower and upper genital tract microbiota in normal term pregnancy, histological chorioamnionitis (HCA), and clinical chorioamnionitis (CCA) patients to provide a reference for the diagnosis and treatment of chorioamnionitis (CAM) patients. We prospectively collected vaginal and cervical secretions, as well as placenta tissues, fetal membranes, and amniotic fluid from normal-term pregnant women, HCA and CCA patients. Then, we performed genomic DNA extraction and PCR amplification for all samples. The eligible samples were analyzed by 16S ribosomal RNA (16S rRNA) sequencing. Additionally, all placenta tissues were histopathologically examined, and neonatal pharyngeal swabs and placenta tissues from the HCA and CCA groups were subjected to microbial culture. A total of 85 term pregnant women were enrolled in this study, including 34 in the normal group (N), 37 in the HCA group, and 14 in the CCA group. A total of 171 qualified samples were analyzed by 16S rRNA sequencing. The results suggested that the cervical microbiota was highly similar to the vaginal microbiota in normal term parturients, with Lactobacillus as the dominant bacterium. Moreover, there was no difference in the alpha and beta diversity of vaginal microbiota between the N, HCA, and CCA groups at the genus level. Besides, no significant differences were detected in cervical microbiome among the three groups. Regarding intrauterine microorganisms, the N and HCA groups had similar microbial composition but were different from the CCA group. No microbe was detected in the placental tissue of normal term parturients, while some microorganisms were found in the intrauterine amniotic fluid and fetal membrane samples. Regardless of cultivation or 16S rRNA sequencing, an extremely low microbial positive rate was detected in HCA and CCA intrauterine samples. Compared to the normal group, Lactobacillus was significantly reduced in the CCA group intrauterine, and Ureaplasma and Enterococcus increased with no statistically significant. The N, HCA and CCA groups had similar composition of vaginal and cervical microflora. Some normal-term pregnant women can harbor non-pathogenic microbiota in the uterine cavity. Sterile inflammation is more frequent than microbial-associated inflammation in term HCA and CCA parturients.

Genital Microbiota and Outcome of Assisted Reproductive Treatment-A Systematic Review.

The balance between different bacterial species is essential for optimal vaginal health. Microbiome includes the host genome along with microorganism genomes and incorporates the biotic and abiotic factors, reflecting the habitat as a whole. A significant difference exists in the composition and number of the human microbiota in healthy individuals. About one-tenth of the total body microbiota exists in the urogenital tract and these can be identified by microscopy and culture-based methods, quantitative PCR, next generation and whole genome sequencing. The trend of delaying the planning of pregnancy to a later age nowadays has resulted in magnifying the use of assisted reproductive treatment (ART). Hence, genital microbiota and its impact on fertility has generated immense interest in recent years. In this systematic review, we searched the available evidence on the microbiota of the genital tract in women undergoing ART and studied the outcomes of IVF in different microbial compositions. Despite the inconsistency of the studies, it is evident that vaginal, cervical and endometrial microbiota might play a role in predicting ART outcomes. However, there is no clear evidence yet on whether the diversity, richness, quantity, or composition of species in the maternal genital tract significantly affects the outcomes in ARTs.

Nutrition as Personalized Medicine against SARS-CoV-2 Infections: Clinical and Oncological Options with a Specific Female Groups Overview.

Coronavirus disease 2019 (COVID-19) is a respiratory disease caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). It is acknowledged that vulnerable people can suffer from mortal complications of COVID-19. Therefore, strengthening the immune system particularly in the most fragile people could help to protect them from infection. First, general nutritional status and food consumption patterns of everyone affect the effectiveness of each immune system. The effects of nutrition could impact the level of intestinal and genital microbiota, the adaptive immune system, and the innate immune system. Indeed, immune system cells and mediators, which are crucial to inflammatory reaction, are in the structures of fats, carbohydrates, and proteins and are activated through vitamins (vit) and minerals. Therefore, the association of malnutrition and infection could damage the immune response, reducing the immune cells and amplifying inflammatory mediators. Both amount and type of dietary fat impact on cytokine biology, that consequently assumes a crucial role in inflammatory disease. This review explores the power of nutrition in the immune response against COVID-19 infection, since a specific diet could modify the cytokine storm during the infection phase. This can be of vital importance in the most vulnerable subjects such as pregnant women or cancer patients to whom we have deemed it necessary to dedicate personalized indications.

Genital microbiota of women using a 90 day tenofovir or tenofovir and levonorgestrel intravaginal ring in a placebo controlled randomized safety trial in Kenya

In a phase-IIa trial, we investigated the influence of 90 days continuous-delivery tenofovir (TFV) intravaginal rings (IVRs) with/without levonorgestrel (LNG) on the genital microbiota of Kenyan women. Eligible women (n = 27; 18–34 years; negative for HIV, sexually transmitted infections, and Amsel-bacterial vaginosis) were randomized 2:2:1 to use of IVRs containing TFV, TFV/LNG, or placebo. Using vaginal wall and IVR swabs at IVR insertion and removal, the genital microbial composition was determined using 16S rRNA gene sequencing. The presence of Candida spp. was determined using qPCR. The vaginal total bacterial burden appeared to decrease with TFV and TFV/LNG IVR use (log100.57 and log100.27 decrease respectively; p > 0.05). The TFV/LNG IVR was more ‘stabilizing’: 50% of the participants’ microbiota community state types remained unchanged and 50% shifted towards higher Lactobacillus abundance. Specifically, TFV/LNG IVR use was accompanied by increased abundances of Lactobacillus gasseri/hominis/johnsonii/taiwanensis (16.3-fold) and L. fermentum/reuteri/vaginalis (7.0-fold; all p < 0.01). A significant shift in the overall microbial α-diversity or β-diversity was not observed for either IVR, and IVR use did not influence Candida spp. prevalence. TFV/LNG and TFV IVRs did not adversely affect the genital microbiota and are safe to use. Our findings support further studies assessing their efficacy in preventing HIV/HSV-2 and unintended pregnancies.

Genital Microbiota of Women From Six Ethnic Groups With and Without Human Papillomavirus Infection in Shangri-La, China.

BackgroundA diversity of microorganisms is associated with human health and exists in a state of dynamic equilibrium. This diversity has direct implications for the assessment of susceptibility to infectious diseases, especially human papillomavirus (HPV) infection.MethodsHere, we investigated the relationships between HPV infection and vaginal, cervical, and gut microbiota composition and assessed the levels of genital immune mediators. We selected a multiethnic area in Yunnan Province, China, to collect samples from healthy women of childbearing age. A total of 82 healthy women of childbearing age were included in this study. Vaginal, cervical, and rectal swabs were collected to analyze the microbial community, and cytokines were analyzed in some samples.FindingsDifferent proportions and types of HPV infection were detected in cervical (44%), vaginal (18%), and rectal (18%) swabs. HPV detected in cervical swabs was generally a high-risk type, while low-risk HPV types were primarily detected in vaginal and rectal swabs. There were some differences in this proportion as well as in the microbial community composition among different ethnic groups. Rectal samples exhibited the highest diversity index, while vaginal samples displayed the lowest diversity index. Lactobacillus dominated most of the vaginal samples, was decreased in HPV-positive samples, and differed among different ethnic groups. However, the sequence proportion of Lactobacillus in the cervix exhibited the opposite trend in those affected by HPV infection. The dynamic balance between the potential pathogens Gardnerella and Lactobacillus determines the health of the female genital system.InterpretationThis study constitutes the first step toward personalized medicine for women’s reproductive health, wherein differences between the genital microbiomes of individuals would be considered in risk assessment and for subsequent disease diagnosis and treatment.

Metagenomic analysis of the microbiome of the upper reproductive tract: combating ovarian cancer through predictive, preventive, and personalized medicine

PurposeWe investigated whether ovarian cancer could alter the genital microbiota in a specific way with clinical values. Furthermore, we proposed how such changes could be envisioned in a paradigm of predictive, preventive, and personalized medicine (PPPM).MethodsThe samples were collected using cotton swabs from the cervical, uterine cavity, fallopian tubes, and ovaries of patients subjected to the surgical procedures for the malignant/benign lesions. All samples were then analyzed by metagenomic shotgun sequencing. The distribution patterns and characteristics of the microbiota in the reproductive tract of subjects were analyzed and were interpreted in relation to the clinical outcomes of the subjects.ResultsWhile the ovarian cancer was able to alter the genital microbiota, the bacteria were the dominant microorganisms in all samples across all cohorts in the study (median 99%). The microbiota of the upper female reproductive tract were mainly from the cervical, identified by low bacterial biomass and high bacterial diversity. Ovarian cancer had a distinct microbiota signature. The tubal ligation affects its microbial distribution. There were no different species on the surface of platinum-sensitive ovarian tissues compared to samples from platinum-resistant patients.ConclusionThe ovarian cancer–induced changes in microbiota magnify the potential of microbiota as a biotherapeutic modality in the treatment of ovarian cancer in this study and very likely for several malignancies and other conditions. Our findings demonstrated, for the first time, that microbiota could be dissected and applied in more specific fashion based on a predictive, preventive, and personalized medicine (PPPM) model in the treatment of ovarian cancer. Utilizing microbiota portfolio in a PPPM system in ovarian cancer would provide a unique opportunity to a clinically intelligent and novel approach in the treatment of ovarian cancer as well as several other conditions and malignancies.

Cervicovaginal DNA Virome Alterations Are Associated with Genital Inflammation and Microbiota Composition.

ABSTRACTWhile the link between the cervicovaginal bacterial microbiome, human papillomavirus (HPV) infection, and cervical cancer is recognized (P. Łaniewski, D. Barnes, A. Goulder, H. Cui, et al., Sci. Rep. 8:7593, 2018, http://dx.doi.org/10.1038/s41598-018-25879-7; A. Mitra, D. A. MacIntyre, Y. S. Lee, A. Smith, et al., Sci. Rep. 5:16865, 2015, http://dx.doi.org/10.1038/srep16865; A. Mitra, D. A. MacIntyre, J. R. Marchesi, Y. S. Lee, et al., Microbiome 4:58, 2016, http://dx.doi.org/10.1186/s40168-016-0203-0; J. Norenhag, J. Du, M. Olovsson, H. Verstraelen, et al., BJOG, 127:171–180, 2020, http://dx.doi.org/10.1111/1471-0528.15854; E. O. Dareng, B. Ma, A. O. Famooto, S. N. Adebamowo, et al., Epidemiol. Infect. 144:123–137, 2016, http://dx.doi.org/10.1017/S0950268815000965; A. Audirac-Chalifour, K. Torres-Poveda, M. Bahena-Roman, J. Tellez-Sosa et al., PLoS One 11:e0153274, 2016, http://dx.doi.org/10.1371/journal.pone.0153274; M. Di Paola, C. Sani, A. M. Clemente, A. Iossa, et al., Sci. Rep. 7:10200, 2017, http://dx.doi.org/10.1038/s41598-017-09842-6), the role of the cervicovaginal virome remains poorly understood. In this pilot study, we conducted metagenomic next-generation sequencing of cervicovaginal lavage specimens to investigate the relationship between the cervicovaginal DNA virome, bacterial microbiome, genital inflammation, and HPV infection. Specific virome alterations were associated with features of the local microenvironment related to HPV persistence and progression to cervical cancer. Cervicovaginal viromes clustered distinctly by genital inflammation state. Genital inflammation was associated with decreased virome richness and alpha diversity and an increased abundance of Anelloviridae species from the genus Alphatorquevirus. Lactobacillus bacteriophages were closely associated with increased Lactobacillus abundance, consistent with phage-host relationships. Interestingly, bacteria-bacteriophage transkingdom interactions were linked to genital inflammation and showed specific interactions with bacterial vaginosis-associated bacteria, including Gardnerella, Prevotella, and Sneathia. Taken together, our results reveal prominent virome interactions with features of the cervicovaginal microenvironment that are associated with HPV and cervical cancer. These findings expand our understanding of the cervicovaginal host-microbiome interactions in women’s health.IMPORTANCE HPV infection is an established risk factor for cervical cancer. However, more broadly, the role of the cervicovaginal virome in cervical cancer progression is not well understood. Here, we identified cervicovaginal DNA virome alterations associated with local microenvironment factors (vaginal microbiota and genital inflammation) that influence HPV persistence and progression to cervical cancer. These findings indicate that the cervicovaginal virome plays an important role in women’s health.

Identifying Predictive Bacterial Markers from Cervical Swab Microbiota on Pregnancy Outcome in Woman Undergoing Assisted Reproductive Technologies.

Background and aims: Failure of the embryo to implant causes about three-fourths of lost pregnancies. Female genital tract microbiota has been associated to Assisted Reproductive Technologies (ART) outcomes. The objective of this study was to analyze the microbiota of human cervical swab and to correlate these findings with the ART outcomes. Materials and Methods: In this study, 88 cervical swabs were collected from women undergoing ART cycles, with various causes of infertility, at the beginning of the ART protocols. After microbial DNA extraction, V3–V4 variable regions of the 16S rRNA gene were amplified and sequenced on the Illumina MiSeq platform. PEnalized LOgistic Regression Analysis (PELORA) was performed to identify clusters of bacterial populations with differential abundances between patients with unfavorable and favorable pregnancy outcome groups, respectively. Results: We identified a core of microorganisms at lower taxonomic levels that were predictive of women’s pregnancy outcomes. Statistically significant differences were identified at species levels with Lactobacillus salivarius, Lactobacillus rhamnosus among others. Moreover the abundance of Lactobacillus crispatus and iners, respectively increased and decreased in favorable group as compared to unfavorable group, resulted within the core of microorganisms associated to positive ART outcome. Although the predominance of lactobacilli is generally considered to be advantageous for ART outcome, we found that also the presence of Bifidobacterium (together with the other lactobacilli) was more abundant in the favorable group. Discussion: Cervix is colonized by microorganisms which can play a role in ART outcomes as seen by an overall decrease in embryo attachment rates and pregnancy rates in both fertile and infertile women. If confirmed in a larger cohort, the abundance of these bacteria can be useful not only as a marker of unfavorable pregnancy outcome but also they may open the way to new interventional strategies based on genital tract microbiota manipulation in order to increase the pregnancy rates in woman undergoing assisted reproductive technologies.

The Vaginal Microbiota in Pig-Tailed Macaques and Colonization with Neisseria gonorrhoeae (GC)

Pig-tailed macaques (Macaca nemestrina) may help advance our understanding of how the genital microbiota influences sexually transmitted infections. We characterized the vaginal microbiota and evaluated the effect of streptomycin (STR) treatment on GC colonization to aid the development of a macaque model of genital gonococcal infection.

Genital Microbiota of Reproductive-Age Women From Six Ethnic Groups With and Without Human Papillomavirus (HPV) Infection in Shangri-La, China

Genital Microbiota of Reproductive-Age Women From Six Ethnic Groups With and Without Human Papillomavirus (HPV) Infection in Shangri-La, China

Complementary and Alternative Treatments for Postpartum Uterine Diseases in Dairy Cows

The goal of treating postpartum uterine diseases in dairy cows is to reach clinical cure in a reasonable amount of time and to improve reproductive performance while minimizing milk and meat residue issues. The ultimate goal is to reduce the economic losses caused by uterine diseases. This article focuses on postpartum uterine diseasess in dairy cows, in particular acute puerperal metritis, pyometra and endometritis. The usual treatment approach for these conditions is systemic or local antibiotic therapy to control bacterial growth. Based on clinical signs and bacteria identification using dependent- and independent-based methods, antibiotic use appears to be the most logical and effective therapeutic approach. However, despite considerable research, the treatment of uterine diseasess remains a subject of considerable controversy in the literature. Although some local and systemic antibiotic therapies are effective at mitigating the consequences of postpartum uterine diseases, antibiotic use in the current global context is a serious concern because it is associated with selective pressures on bacteria and the emergence of resistant bacteria in humans and animals. Research on mucosal immunology and the genital microbiota of cows has improved our understanding of uterine involution and how pathological agents behave during uterine diseases in dairy cows. And while antibiotic therapy remains the most common therapeutic option chosen by veterinarian practitioners to treat PUDs, complementary and alternative veterinary medicine is increasingly being considered in response to a demand from animal owners. However, because of the small number of randomized clinical trials and a lack of evidence-based medicine, there is widespread concern regarding the adequacy of evidence for the efficacy and safety of complementary and alternative veterinary medicine. The objectives of this article are to describe uterine involution and the main postpartum uterine diseases that occur during the postpartum period in dairy cows, briefly review the current approaches to treating postpartum uterine diseases, and critically review the evidence pertaining to complementary and alternative veterinary medicine in postpartum reproductive veterinary medicine.

Characterization of the Gastrointestinal and Reproductive Tract Microbiota in Fertile and Infertile Pakistani Couples.

Simple SummaryWe describe microbial taxa associated with the gastrointestinal and reproductive tracts of married Pakistani couples. We highlight differences in microbial composition and diversity that are associated with fertile and infertile couples and provide a baseline for future in-depth studies to target the association of the human microbiome with infertility.The human microbiota is recognized as a vital “virtual” organ of the human body that influences human health, metabolism, and physiology. While the microbiomes of the gut, oral cavity, and skin have been extensively studied in the literature, relatively little work has been done on characterizing the microbiota of the human reproductive tract organs, and specifically on investigating its association to fertility. Here, we implemented a 16S ribosomal RNA (rRNA) amplicon sequencing approach to sequence and characterize the gut and genital tract microbiomes from several married Pakistani couples. The recruited individuals included 31 fertile and 35 infertile individuals, with ages ranging from 19–45 years. We identified several fluctuations in the diversity and composition of the gut and genital microbiota among fertile and infertile samples. For example, measures of α-diversity varied significantly between the genital samples donated by fertile and infertile men and there was overall greater between-sample variability in genital samples regardless of gender. In terms of taxonomic composition, Actinobacteria, Bacteroidetes, and Firmicutes fluctuated significantly between the gut microbiomes of fertile and infertile samples. Finally, biomarker analyses identified features (genera and molecular functions and pathways) that differed significantly between the fertile and infertile samples and in the past have been associated with bacterial vaginosis. However, we emphasize that 16S amplicon data alone has no bearing on individual health and is merely representative of microbial taxonomic differences that could also arise due to multiple other factors. Our findings, however, represent the first effort to characterize the microbiome associated with fertile and infertile couples in Pakistan and will hopefully pave the way for more comprehensive and broad-scale investigations in the future.

Comparison of Female Genital Tract Cytokine and Microbiota Signatures Induced by Initiation of Intramuscular DMPA and NET-EN Hormonal Contraceptives - a Prospective Cohort Analysis.

BackgroundCervicovaginal inflammation, bacterial microbiota and hormonal contraceptives all influence sexual and reproductive health. To date, the effects of intramuscular depo-medroxyprogesterone acetate (DMPA-IM) versus injectable norethisterone enanthate (NET-EN) on vaginal microbiota or cytokines have not been compared back-to-back, although in-vitro data suggest that DMPA-IM and NET-EN have different pharmacokinetic and biologic activities. This study aimed at comparing the effects of DMPA-IM versus NET-EN initiation on cervicovaginal cytokines and microbiota in women at high risk for sexually transmitted infections (STIs) assigned to the respective contraceptives.MethodsWe collected socio-demographic characteristics and vaginal samples from women initiating DMPA-IM (ECHO Trial; n = 53) and NET-EN (UChoose Trial; n = 44) at baseline and after two consecutive injections to assess cytokine concentrations by Luminex, vaginal microbiota by 16S rRNA gene sequencing, STIs, bacterial vaginosis (BV) and candidiasis.ResultsCytokine concentrations did not change significantly after initiating DMPA-IM or NET-EN, although NET-EN versus DMPA-IM-associated profiles were distinct. While the abundance of bacterial taxa associated with optimal and non-optimal microbiota fluctuated with DMPA-IM use, overall community composition did not significantly change with either contraceptive. HSV-2 serology, chlamydial infection, gonorrhoea and candidiasis did not influence the associations between contraceptive type and cervicovaginal cytokines or microbiota.ConclusionsBoth DMPA-IM and NET-EN use did not lead to broad inflammatory or microbiota changes in the female genital tract of sub-Saharan African women. This suggests that NET-EN is likely a viable option for contraception in African women at high risk of BV and STIs.

The role of gut and genital microbiota and the estrobolome in endometriosis, infertility and chronic pelvic pain.

Endometriosis is a chronic, burdensome condition that is historically understudied. Consequently, there is a lack of understanding of the etiology of the disease and its associated symptoms, including infertility and chronic pelvic pain (CPP). Endometriosis development is influenced by estrogen metabolism and inflammation, which are modulated by several factors including the microbiome and the estrobolome (the collection of genes encoding estrogen-metabolizing enzymes in the gut microbiome). Therefore, there is increasing interest in understanding the role of microbiota in endometriosis etiology. To date, there is no cure for endometriosis and treatment options often are ineffective. This manuscript will review the potential relationship between the microbiome and endometriosis, infertility and CPP and highlight the available data on the microbiome in relation to endometriosis and its related symptoms. The overarching goal of this manuscript is to inform future microbiome research that will lead to a deeper understanding of the etiology of the disease and possible diagnostic modalities and treatments. The potential impact of the microbiome on estrogen regulation modulated by the estrobolome, as well as inflammation and other endometriosis-promoting mechanisms within the genital tract, will be reviewed. The methodological limitations of microbiome-related studies will be critically assessed to provide improved guidelines for future microbiome and clinical studies. PubMed databases were searched using the following keywords: endometriosis AND microbiome, infertility AND microbiome, pelvic pain AND microbiome, IVF (in-vitro fertilization) AND microbiome, endometriosis AND infertility. Clinical and preclinical animal trials that were eligible for review, and related to microbiome and endometriosis, infertility or CPP were included. All available manuscripts were published in 2002-2021. In total, 28 clinical and 6 animal studies were included in the review. In both human and animal studies, bacteria were enriched in endometriosis groups, although there was no clear consensus on specific microbiota compositions that were associated with endometriosis, and no studies included infertility or CPP with endometriosis. However, bacterial vaginosis-associated bacteria and Lactobacillus depletion in the cervicovaginal microbiome were associated with endometriosis and infertility in the majority (23/28) of studies. Interpretation of endometrial studies is limited owing to a variety of methodological factors, discussed in this review. In addition, metadata outlining antibiotic usage, age, race/ethnicity, menopausal status and timing of sample collection in relation to diagnosis of endometriosis was not consistently reported. Animal studies (6/6) support a bidirectional relationship between the gut microbiota and endometriosis onset and progression. There is evidence that a dysbiotic gut or genital microbiota is associated with multiple gynecologic conditions, with mounting data supporting an association between the microbiome and endometriosis and infertility. These microbiomes likely play a role in the gut-brain axis, which further supports a putative association with the spectrum of symptoms associated with endometriosis, including infertility and CPP. Collectively, this review highlights the demand for more rigorous and transparent methodology and controls, consistency across the field, and inclusion of key demographic and clinical characteristics of disease and comparison participants. Rigorous study designs will allow for a better understanding of the potential role of the microbiome in endometriosis etiology and the relationship to other disorders of the female reproductive tract.

Lactoferrin for Prevention and Treatment of Anemia and Inflammation in Pregnant Women: A Comprehensive Review.

Pregnancy is a physiological state that demands higher level of nutrients, including vitamins and minerals, for the growth and maintenance of the fetus. Iron deficiency is a part of most common diet deficiencies in pregnancy and has high clinical significance leading to the development of syderopenic anemia and its consequences for mother and child, such as higher risk of perinatal death, susceptibility to infection, intra-uteral growth inhibition, prematurity and low birth weight. Hence, iron supplementation is recommended for pregnant women; however dietary intake of iron from most commercially available formulas is often insufficient due to iron-poor bioavailability, or have undesired side-effects in the gastrointestinal tract, resulting in a discouraging and distrustful attitude to such treatment. The results of numerous studies indicate that diet supplementation with lactoferrin (LTF), an iron-binding protein, may be advantageous in prophylaxis and treatment of iron deficiency anemia. LTF, administered orally, normalizes iron homeostasis, not only by facilitating iron absorption, but also by inhibiting inflammatory processes responsible for anemia of chronic diseases, characterized by a functional iron deficit for physiological processes. LTF also protects against infections and inflammatory complications, caused by diagnostic surgical interventions in pregnant women. Beneficial, multidirectional actions of LTF during pregnancy encompass, in addition, inhibition of oxidative stress, normalization of intestine and genital tract microbiota and carbohydrate-lipid metabolism, protection of intestine barrier function, promotion of wound healing, as well as hypotensive, analgesic and antistress actions. Bovine lactoferrin (BLTF) is readily available on the nutritional market and generally recognized as safe (GRAS) for use in human diet.

The impact of the female genital tract microbiome in women health and reproduction: a review.

The aim of this review is to gather the available research focusing on female genital tract (FGT) microbiome. Research question focuses in decipher which is the role of FGT microbiota in eubiosis, assisted reproduction techniques (ARTs), and gynaecological disorders, and how microbiome could be utilised to improve reproduction outcomes and to treat fertility issues. PubMed was searched for articles in English from January 2004 to April 2021 for "genital tract microbiota and reproduction", "endometrial microbiome", "microbiome and reproduction" and "microbiota and infertility". Manual search of the references within the resulting articles was performed. Current knowledge confirms predominance of Lactobacillus species, both in vagina and endometrium, whereas higher variability of species is both found in fallopian tubes and ovaries. Microbial signature linked to different disorders such endometriosis, bacterial vaginosis, and gynaecological cancers are described. Broadly, low variability of species and Lactobacillus abundance within the FGT is associated with better reproductive and ART outcomes. Further research regarding FGT microbiome configuration needs to be done in order to establish a more precise link between microbiota and eubiosis or dysbiosis. Detection of bacterial species related with poor reproductive outcomes, infertility or gynaecological diseases could shape new tools for their diagnosis and treatment, as well as resources to assess the pregnancy prognosis based on endometrial microbiota. Data available suggest future research protocols should be standardised, and it needs to include the interplay among microbiome, virome and mycobiome, and the effect of antibiotics or probiotics on the microbiome shifts.