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The cervicovaginal microbiota is influenced by host physiology, immunology, lifestyle, and ethnicity. We hypothesized that there would be differences in the cervicovaginal microbiota among pregnant, nonpregnant, and menopausal women living in Puerto Rico (PR) with and without human papillomavirus (HPV) infection and cervical cancer. We specifically wanted to determine if the microbiota is associated with variations in cervical cytology. A total of 294 women, including reproductive-age nonpregnant (N = 196), pregnant (N = 37), and menopausal (N = 61) women, were enrolled. The cervicovaginal bacteria were characterized by 16S rRNA amplicon sequencing, the HPV was genotyped with SPF10-LiPA, and cervical cytology was quantified. High-risk HPV (HR-HPV, 67.3%) was prevalent, including genotypes not covered by the 9vt HPV vaccine. Cervical lesions (34%) were also common. The cervical microbiota was dominated by Lactobacillus iners. Pregnant women in the second and third trimesters exhibited a decrease in diversity and abundance of microbes associated with bacterial vaginosis. Women in menopause had greater alpha diversity, a greater proportion of facultative and strictly anaerobic bacteria, and higher cervicovaginal pH than premenopausal women. Cervical lesions were associated with greater alpha diversity. However, no significant associations between the microbiota and HPV infection (HR or LR-HPV types) were found. The cervicovaginal microbiota of women living in Puerto Rican were either dominated by L. iners or diverse microbial communities regardless of a womans physiological stage. We postulate that the microbiota and the high prevalence of HR-HPV increase the risk of cervical lesions among women living in PR. IMPORTANCE In the enclosed manuscript, we provide the first in-depth characterization of the cervicovaginal microbiota of Hispanic women living in Puerto Rico (PR), using a 16S rRNA approach, and include women of different physiological stages. Surprisingly we found that high-risk HPV was ubiquitous with a prevalence of 67.3%, including types not covered by the 9vt HPV vaccine. We also found highly diverse microbial communities across women groups-with a reduction in pregnant women, but dominated by nonoptimal Lactobacillus iners. Additionally, we found vaginosis-associated bacteria as Dialister spp., Gardnerella spp., Clostridium, or Prevotella among most women. We believe this is a relevant and timely article expanding knowledge on the cervicovaginal microbiome of PR women, where we postulate that these highly diverse communities are conducive to cervical disease.

Abstract Cervical cancer is a common malignancy in women, with high incidence rate and mortality. Persistent infection of high-risk human papillomavirus (HPV) is the most important risk factor for cervical cancer and precancerous lesions. Cervicovaginal microbiota (CVM) plays an essential role in the defense of HPV infections and prevention of subsequent lesions. Dominance of Lactobacillus is the key of CVM homeostasis, which can be regulated by host, exogenous and endogenous factors. Dysbiosis of CVM, including altered microbial, metabolic, and immune signatures, can contribute to persist HPV infection, leading to cervical cancer. However, there is no evidence of the causality between CVM and cervical cancer, and the underlying mechanism remains unexplored. Considering the close correlation between CVM dysbiosis and persistent HPV infection, this review will overview CVM, its role in cervical cancer development and related mechanisms, and the prospects for therapeutic applications.

Abstract Background Cervicovaginal microbiome plays an important role in the persistence of HPV infection and subsequent disease development. However, cervicovaginal microbiota varied cross populations with different habits and regions. Identification of population-specific biomarkers from cervicovaginal microbiota and host metabolome axis may support early detection or surveillance of HPV-induced cervical disease at all sites. Therefore, in the present study, to identify HPV-specific biomarkers, cervicovaginal secretion and serum samples from HPV-infected patients (HPV group, n = 25) and normal controls (normal group, n = 17) in Xichang, China were collected for microbiome (16S rRNA gene sequencing) and metabolome (UHPLC-MS/MS) analysis, respectively. Results The results showed that key altered metabolites of 9,10-DiHOME, α-linolenic acid, ethylparaben, glycocholic acid, pipecolic acid, and 9,12,13-trihydroxy-10(E),15(Z)-octadecadienoic acid, correlating with Sneathia (Sneathia_amnii), Lactobacillus (Lactobacillus_iners), Atopobium, Mycoplasma, and Gardnerella, may be potential biomarkers of HPV infection. Conclusion The results of current study would help to reveal the association of changes in cervicovaginal microbiota and serum metabolome with HPV infections.

Cervical cancer is a common malignancy in women, with high incidence rate and mortality. Persistent infection of high-risk human papillomavirus (HPV) is the most important risk factor for cervical cancer and precancerous lesions. Cervicovaginal microbiota (CVM) plays an essential role in the defense of HPV infections and prevention of subsequent lesions. Dominance of Lactobacillus is the key of CVM homeostasis, which can be regulated by host, exogenous and endogenous factors. Dysbiosis of CVM, including altered microbial, metabolic, and immune signatures, can contribute to persist HPV infection, leading to cervical cancer. However, there is no evidence of the causality between CVM and cervical cancer, and the underlying mechanism remains unexplored. Considering the close correlation between CVM dysbiosis and persistent HPV infection, this review will overview CVM, its role in cervical cancer development and related mechanisms, and the prospects for therapeutic applications. [ABSTRACT FROM AUTHOR]

Background: The importance of Cervicovaginal Microbiota in protecting against infections (such as HPV) is already well established, namely through Lactobacillus spp., as well as the mechanism through which HPV leads to Cervical Neoplasia. However, it is not possible to classify HPV as a complete carcinogen. Thus, the importance of exploring Cervicovaginal dysbiosis with the intention of deciphering this interaction with HPV, takes on greater relevance. The main objectives of this study were: 1) Comparison of the MCV composition of women with or without HPV and women with ASCUS or LSIL; 2) Characterization of cytokines present in the vaginal microenvironment; 3) Evaluation of the blood count ratios as prognostic systemic inflammatory biomarkers; 4) Correlation between MCV, HPV serotypes and cytokines. Methods: This was a retrospective, observational, multicenter, cross-sectional study. CVM analysis was performed by isolation RNA and sequencing on a NGS platform. Cytokine concentrations of CVM were obtained through Multiplex platform. Statistical analysis was performed in SPSS v 26.0. An a of 0.05 was considered statistically significant. Results: Highlighting the core of the study, CVM types of CST I and CST IV were found to influence the emergence of cervical lesions. Neutrophil-to-Lymphocyte ratio was found to impact the prognosis of ASCUS. Within CVM, Lactobacillus prevent the growth of other CST IV species, while the latter express symbiotic relationships with each other and show affinity for specific HPV serotypes. At last, RANTES chemokine is significantly elevated in cervicovaginal infections. Conclusion: The importance of using vaginal cytokine profiles and CVM is highlighted in the hypothesis of prevention of Cervical Neoplasia development, as well as in its use as a prognostic biomarker. Taken together, these insights are one step closer to personalized medicine. [ABSTRACT FROM AUTHOR]

Introduction: Human papilloma virus (HPV) is the most common sexually transmitted infection worldwide. Cervicovaginal microbiota plays an important role in HPV infection and is associated with the development of squamous intraepithelial lesions (SIL). The natural history of cervical cancer involves reversible changes in the cervical tissue from a normal state, in which no neoplastic changes are detected in the squamous epithelium, to varying states of cellular abnormalities that ultimately lead to cervical cancer. Lowgrade SIL (LSIL), like another cytological category - atypical squamous cells of undetermined significance (ASCUS), may progress to high-grade SIL (HSIL) and invasive cervical cancer or may regress to a normal state. Methods: In this work, we studied cervical canal microbiome in 165 HPVpositive and HPV-negative women of a reproductive age with ASCUS [HPV(+) n = 29; HPV(-) n = 11], LSIL [HPV(+) n = 32; HPV(-) n = 25], HSIL [HPV(+) n = 46], and the control group with negative for intraepithelial lesion malignancy (NILM) [HPV(-) n = 22]. Results and Discussion: HPV16 is the most prevalent HPV type. We have not found any differences between diversity in studied groups, but several genus [like Prevotella (p-value = 0.026), Gardnerella (p-value = 0.003), Fannyhessea (p-value = 0.024)] more often occurred in HSIL group compared by NILM or LSIL regardless of HPV. We have found statistically significant difference in occurrence or proportion of bacterial genus in studied groups. We also identified that increasing of the ratio of Lactobacillus iners or age of patient lead to higher chance to HSIL, while increasing of the ratio of Lactobacillus crispatus lead to higher chance to LSIL. Patients with a moderate dysbiosis equally often had either of three types of vaginal microbial communities (CST, Community State Type) with the prevalence of Lactobacillus crispatus (CST I), Lactobacillus gasseri (CST II), and Lactobacillus iners (CST III); whereas severe dysbiosis is linked with CST IV involving the microorganisms genera associated with bacterial vaginosis and aerobic vaginitis: Gardnerella, Fannyhessea, Dialister, Sneathia, Anaerococcus, Megasphaera, Prevotella, Finegoldia, Peptoniphilus, Porphyromonas, Parvimonas, and Streptococcus. [ABSTRACT FROM AUTHOR]

Background: Cervicovaginal microbiome plays an important role in the persistence of HPV infection and subsequent disease development. However, cervicovaginal microbiota varied cross populations with different habits and regions. Identification of population-specific biomarkers from cervicovaginal microbiota and host metabolome axis may support early detection or surveillance of HPV-induced cervical disease at all sites. Therefore, in the present study, to identify HPV-specific biomarkers, cervicovaginal secretion and serum samples from HPV-infected patients (HPV group, n = 25) and normal controls (normal group, n = 17) in Xichang, China were collected for microbiome (16S rRNA gene sequencing) and metabolome (UHPLC-MS/MS) analysis, respectively. Results: The results showed that key altered metabolites of 9,10-DiHOME, α-linolenic acid, ethylparaben, glycocholic acid, pipecolic acid, and 9,12,13-trihydroxy-10(E),15(Z)-octadecadienoic acid, correlating with Sneathia (Sneathia_amnii), Lactobacillus (Lactobacillus_iners), Atopobium, Mycoplasma, and Gardnerella, may be potential biomarkers of HPV infection. Conclusion: The results of current study would help to reveal the association of changes in cervicovaginal microbiota and serum metabolome with HPV infections. [ABSTRACT FROM AUTHOR]

Persistent human papillomavirus (HPV) infection can lead to cervical intraepithelial neoplasia (CIN) and cervical cancer, posing serious threats to the health of women. Although the cervicovaginal microbiota is strongly associated with CIN, the dynamics of the microbiota during CIN development are unknown. In this retrospective cohort study, we analyzed 3‐year longitudinal data from 72 patients diagnosed with a persistent HPV infection almost all caused by high‐risk HPV types. Patients were categorized into groups with HPV persistent infection (n = 37), progression to CIN (n = 16), and CIN regression (n = 19) based on infection outcome during the follow‐up period. Furthermore, 16S rRNA gene sequencing was performed on consecutively collected cervical samples to explore the composition and dynamics of the cervicovaginal microbiota during the development and regression of CIN. Our results showed that the composition of the cervicovaginal microbiota varied among women with different HPV infection outcomes and remained relatively stable during the follow‐up period. Notably, the serial follow‐up data showed that these microbial alterations were present for at least 1–2 years and occurred before pathologic changes. In addition, microbial markers that were highly discriminatory for CIN progression or regression were identified. This study provides evidence for a temporal relationship between changes in the cervicovaginal microbiota and the development of CIN, and our findings provide support for future microbial intervention strategies for CIN. [ABSTRACT FROM AUTHOR]

Background: Convincing studies demonstrated that cervicovaginal microbiota disorder and toll-like receptor 9 (TLR9) high expression were related to cervical carcinogenesis. However, the effects of cervicovaginal microbiota integration TLR9 in cervical cancerization are unclear. Based on the biological basis that unmethylated cytosine–phosphate–guanine (CpG) motifs of bacteria could activate TLR9, we explored the effects of cervicovaginal microbiota disorder and CpG motif–TLR9 axis change in cervical carcinogenesis. Methods: A total of 341 participants, including 124 normal cervical (NC), 90 low-grade cervical intraepithelial neoplasia (CIN1), 78 high-grade cervical intraepithelial neoplasia (CIN2/3) and 49 squamous cervical cancer (SCC), diagnosed by pathology were enrolled in the study. Here, metagenomic shotgun sequencing was used to reveal cervicovaginal microbiota characteristics, and TLR9 protein was detected by western blotting. Results: Our results showed that the diversity of cervicovaginal microbiota gradually increased along with the poor development of cervical lesions, showing the abundance of Lactobacillus crispatus and Lactobacillus iners decreased, while the abundance of pathogenic bacteria gradually increased. The level of TLR9 expression was gradually increased with cervicovaginal microbiota diversity increasing, the abundance of Lactobacillus decreasing, and we found a positive correlation dependency relationship (r = 0.384, P = 0.002) between TLR9 and GTCGTT motif content. Stratified analysis based on HPV16 infection, we found that the characteristics of cervicovaginal microbiota and increased TLR9 expression were also closely related to HPV16 infection. Conclusions: Cervicovaginal microbiota dysbiosis might lead to the CpG motif increased, which was closely associated with TLR9 high expression, and ultimately might promote the progression of cervical lesions. [ABSTRACT FROM AUTHOR]

IntroductionHuman papilloma virus (HPV) is the most common sexually transmitted infection worldwide. Cervicovaginal microbiota plays an important role in HPV infection and is associated with the development of squamous intraepithelial lesions (SIL). The natural history of cervical cancer involves reversible changes in the cervical tissue from a normal state, in which no neoplastic changes are detected in the squamous epithelium, to varying states of cellular abnormalities that ultimately lead to cervical cancer. Low-grade SIL (LSIL), like another cytological category - atypical squamous cells of undetermined significance (ASCUS), may progress to high-grade SIL (HSIL) and invasive cervical cancer or may regress to a normal state.MethodsIn this work, we studied cervical canal microbiome in 165 HPV-positive and HPV-negative women of a reproductive age with ASCUS [HPV(+) n = 29; HPV(−) n = 11], LSIL [HPV(+) n = 32; HPV(−) n = 25], HSIL [HPV(+) n = 46], and the control group with negative for intraepithelial lesion malignancy (NILM) [HPV(−) n = 22].Results and DiscussionHPV16 is the most prevalent HPV type. We have not found any differences between diversity in studied groups, but several genus [like Prevotella (p-value = 0.026), Gardnerella (p-value = 0.003), Fannyhessea (p-value = 0.024)] more often occurred in HSIL group compared by NILM or LSIL regardless of HPV. We have found statistically significant difference in occurrence or proportion of bacterial genus in studied groups. We also identified that increasing of the ratio of Lactobacillus iners or age of patient lead to higher chance to HSIL, while increasing of the ratio of Lactobacillus crispatus lead to higher chance to LSIL. Patients with a moderate dysbiosis equally often had either of three types of vaginal microbial communities (CST, Community State Type) with the prevalence of Lactobacillus crispatus (CST I), Lactobacillus gasseri (CST II), and Lactobacillus iners (CST III); whereas severe dysbiosis is linked with CST IV involving the microorganisms genera associated with bacterial vaginosis and aerobic vaginitis: Gardnerella, Fannyhessea, Dialister, Sneathia, Anaerococcus, Megasphaera, Prevotella, Finegoldia, Peptoniphilus, Porphyromonas, Parvimonas, and Streptococcus.

BackgroundThe importance of Cervicovaginal Microbiota in protecting against infections (such as HPV) is already well established, namely through Lactobacillus spp., as well as the mechanism through which HPV leads to Cervical Neoplasia. However, it is not possible to classify HPV as a complete carcinogen. Thus, the importance of exploring Cervicovaginal dysbiosis with the intention of deciphering this interaction with HPV, takes on greater relevance. The main objectives of this study were: 1) Comparison of the MCV composition of women with or without HPV and women with ASCUS or LSIL; 2) Characterization of cytokines present in the vaginal microenvironment; 3) Evaluation of the blood count ratios as prognostic systemic inflammatory biomarkers; 4) Correlation between MCV, HPV serotypes and cytokines.MethodsThis was a retrospective, observational, multicenter, cross-sectional study. CVM analysis was performed by isolation RNA and sequencing on a NGS platform. Cytokine concentrations of CVM were obtained through Multiplex platform. Statistical analysis was performed in SPSS v 26.0. An α of 0.05 was considered statistically significant.ResultsHighlighting the core of the study, CVM types of CST I and CST IV were found to influence the emergence of cervical lesions. Neutrophil-to-Lymphocyte ratio was found to impact the prognosis of ASCUS. Within CVM, Lactobacillus prevent the growth of other CST IV species, while the latter express symbiotic relationships with each other and show affinity for specific HPV serotypes. At last, RANTES chemokine is significantly elevated in cervicovaginal infections.ConclusionThe importance of using vaginal cytokine profiles and CVM is highlighted in the hypothesis of prevention of Cervical Neoplasia development, as well as in its use as a prognostic biomarker. Taken together, these insights are one step closer to personalized medicine.

The female genital tract (FGT) is an important site of human immunodeficiency virus (HIV) infection. Discerning the nature of HIV-specific local immune responses is crucial for identifying correlates of protection in HIV-exposed seronegative (HESN) individuals. The present study involved a comprehensive analysis of soluble immune mediators, secretory immunoglobulins (sIg), natural killer (NK) cells, CXCR5+ CD8+ T cells, T follicular helper (Tfh) cells, and T regulatory cells (Tregs) in the vaginal mucosa as well as the nature and composition of the cervicovaginal microbiome in HESN women. We found significantly elevated antiviral cytokines, soluble immunoglobulins, and increased frequencies of activated NK cells, CXCR5+ CD8+ T cells, and Tfh cells in HESN females compared to HIV-unexposed healthy (UH) women. Analysis of the genital microbiome of HESN women revealed a greater bacterial diversity and increased abundance of Gardnerella spp. in the mucosa. The findings suggest that the female genital tract of HESN females represents a microenvironment equipped with innate immune factors, antiviral mediators, and critical T cell subsets that protect against HIV infection. IMPORTANCE The vast majority of human immunodeficiency virus (HIV) infections across the world occur via the sexual route. The genital tract mucosa is thus the primary site of HIV replication, and discerning the nature of HIV-specific immune responses in this compartment is crucial. The role of the innate immune system at the mucosal level in exposed seronegative individuals and other HIV controllers remains largely unexplored. This understanding can provide valuable insights to improve vaccine design. We investigated mucosal T follicular helper (Tfh) cells, CXCR5+ CD8+ T cells, natural killer (NK) cells subsets, soluble immune markers, and microbiome diversity in HIV-exposed seronegative (HESN) women. We found a significantly higher level of mucosal CXCR5+ CD8+ T cells, CD4+ Tfh cells, activated NK cell subsets, and antiviral immune cell mediators in HESN women. We also found a higher abundance of Gardnerella spp., microbiome dysbiosis, and decreased levels of inflammatory markers to be associated with reduced susceptibility to HIV infection. Our findings indicate that increased distribution of mucosal NK cells, CXCR5+ CD8+ T cells, Tfh cells, and soluble markers in HIV controllers with a highly diverse cervicovaginal microbiome could contribute effectively to protection against HIV infection. Overall, our findings imply that future vaccine design should emphasize inducing these highly functional cell types at the mucosal sites.

(1) Background: Cervical cancer is a significant health concern, with the main cause being persistent infection with high-risk Human Papillomavirus (hrHPV). There is still no evidence for why viral persistence occurs in some women, but recent studies have revealed the interplay between cervical microbiota and hrHPV. This research aimed to characterize the cervicovaginal microbiota in cervical lesion progression and HPV infection status. (2) Methods: This study included 85 cervical specimens from women from the north-eastern region of Romania. DNA was isolated from cervical secretion for HPV genotyping and 16S ribosomal RNA gene NGS sequencing. (3) Results: Our study revealed a distinct pattern within the studied group when considering Lactobacillus species, which differs from findings reported in other populations. Specifically, the presence of Lactobacillus iners coupled with the absence of Lactobacillus crispatus alongside Atopobium spp., Prevotella spp., and Gardnerella spp. could serve as defining factors for severe cervical lesions. The results also showed a significant association between microbiota diversity, HPV infection, and cervical lesion progression. (4) Conclusions: As the microbiota profile seems to vary among different populations and individuals, a deeper comprehension of its composition has the potential to develop personalized detection and treatment approaches for cervical dysplasia and cancer. [ABSTRACT FROM AUTHOR]

ABSTRACT The cervicovaginal microbiota is influenced by host physiology, immunology, lifestyle, and ethnicity. We hypothesized that there would be differences in the cervicovaginal microbiota among pregnant, nonpregnant, and menopausal women living in Puerto Rico (PR) with and without human papillomavirus (HPV) infection and cervical cancer. We specifically wanted to determine if the microbiota is associated with variations in cervical cytology. A total of 294 women, including reproductive-age nonpregnant (N = 196), pregnant (N = 37), and menopausal (N = 61) women, were enrolled. The cervicovaginal bacteria were characterized by 16S rRNA amplicon sequencing, the HPV was genotyped with SPF10-LiPA, and cervical cytology was quantified. High-risk HPV (HR-HPV, 67.3%) was prevalent, including genotypes not covered by the 9vt HPV vaccine. Cervical lesions (34%) were also common. The cervical microbiota was dominated by Lactobacillus iners. Pregnant women in the second and third trimesters exhibited a decrease in diversity and abundance of microbes associated with bacterial vaginosis. Women in menopause had greater alpha diversity, a greater proportion of facultative and strictly anaerobic bacteria, and higher cervicovaginal pH than premenopausal women. Cervical lesions were associated with greater alpha diversity. However, no significant associations between the microbiota and HPV infection (HR or LR-HPV types) were found. The cervicovaginal microbiota of women living in Puerto Rican were either dominated by L. iners or diverse microbial communities regardless of a woman’s physiological stage. We postulate that the microbiota and the high prevalence of HR-HPV increase the risk of cervical lesions among women living in PR. IMPORTANCE In the enclosed manuscript, we provide the first in-depth characterization of the cervicovaginal microbiota of Hispanic women living in Puerto Rico (PR), using a 16S rRNA approach, and include women of different physiological stages. Surprisingly we found that high-risk HPV was ubiquitous with a prevalence of 67.3%, including types not covered by the 9vt HPV vaccine. We also found highly diverse microbial communities across women groups—with a reduction in pregnant women, but dominated by nonoptimal Lactobacillus iners. Additionally, we found vaginosis-associated bacteria as Dialister spp., Gardnerella spp., Clostridium, or Prevotella among most women. We believe this is a relevant and timely article expanding knowledge on the cervicovaginal microbiome of PR women, where we postulate that these highly diverse communities are conducive to cervical disease.

Abstract Background High‐risk human papillomavirus (hrHPV) infection is a key factor that alters cervicovaginal microbiota patterns and causes cervical intraepithelial neoplasias (CINs) or even cervical cancer. Although local excisional treatment can clear hrHPV infection and restore the cervicovaginal microbiota, it is unclear which cervicovaginal microbiota represents recovery. Our objective was to describe the cervicovaginal microbiota before and after treatments and to assess the association between the microbiota and HPV persistence. Results A cohort of 91 participants was classified into four groups (healthy control women and HPV16‐infected women with CIN I, CIN II/III, and squamous cell carcinoma [SCC]). Endocervical swabs were collected 3 months prior to treatment and at 3 months post‐treatment for bacterial 16S rRNA gene pyrosequencing and for HPV DNA testing. There was an increase in the number of Lactobacillus bacterial species present after the clinical treatments, and the community state type (CST) profiles were shifted from dysbiotic CSTs II and IV to Lactobacillus‐dominated CSTs I and III. Specifically, the composition of Geobacter and Prevotella before treatment and Lactobacillus secaliphilus after treatment might have been related to CIN I, the composition of Burkholderia before treatment and Lactobacillus iners after treatment might have been related to CIN II/III, and the composition of Atopobium and Aerococcus before treatment and Bacilli after treatment might have been related to SCC. Further functional predictions revealed that the composition differences were linked to infectious disease‐ and cancer‐related genes. Conclusion Our study provides an illustration of the changes in CSTs and the cervicovaginal microbiota before and after HPV16 clearance in each disease state.

Bovine genital campylobacteriosis (BGC) is a leading cause of return to estrus in cows. The etiologic agent, Campylobacter fetus subsp. venerealis (Cfv) is transmitted by venereal route. Hence, the surrounding reproductive tract microenvironment could play a role in return to estrus in cows. The presence of Cfv in cervicovaginal mucus of Angus breed females provide three experimental groups, which were subject to bacteriome analyses: 10 Cfv-positive cows (CVP), 10 Cfv-negative cows (CVN), and 10 nonsexually active heifers (NSA). Cows with return to estrus showed higher bacterial richness than NSA. Beta diversity analysis showed a significant difference (P = 0.006) in bacterial composition among the three groups analyzed (CVP, CVN, and NSA). However, no significant difference was found when comparing the CVP versus CVN groups. Ureaplasma and Pseudomonas were the genera most frequently observed in NSA, being Ureaplasma the predictor genus to that group, whereas Alistipes, Bacteroides, Rikenellaceae_RC9_gut_group, UCG-005 , and UCG-10 were both significantly more abundant and predictors genera in cows with return to estrus. Our results provide an overview of the cervicovaginal bacterial microbiota in cows harboring Cfv and improve the knowledge of the pathogenesis of BGC. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The female reproductive tract harbours hundreds of bacterial species and produces numerous metabolites. The uterine cervix is located between the upper and lower parts of the female genital tract. It allows sperm and birth passage and hinders the upward movement of microorganisms into a relatively sterile uterus. It is also the predicted site for sexually transmitted infection (STI), such as Chlamydia, human papilloma virus (HPV), and human immunodeficiency virus (HIV). The healthy cervicovaginal microbiota maintains cervical epithelial barrier integrity and modulates the mucosal immune system. Perturbations of the microbiota composition accompany changes in microbial metabolites that induce local inflammation, damage the cervical epithelial and immune barrier, and increase susceptibility to STI infection and relative disease progression. This review examined the intimate interactions between the cervicovaginal microbiota, relative metabolites, and the cervical epithelial-, immune-, and mucus barrier, and the potent effect of the host-microbiota interaction on specific STI infection. An improved understanding of cervicovaginal microbiota regulation on cervical microenvironment homeostasis might promote advances in diagnostic and therapeutic approaches for various STI diseases.

Purpose: The cervicovaginal microbiota is essential for maintaining the health of the female reproductive tract. However, whether cervicovaginal microbiota status prior to frozen embryo transfer (FET) associates with pregnancy outcomes is largely unexplored. Methods: Cervical mucus from 29 women who had undergone FET was collected. Microbial composition was analyzed using 16 S rRNA gene sequence to assess the correlation to the pregnancy outcomes. Results: CST‐categorized Lactobacillus was the most dominant (41.71%) in the pregnant group, while CST‐IV‐based and BV‐related Gardnerella (34.96%) prevailed in the non‐pregnant group. The average abundance of Gardnerella compared non‐pregnant to pregnant women was the highest (34.96% vs. 4.22%, p = 0.0015) among other CST‐IV indicator bacteria. Multivariate analysis revealed that CST‐IV‐related bacteria have a significantly adverse effect on ongoing pregnancy outcomes (odds ratio, 0.083; 95% confidence index, 0.012–0.589, p = 0.013*). Conclusions: The study found that the CST‐IV microbiota, with significantly increasing Gardnerella and the loss of Lactobacilli as the dominant bacteria, can potentially contribute to pregnancy failure. Therefore, dysbiotic microbiota may be a risk factor in women undergoing FET. Assessing the health of the cervicovaginal microbiota prior to FET would enable couples to make a more thoughtful decision on the timing and might improve pregnancy outcomes. [ABSTRACT FROM AUTHOR]

The advent of high-throughput technologies, such as 16s rDNA sequencing, has significantly contributed to expanding our knowledge of the microbiota composition of the genital tract during infections such as Chlamydia trachomatis. The growing body of metagenomic data can be further exploited to provide a functional characterization of microbial communities via several powerful computational approaches. Therefore, in this study, we investigated the predicted metabolic pathways of the cervicovaginal microbiota associated with C. trachomatis genital infection in relation to the different Community State Types (CSTs), via PICRUSt2 analysis. Our results showed a more rich and diverse mix of predicted metabolic pathways in women with a CST-IV microbiota as compared to all the other CSTs, independently from infection status. C. trachomatis genital infection further modified the metabolic profiles in women with a CST-IV microbiota and was characterized by increased prevalence of the pathways for the biosynthesis of precursor metabolites and energy, biogenic amino-acids, nucleotides, and tetrahydrofolate. Overall, predicted metabolic pathways might represent the starting point for more precisely designed future metabolomic studies, aiming to investigate the actual metabolic pathways characterizing C. trachomatis genital infection in the cervicovaginal microenvironment. [ABSTRACT FROM AUTHOR]

There is evidence that coinfection of cervicovaginal high‐risk human papillomavirus (HR‐HPV) and bacteria is common in women of childbearing age. However, the relationship between bacterial vaginosis (BV) and persistent HR‐HPV infection in women of childbearing age and the underlying mechanisms remain unclear. In this study, we determined whether BV affects persistent HR‐HPV infection in women aged 20–45 years and explored the possible mechanisms of their interactions. From January 1 to April 30, 2020, we recruited women aged 20–45 years with and without BV at a ratio of 1:2 from Fujian Maternity and Child Health Hospital. All women were followed up at 0, 12, and 24 months. A BV assay, HR‐HPV genotyping and cervical cytology were performed at each follow‐up. At 0 months, additional vaginal secretions and cervical exfoliated cells were collected for 16S ribosomal RNA sequencing, bacterial metabolite determination, and POU5F1B, C‐myc, TLR4, NF‐κB, and hTERT quantification. A total of 920 women were included. The abundance of Prevotella (p = 0.016) and Gardnerella (p = 0.027) were higher, whereas the abundance of Lactobacillus was lower (p = 0.001) in women with persistent HR‐HPV infection and high‐grade squamous intraepithelial lesions (HSIL). The abundance of Prevotella (p = 0.025) and Gardnerella (p = 0.018) increased in the vaginas of women with persistent HPV16 infection, whereas only the abundance of Prevotella (p = 0.026) was increased in women with persistent HPV18 infection. The abundance of Prevotella in the vagina was significantly positively correlated with the expression levels of TLR4, NF‐κB, C‐myc, and hTERT in host cervical cells (p < 0.05). Our findings suggest that overgrowth of Prevotella in the vagina may influence the occurrence of persistent HR‐HPV infection‐related cervical lesions through host NF‐κB and C‐myc signaling. [ABSTRACT FROM AUTHOR]

The human papillomavirus (HPV) is a well-known oncovirus whose causal link in the occurrence and development of several cancers, such as cervical cancer (CC), has been well established. Indeed, numerous researches depicted the etiological role of HPV in CC pathogenesis in such a way as to develop efficient strategies, including early diagnoses and HPV vaccination, to mitigate HPV infection and CC occurrence. Despite the effectiveness of these strategies in preventing HPV infection, its persistence, and the progression to precancerous lesions and cancers, extensive work that could give a better understanding of other unknown factors favoring oncogenesis is much more needed. In this last decade, scarce or few but crucial and strategic studies have been carried out to improve and deepen our understanding of the etiopathological role of HPV in the progression towards the development of CC. In this review, we highlighted the recent findings on the pathological role of HPV in CC occurrence and the advances in novel adopted strategies to reduce HPV infection and prevent CC occurrence more effectively.

Abstract Purpose The cervicovaginal microbiota is essential for maintaining the health of the female reproductive tract. However, whether cervicovaginal microbiota status prior to frozen embryo transfer (FET) associates with pregnancy outcomes is largely unexplored. Methods Cervical mucus from 29 women who had undergone FET was collected. Microbial composition was analyzed using 16 S rRNA gene sequence to assess the correlation to the pregnancy outcomes. Results CST‐categorized Lactobacillus was the most dominant (41.71%) in the pregnant group, while CST‐IV‐based and BV‐related Gardnerella (34.96%) prevailed in the non‐pregnant group. The average abundance of Gardnerella compared non‐pregnant to pregnant women was the highest (34.96% vs. 4.22%, p = 0.0015) among other CST‐IV indicator bacteria. Multivariate analysis revealed that CST‐IV‐related bacteria have a significantly adverse effect on ongoing pregnancy outcomes (odds ratio, 0.083; 95% confidence index, 0.012–0.589, p = 0.013*). Conclusions The study found that the CST‐IV microbiota, with significantly increasing Gardnerella and the loss of Lactobacilli as the dominant bacteria, can potentially contribute to pregnancy failure. Therefore, dysbiotic microbiota may be a risk factor in women undergoing FET. Assessing the health of the cervicovaginal microbiota prior to FET would enable couples to make a more thoughtful decision on the timing and might improve pregnancy outcomes.

Human papillomavirus (HPV) clearance is important in eliminating cervical cancer which contributes to high morbidity and mortality in women. Nevertheless, it remains largely unknown about key players in clearing preexisting HPV infections. HPV antigens can be detected by the most important cervical antigen-presenting cells (Langerhans cells, LCs), of which the activities can be affected by cervicovaginal microbiota. In this review, we first introduce persistent HPV infections and then describe HPV-suppressed LCs activities, including but not limited to antigen uptake and presentation. Given specific transcriptional profiling of LCs in cervical epithelium, we also discuss the impact of cervicovaginal microbiota on LCs activation as well as the promise of exploring key microbial players in activating LCs and HPV-specific cellular immunity. [ABSTRACT FROM AUTHOR]

In healthy women, the cervicovaginal microbiota is characterized by the predominance of Lactobacillus spp., whereas the overgrowth of anaerobic bacteria leads to dysbiosis, known to increase the risk of acquiring genital infections like Chlamydia trachomatis. In the last decade, a growing body of research has investigated the composition of the cervicovaginal microbiota associated with chlamydial infection via 16s rDNA sequencing, with contrasting results. A systematic review and a meta-analysis, performed on the alpha-diversity indices, were conducted to summarize the scientific evidence on the cervicovaginal microbiota composition in C. trachomatis infection. Databases PubMed, Scopus and Web of Science were searched with the following strategy: "Chlamydia trachomatis" AND "micro*". The diversity indices considered for the meta-analysis were Operational Taxonomic Unit (OTU) number, Chao1, phylogenetic diversity whole tree, Shannon's, Pielou's and Simpson's diversity indexes. The search yielded 425 abstracts for initial review, of which 16 met the inclusion criteria. The results suggested that the cervicovaginal microbiota in C. trachomatis-positive women was characterized by Lactobacillus iners dominance, or by a diverse mix of facultative or strict anaerobes. The meta-analysis, instead, did not show any difference in the microbial biodiversity between Chlamydia-positive and healthy women. Additional research is clearly required to deepen our knowledge on the interplay between the resident microflora and C. trachomatis in the genital microenvironment. [ABSTRACT FROM AUTHOR]

Lower female genital tract is colonized by a variety of microbes (cervicovaginal microbiota, CVM) which associate with the risk of genital infection. This study characterized CVM for 149 Chinese women with different status of human papillomavirus (HPV) infection and squamous intraepithelial lesion (SIL): no HPV infection (HPV-), HPV infection without significant SIL (HPV+NoSIL), HPV infection with low-grade SIL (HPV+LSIL) and HPV infection with high-grade SIL (HPV+HSIL). Analysis results showed CVM has dramatically changed in HPV+HSIL group when compared to HPV+LSIL group, but it exhibited no significant differences between HPV- and HPV+NoSIL groups as well as between HPV+NoSIL and HPV+LSIL groups. In consistence, random forest analysis found more notable differences in HPV+HSIL vs HPV+LSIL comparison than in other comparisons. In addition, depletion of Lactobacillus in CVM was more to be frequently identified in SILpositive women as compared to SIL-negative individuals. Our findings suggested that significant CVM differences occurred when SIL developed to HSIL which was caused by persistent HPV infection. [ABSTRACT FROM AUTHOR]

ABSTRACT Cervical cancer is the third leading cause of female cancers globally, resulting in more than 300,000 deaths every year. The majority of all cervical cancers are caused by persistent infections with high-risk human papillomaviruses (hrHPV) that can progress to cancer via a series of premalignant lesions. Most women, however, clear this infection within a year, concomitant with disease regression. Both hrHPV clearance and disease regression have been associated with the composition of the cervicovaginal microenvironment, which is defined by the host immune system and the cervicovaginal microbiome (CVM). A healthy microbiome is generally characterized by a high abundance of Lactobacillus species, and a change in the composition may cause bacterial vaginosis (BV), which is associated with an increased susceptibility to persistent hrHPV infections and disease. In this review, the composition of the CVM is discussed, with emphasis on the possible causes that drive changes in the cervicovaginal microbiota in relation to hrHPV infections, disease progression, and disease regression. The literature search focused on the composition of the CVM and its correlation with hrHPV infections and neoplastic lesions as well as the current efforts to adjust the microbiome against adverse viral outcomes.

Lower female genital tract is colonized by a variety of microbes (cervicovaginal microbiota, CVM) which associate with the risk of genital infection. This study characterized CVM for 149 Chinese women with different status of human papillomavirus (HPV) infection and squamous intraepithelial lesion (SIL): no HPV infection (HPV-), HPV infection without significant SIL (HPV+NoSIL), HPV infection with low-grade SIL (HPV+LSIL) and HPV infection with high-grade SIL (HPV+HSIL). Analysis results showed CVM has dramatically changed in HPV+HSIL group when compared to HPV+LSIL group, but it exhibited no significant differences between HPV- and HPV+NoSIL groups as well as between HPV+NoSIL and HPV+LSIL groups. In consistence, random forest analysis found more notable differences in HPV+HSIL vs HPV+LSIL comparison than in other comparisons. In addition, depletion of Lactobacillus in CVM was more to be frequently identified in SIL-positive women as compared to SIL-negative individuals. Our findings suggested that significant CVM differences occurred when SIL developed to HSIL which was caused by persistent HPV infection.

The microbiome, which refers to the microbiota within a host and their collective genomes, has recently been demonstrated to play a critical role in cancer progression, metastasis, and therapeutic response. The microbiome is known to affect host immunity, but its influence on human papilloma virus (HPV) gynecologic malignancies remains limited and poorly understood. To date, studies have largely focused on the cervicovaginal microbiome; however, there is growing evidence that the gut microbiome may interact and substantially affect therapeutic response in gynecologic cancers. Importantly, new developments in microbiome sequencing and advanced bioinformatics technologies have enabled rapid advances in our understanding of the gut and local tumor microbiota. In this review, we examine the evidence supporting the role of the microbiome in HPV-associated cervical intraepithelial neoplasia (CIN) and cervical cancer, explore characteristics that influence and shape the host microbiota that impact HPV-driven carcinogenesis, and highlight potential approaches and considerations for future and ongoing research of the microbiome's effect on HPV-associated cancer.

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.

Cervical intraepithelial neoplasia (CIN) is a precancerous condition inducing local lesions on the surface of the squamocolumnar junction of the cervix. Despite the role of vaginal microbiota having been under-discussed, the role of the cervical microbiome and the microbial migration across the reproductive tract involved in CIN was limitedly studied. We aimed to synchronously characterize the dysbiosis associated with CIN in both the cervix and vagina in a Chinese population. Profiling of cervical and vaginal microbiota from 60 CIN women and 60 healthy women was conducted. 16S rRNA sequencing was adopted. By comparing the microbial profiles between different parts of the reproductive tract, our results demonstrated an increased shift of microbial diversity in the cervix compared with that in the vagina for the CIN patients, specifically in CIN 1. Less dysbiosis was found between the CIN patients and controls, in either the vagina or cervix. The microbial community may be modulated by the onset of sexual activity, a known clinical risk factor for cervical neoplasia. Distinct patterns of perturbated bacteria were found in the vaginal and cervical microbiota, in which reduced Actinobacteria-related operational taxonomic units (OTUs) and increased Proteobacteria-related OTUs were found in the vagina and cervix, respectively. A good agreement between the direction of the top-significant perturbated OTUs was observed between the vaginal and cervical microbiome, suggesting a potential microbial migration in the reproductive tract. Enriched genera such as Sphingomonas and Stenotrophomonas were found in cervical microbiota-associated CIN. Multivariate analysis revealed Comamonas , Rhizobium , and Pseudomonas as independent genera contributing to CIN in the cervix. In summary, this study revealed the perturbation of microbiota in the presence of CIN and demonstrated a distinct pattern of characteristic bacteria community between the vagina and cervix involved in the development of CIN. [ABSTRACT FROM AUTHOR]

Cervical intraepithelial neoplasia (CIN) is a precancerous condition inducing local lesions on the surface of the squamocolumnar junction of the cervix. Despite the role of vaginal microbiota having been under-discussed, the role of the cervical microbiome and the microbial migration across the reproductive tract involved in CIN was limitedly studied. We aimed to synchronously characterize the dysbiosis associated with CIN in both the cervix and vagina in a Chinese population. Profiling of cervical and vaginal microbiota from 60 CIN women and 60 healthy women was conducted. 16S rRNA sequencing was adopted. By comparing the microbial profiles between different parts of the reproductive tract, our results demonstrated an increased shift of microbial diversity in the cervix compared with that in the vagina for the CIN patients, specifically in CIN 1. Less dysbiosis was found between the CIN patients and controls, in either the vagina or cervix. The microbial community may be modulated by the onset of sexual activity, a known clinical risk factor for cervical neoplasia. Distinct patterns of perturbated bacteria were found in the vaginal and cervical microbiota, in which reduced Actinobacteria-related operational taxonomic units (OTUs) and increased Proteobacteria-related OTUs were found in the vagina and cervix, respectively. A good agreement between the direction of the top-significant perturbated OTUs was observed between the vaginal and cervical microbiome, suggesting a potential microbial migration in the reproductive tract. Enriched genera such as Sphingomonas and Stenotrophomonas were found in cervical microbiota-associated CIN. Multivariate analysis revealed Comamonas, Rhizobium, and Pseudomonas as independent genera contributing to CIN in the cervix. In summary, this study revealed the perturbation of microbiota in the presence of CIN and demonstrated a distinct pattern of characteristic bacteria community between the vagina and cervix involved in the development of CIN.

The advent of high-throughput technologies, such as 16s rDNA sequencing, has significantly contributed to expanding our knowledge of the microbiota composition of the genital tract during infections such as Chlamydia trachomatis. The growing body of metagenomic data can be further exploited to provide a functional characterization of microbial communities via several powerful computational approaches. Therefore, in this study, we investigated the predicted metabolic pathways of the cervicovaginal microbiota associated with C. trachomatis genital infection in relation to the different Community State Types (CSTs), via PICRUSt2 analysis. Our results showed a more rich and diverse mix of predicted metabolic pathways in women with a CST-IV microbiota as compared to all the other CSTs, independently from infection status. C. trachomatis genital infection further modified the metabolic profiles in women with a CST-IV microbiota and was characterized by increased prevalence of the pathways for the biosynthesis of precursor metabolites and energy, biogenic amino-acids, nucleotides, and tetrahydrofolate. Overall, predicted metabolic pathways might represent the starting point for more precisely designed future metabolomic studies, aiming to investigate the actual metabolic pathways characterizing C. trachomatis genital infection in the cervicovaginal microenvironment.

Background The cervicovaginal microbiota, including sexually transmitted infections (STIs), have not been well described in female genital schistosomiasis (FGS). Methods Women (aged 18–31, sexually active, nonpregnant) were invited to participate at the final follow-up of the HPTN 071 (PopART) Population Cohort in January–August 2018. We measured key species of the cervicovaginal microbiota (Lactobacillus crispatus , L. iners , Gardnerella vaginalis , Atopobium vaginae , and Candida) and STIs (Chlamydia trachomatis , Neisseria gonorrhoeae , Trichomonas vaginalis , and Mycoplasma genitalium) using quantitative PCR (qPCR). We evaluated associations of the microbiota and STI presence and concentration with FGS (qPCR-detected Schistosoma DNA in any of 3 genital specimens). Results The presence and concentration of key cervicovaginal species did not differ between participants with (n = 30) or without FGS (n = 158). A higher proportion of participants with FGS had T. vaginalis compared with FGS-negative women (P =.08), with further analysis showing that T. vaginalis was more prevalent among women with ≥2 Schistosoma qPCR-positive genital specimens (50.0%, 8/16) than among FGS-negative women (21.5%, 34/158; P =.01). Conclusions We found weak evidence of an association between the presence of T. vaginalis and FGS, with a stronger association in women with a higher-burden FGS infection. Additional research is needed on potential between-parasite interactions, especially regarding HIV-1 vulnerability. [ABSTRACT FROM AUTHOR]

In healthy women, the cervicovaginal microbiota is characterized by the predominance of Lactobacillus spp., whereas the overgrowth of anaerobic bacteria leads to dysbiosis, known to increase the risk of acquiring genital infections like Chlamydia trachomatis. In the last decade, a growing body of research has investigated the composition of the cervicovaginal microbiota associated with chlamydial infection via 16s rDNA sequencing, with contrasting results. A systematic review and a meta-analysis, performed on the alpha-diversity indices, were conducted to summarize the scientific evidence on the cervicovaginal microbiota composition in C. trachomatis infection. Databases PubMed, Scopus and Web of Science were searched with the following strategy: “Chlamydia trachomatis” AND “micro*”. The diversity indices considered for the meta-analysis were Operational Taxonomic Unit (OTU) number, Chao1, phylogenetic diversity whole tree, Shannon’s, Pielou’s and Simpson’s diversity indexes. The search yielded 425 abstracts for initial review, of which 16 met the inclusion criteria. The results suggested that the cervicovaginal microbiota in C. trachomatis-positive women was characterized by Lactobacillus iners dominance, or by a diverse mix of facultative or strict anaerobes. The meta-analysis, instead, did not show any difference in the microbial biodiversity between Chlamydia-positive and healthy women. Additional research is clearly required to deepen our knowledge on the interplay between the resident microflora and C. trachomatis in the genital microenvironment.

Objective  While select cervicovaginal microbiota and psychosocial factors have been associated with spontaneous preterm birth, their effect on the risk of recurrence remains unclear. It is also unknown whether psychosocial factors amplify underlying biologic risk. This study sought to determine the effect of nonoptimal cervicovaginal microbiota and perceived stress on the risk of recurrent spontaneous preterm birth. Study Design  This was a secondary analysis of a prospective pregnancy cohort, Motherhood and Microbiome. The Cohen's Perceived Stress Scale (PSS-14) was administered and cervical swabs were obtained between 16 and 20 weeks of gestation. PSS-14 scores ≥30 reflected high perceived stress. We analyzed cervicovaginal microbiota using 16S rRNA sequencing and classified microbial communities into community state types (CSTs). CST IV is a nonoptimal cervicovaginal microbial community characterized by anaerobes and a lack of Lactobacillus. The final cohort included a predominantly non-Hispanic Black population of women with prior spontaneous preterm birth who had recurrent spontaneous preterm birth or term birth and had stress measurements (n  = 181). A subanalysis was performed in the subset of these women with cervicovaginal microbiota data (n  = 74). Multivariable logistic regression modeled adjusted associations between CST IV and recurrent spontaneous preterm birth, high stress and recurrent spontaneous preterm birth, as well as high stress and CST IV. Results  Among the 181 women with prior spontaneous preterm birth, 45 (24.9%) had high perceived stress. We did not detect a significant association between high stress and recurrent spontaneous preterm birth (adjusted odds ratio [aOR] 1.67, 95% confidence interval [CI]: 0.73–3.85). Among the 74 women with prior spontaneous preterm birth and cervicovaginal microbiota analyzed, 29 (39.2%) had CST IV; this proportion differed significantly among women with recurrent spontaneous preterm birth (51.4%) compared with women with term birth (28.2%) (p  = 0.04). In models adjusted for race and marital status, the association between CST IV and recurrent spontaneous preterm birth persisted (aOR 3.58, 95% CI: 1.25–10.24). There was no significant interaction between stress and CST IV on the odds of spontaneous preterm birth (p  = 0.328). When both stress and CST IV were introduced into the model, their associations with recurrent spontaneous preterm birth were slightly stronger than when they were in the model alone. The aOR for stress with recurrent spontaneous preterm birth was 2.02 (95% CI: 0.61–6.71) and for CST IV the aOR was 3.83 (95% CI: 1.30–11.33). Compared to women with neither of the two exposures, women with both high stress and CST IV had the highest odds of recurrent spontaneous preterm birth (aOR = 6.01, 95% CI: 1.002–36.03). Conclusion  Among a predominantly non-Hispanic Black cohort of women with a prior spontaneous preterm birth, a nonoptimal cervicovaginal microbiota is associated with increased odds of recurrent spontaneous preterm birth. Adjustment for perceived stress may amplify associations between CST IV and recurrent spontaneous preterm birth. Identification of modifiable social or behavioral factors may unveil novel nonpharmacologic interventions to decrease recurrent spontaneous preterm birth among women with underlying biologic risk. Key Points CST IV, a nonoptimal microbiota, is associated with increased odds of recurrent spontaneous preterm birth. Adjustment for perceived stress amplified associations between CST IV and recurrent spontaneous preterm birth. Identification of modifiable psychosocial factors may unveil novel nonpharmacologic interventions to decrease recurrent preterm birth. [ABSTRACT FROM AUTHOR]

Background: Lactobacillus-deficient cervicovaginal microbiota is associated with spontaneous preterm birth and is more common among Black individuals. Persistent racial segregation in the United States has led to differential neighborhood exposures by race that can affect pregnancy outcomes. The extent to which neighborhood exposures may explain racial differences in the cervicovaginal microbiota is unknown., Objective: This study aimed to determine whether neighborhood deprivation, defined as material community deprivation, is associated with a Lactobacillus-deficient cervicovaginal microbiota in a prospective cohort of pregnant individuals. Our hypothesis was that racial differences in neighborhood deprivation may explain the higher prevalence of Lactobacillus-deficient cervicovaginal microbiota in Black birthing people., Study Design: This study analyzed data from Motherhood and Microbiome, a prospective pregnancy cohort enrolled from prenatal clinics in a single hospital system 2013-2016 in which a Lactobacillus-deficient cervicovaginal microbiota was previously shown to be associated with spontaneous preterm birth. This study geocoded addresses to obtain census tract neighborhood deprivation data from the Brokamp Nationwide Community Deprivation Index that uses weighted proportions of poverty, income, public assistance, lack of health insurance, and vacant housing. Generalized linear mixed models quantified associations of deprivation with the cervicovaginal microbiota accounting for geographic clustering by census tract and potential confounders. Because of different distributions of neighborhood deprivation and the cervicovaginal microbiota, race-stratified models were used. Mediation analyses quantified the extent to which deprivation may contribute to racial differences in the cervicovaginal microbiota., Results: Higher neighborhood deprivation was associated with a Lactobacillus-deficient cervicovaginal microbiota. Per standard deviation increment of deprivation, participants had 28% higher adjusted odds (adjusted odds ratio, 1.28; 95% confidence interval, 1.04-1.58) of a Lactobacillus-deficient microbiota. Black participants had higher odds of a Lactobacillus-deficient microbiota than White participants (adjusted odds ratio, 4.00; 95% confidence interval, 2.05-8.26), and mediation analysis revealed that deprivation accounted for 22% (P=.046) of that disparity., Conclusion: Neighborhood deprivation was associated with Lactobacillus-deficient cervicovaginal microbiota and may partially explain Black-White disparities in the cervicovaginal microbiota. Mechanistic studies to explore how environmental exposures modify the cervicovaginal microbiota are warranted to identify novel opportunities for future interventional strategies to prevent preterm birth. As the findings demonstrate a potential biological effect from neighborhood conditions, policies that drive urban planning should be explored to improve pregnancy outcomes., (Copyright © 2024 Elsevier Inc. All rights reserved.)

While the human microbiota especially that of the gut, cervix, and vagina continue to receive great attention, very little is currently known about the penile (glans, coronal sulcus, foreskin, and shaft) microbiota. The best evidences to date for the potential role of the penile microbiota in human immunodeficiency virus (HIV) and other sexually transmitted infections (STIs) acquisition have come from studies examining medical male circumcision. We are still at the foothills of identifying specific penile bacteria that could be associated with increased risk of STI/HIV acquisition. In this review, we summarize the available literature on the human penile microbiota and how it is impacted by circumcision. We also discuss the potential role of penile microbiota in STIs and its impact on cervicovaginal microbiota. Taken together, the findings from the penile microbiota studies coupled with observational studies on the effect of male circumcision for reduction of STI/HIV infection risk suggest that specific penile anaerobic bacteria such as Prevotella spp. potentially have a mechanistic role that increases the risk of genital infections and syndromes, including bacterial vaginosis in sexual partners. Although penile Corynebacterium and Staphylococcus have been associated with healthy cervicovaginal microbiota and have been found to increase following male circumcision, further investigations are warranted to ascertain the exact roles of these bacteria in the reproductive health of men and women. This review aims to address existing gaps and challenges and future prospects in the penile microbiota research. The information described here may have translational significance, thereby improving reproductive health and management of STI/HIV.

We aimed to analyze the strain-by-strain expression of a large panel of antimicrobial activities counteracting the virulence mechanisms of bacterial vaginosis-associated Prevotella bivia CI-1 and Gardnerella vaginalis 594, pyelonephritis-associated Escherichia coli CFT073, and recurrent cystitis- and preterm labor-associated IH11128 E. coli by Lactobacillus gasseri and Lactobacillus crispatus clinical strains, and L. gasseri ATCC 9857 and KS 120.1, and L. crispatus CTV-05 strains isolated from the cervicovaginal microbiota of healthy women. All L. gasseri and L. crispatus strains exerted antimicrobial activity by secreted lactic acid, which killed the microbial pathogens by direct contact. Potent bactericidal activity was exerted by a very limited number of resident L. gasseri and L. crispatus strains showing the specific ability to a strain to produce and release antibiotic-like compounds. These compounds eradicated the microbial pathogens pre-associated with the surface of cervix epithelial cells, providing efficient protection of the cells against the deleterious effects triggered by toxin-producing G. vaginalis and uropathogenic E. coli. Furthermore, these compounds crossed the cell membrane to kill the pre-internalized microbial pathogens. In addition, all L. gasseri and L. crispatus cells exhibited another non-strain specific activity which inhibited the association of microbial pathogens with cervix epithelial cells with varying efficiency, partially protecting the cells against lysis and detachment triggered by toxin-producing G. vaginalis and uropathogenic E. coli. Our results provide evidence of strain-level specificity for certain antimicrobial properties among cervicovaginal L. gasseri and L. crispatus strains, indicating that the presence of a particular species in the vaginal microbiota is not sufficient to determine its benefit to the host. A full repertory of antimicrobial properties should be evaluated in choosing vaginal microbiota-associated Lactobacillus isolates for the development of live biotherapeutic strategies.

We aimed to analyze the strain-by-strain expression of a large panel of antimicrobial activities counteracting the virulence mechanisms of bacterial vaginosis-associated Prevotella bivia CI-1 and Gardnerella vaginalis 594, pyelonephritis-associated Escherichia coli CFT073, and recurrent cystitis- and preterm labor-associated IH11128 E. coli by Lactobacillus gasseri and Lactobacillus crispatus clinical strains, and L. gasseri ATCC 9857 and KS 120.1, and L. crispatus CTV-05 strains isolated from the cervicovaginal microbiota of healthy women. All L. gasseri and L. crispatus strains exerted antimicrobial activity by secreted lactic acid, which killed the microbial pathogens by direct contact. Potent bactericidal activity was exerted by a very limited number of resident L. gasseri and L. crispatus strains showing the specific ability to a strain to produce and release antibiotic-like compounds. These compounds eradicated the microbial pathogens pre-associated with the surface of cervix epithelial cells, providing efficient protection of the cells against the deleterious effects triggered by toxin-producing G. vaginalis and uropathogenic E. coli. Furthermore, these compounds crossed the cell membrane to kill the pre-internalized microbial pathogens. In addition, all L. gasseri and L. crispatus cells exhibited another non-strain specific activity which inhibited the association of microbial pathogens with cervix epithelial cells with varying efficiency, partially protecting the cells against lysis and detachment triggered by toxin-producing G. vaginalis and uropathogenic E. coli. Our results provide evidence of strain-level specificity for certain antimicrobial properties among cervicovaginal L. gasseri and L. crispatus strains, indicating that the presence of a particular species in the vaginal microbiota is not sufficient to determine its benefit to the host. A full repertory of antimicrobial properties should be evaluated in choosing vaginal microbiota-associated Lactobacillus isolates for the development of live biotherapeutic strategies. [ABSTRACT FROM AUTHOR]

Background Vaginal dysbiosis, an imbalance between species, can initiate some local changes in immune and metabolic signaling causing chronic inflammation. The mechanism of the clearance or progression of the HPV infection has not been uncovered yet. We hypothesized that vaginal dysbiosis may contribute to the persistence of the cervical HPV infection. Therefore we aimed to determine the association of lactobacillus dominancy index with cervical HR-HPV persistence. Methods A total of 100 women who were followed up because of high-risk HPV infection were defined as the target study group. The patients were evaluated in two groups; HPV positive (group with HPV persistence, n=43) and HPV negative (group with HPV clearance, n=57). Cervicovaginal swab samples and blood samples were evaluated for Nugent score, lactobacillus dominance, and white blood cell count. Statistical tests were performed by the IBM Statistical Product and Service Solutions (version 22, IBM SPSS Statistics for Windows, Armonk, NY) program. The continuous variables were presented using the mean±standard deviation (SD), and the categorical variables were presented as the number of cases and their percentage. A p value less than 0.05 (<0.05) was set as statistically significant. Results HPV persistence was observed in 43 (43%) patients. Univariate analysis revealed that age, menopausal status, and lactobacillus reduction were associated with HPV persistence (p<0.05). The median value of the Nugent score was similar among groups. After logistic regression analysis, lactobacillus reduction continued to be associated with HPV persistence, independent of age and menopause (OR: 2.668, 96% CI: 1.069-6.662, p<0.05) Conclusions A decrease in lactobacilli in the cervicovaginal microbiota is associated with the persistence of HPV, regardless of age and menopausal status in this study., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Avsaroglu et al.)

Vaginal microbial communities can be dominated by anaerobic (community state type IV, CST IV) or Lactobacillus (other CSTs) species. CST IV is a risk factor for spontaneous preterm birth (sPTB) and is more common among Black than White populations. In the US, average air pollution exposures are higher among Black compared to White people and exert systemic health effects. We sought to (1) quantify associations of air pollution, specifically particulate matter <2.5 μm in diameter (PM 2.5), with CST IV and (2) explore the extent to which racial disparities in PM 2.5 exposure might explain racial differences in the prevalence of CST IV. Methods: We performed a secondary analysis of 566 participants of the Motherhood & Microbiome study. PM 2.5 exposures were derived from a machine learning model integrating NASA satellite and EPA ground monitor data. Previously, cervicovaginal swabs from 15 to 20 weeks' gestation were analyzed using 16 S rRNA sequencing and hierarchical clustering assigned CSTs. Multivariable logistic regression models calculated adjusted odds ratios of CST IV (vs. other CSTs) per interquartile range (IQR) increment of PM 2.5. Race-stratified and mediation analyses were performed. Higher PM 2.5 exposure was associated with CST IV (aOR 1.39, 95% CI 1.02–1.91). Further adjustment for race/ethnicity attenuated the association (aOR 1.34, 95% CI: 0.97–1.83). Black participants (vs. White) had higher median PM 2.5 exposure (10.6 vs. 9.6 μg/m3, P < 0.001) and higher prevalence of CST IV (47% vs. 11%, P < 0.001). Mediation analysis revealed that higher PM 2.5 exposure may explain 3.9% (P = 0.038) and 3.3% (P = 0.15) of the Black-White disparity in CST IV in unadjusted and adjusted models, respectively. PM 2.5 was associated with CST IV, a risk factor for sPTB. Additionally, PM 2.5 exposure may partially explain racial differences in the prevalence of CST IV. Further research is warranted to discover how environmental exposures affect microbial composition and perpetuate racial health disparities. • Pollution (PM 2.5) is associated with Lactobacillus -deficient vaginal microbiota. • PM 2.5 exposure and Lactobacillus -deficient vaginal microbiota differ by race. • PM 2.5 exposure may partly explain racial disparities in cervicovaginal microbiota. [ABSTRACT FROM AUTHOR]

The human cervicovaginal microbiota resides at an interface between the host and the environment and may affect susceptibility to disease. Puerto Rican women have high human papillomavirus (HPV) infection and cervical cancer rates. We hypothesized that the population structure of the cervicovaginal bacterial and fungal biota changed with cervical squamous intraepithelial lesions and HPV infections. DNA was extracted from cervix, introitus, and anal sites of 62 patients attending high-risk San Juan clinics. The 16S rRNA V4 region and ITS-2 fungal regions were amplified and sequenced using Illumina technology. HPV genotyping was determined by reverse hybridization with the HPV SPF10-LiPA25 kit. HPV prevalence was 84% of which ∼44% subjects were infected with high-risk HPV, ∼35% were co-infected with as many as 9 HPV types and ∼5% were infected with exclusively low-risk HPV types. HPV diversity did not change with cervical dysplasia. Cervical bacteria were more diverse in patients with CIN3 pre-cancerous lesions. We found enrichment of Atopobium vaginae and Gardnerella vaginalis in patients with CIN3 lesions. We found no significant bacterial biomarkers associated with HPV infections. Fungal diversity was significantly higher in cervical samples with high-risk HPV and introitus samples of patients with Atypical Squamous Cells of Undetermined Significance (ASCUS). Fungal biomarker signatures for vagina and cervix include Sporidiobolaceae and Sacharomyces for ASCUS, and Malassezia for high-risk HPV infections. Our combined data suggests that specific cervicovaginal bacterial and fungal populations are related to the host epithelial microenvironment, and could play roles in cervical dysplasia.

The human papillomavirus (HPV) is a well-known oncovirus whose causal link in the occurrence and development of several cancers, such as cervical cancer (CC), has been well established. Indeed, numerous researches depicted the etiological role of HPV in CC pathogenesis in such a way as to develop efficient strategies, including early diagnoses and HPV vaccination, to mitigate HPV infection and CC occurrence. Despite the effectiveness of these strategies in preventing HPV infection, its persistence, and the progression to precancerous lesions and cancers, extensive work that could give a better understanding of other unknown factors favoring oncogenesis is much more needed. In this last decade, scarce or few but crucial and strategic studies have been carried out to improve and deepen our understanding of the etiopathological role of HPV in the progression towards the development of CC. In this review, we highlighted the recent findings on the pathological role of HPV in CC occurrence and the advances in novel adopted strategies to reduce HPV infection and prevent CC occurrence more effectively., Competing Interests: The authors declare no conflict of interest., (© 2023 The Author(s). Published by IMR Press.)

The human cervicovaginal microbiota resides at an interface between the host and the environment and may affect susceptibility to disease. Puerto Rican women have high human papillomavirus (HPV) infection and cervical cancer rates. We hypothesized that the population structure of the cervicovaginal bacterial and fungal biota changed with cervical squamous intraepithelial lesions and HPV infections. DNA was extracted from cervix, introitus, and anal sites of 62 patients attending high-risk San Juan clinics. The 16S rRNA V4 region and ITS-2 fungal regions were amplified and sequenced using Illumina technology. HPV genotyping was determined by reverse hybridization with the HPV SPF10-LiPA25 kit. HPV prevalence was 84% of which ∼44% subjects were infected with high-risk HPV, ∼35% were co-infected with as many as 9 HPV types and ∼5% were infected with exclusively low-risk HPV types. HPV diversity did not change with cervical dysplasia. Cervical bacteria were more diverse in patients with CIN3 pre-cancerous lesions. We found enrichment of Atopobium vaginae and Gardnerella vaginalis in patients with CIN3 lesions. We found no significant bacterial biomarkers associated with HPV infections. Fungal diversity was significantly higher in cervical samples with high-risk HPV and introitus samples of patients with Atypical Squamous Cells of Undetermined Significance (ASCUS). Fungal biomarker signatures for vagina and cervix include Sporidiobolaceae and Sacharomyces for ASCUS, and Malassezia for high-risk HPV infections. Our combined data suggests that specific cervicovaginal bacterial and fungal populations are related to the host epithelial microenvironment, and could play roles in cervical dysplasia. [ABSTRACT FROM AUTHOR]

High‐risk (hr) human papillomavirus (HPV) infection is closely associated with the clinical conditions of both squamous intraepithelial lesions (SILs) and cervical carcinoma. However, it remains unclear what factors determine the type of hrHPV infection. Here, we have comprehensively investigated the bacterial composition of the cervicovaginal microbiota of 280 women infected with one type of hrHPV (HPV 16, 52 or 58) by the pyrosequencing of barcoded 16S rRNA genes. Differential microbiota composition was observed among various SIL groups and within the subgroups of each group. This result showed that it is not the microbiota diversity or the common microbiota, but rather agents that are specific to each SIL that might have a positive influence on the acquisition of hrHPV types, independent of abundance. Specifically, a composition of Oribacterium, Lachnobacterium and Thermus in the cervicovaginal microbiota is more likely to be associated with HPV 16, while a composition of Motilibacter in the cervicovaginal microbiota is more likely to be associated with HPV 52, and a composition of Litorilinea and Paludibaculum with a concomitant paucity of L. iners in the cervicovaginal microbiota is more likely to be associated with HPV 58. Furthermore, functional predictions regarding infectious diseases and cancer‐related genes disclosed significant differences (p < 0.01) among the different (sub)groups. Our study provides an elucidation of the relationship between the composition of the cervicovaginal microbiota and the type of hrHPV acquired. [ABSTRACT FROM AUTHOR]