Mobile genetic elements from the maternal microbiome shape infant gut microbial assembly and metabolism.

The perinatal period represents a critical window for cognitive and immune system development, promoted by maternal and infant gut microbiomes and their metabolites. Here, we tracked the co-development of microbiomes and metabolomes from late pregnancy to 1 year of age using longitudinal multi-omics data from a cohort of 70 mother-infant dyads. We discovered large-scale mother-to-infant interspecies transfer of mobile genetic elements, frequently involving genes associated with diet-related adaptations. Infant gut metabolomes were less diverse than maternal but featured hundreds of unique metabolites and microbe-metabolite associations not detected in mothers. Metabolomes and serum cytokine signatures of infants who received regular-but not extensively hydrolyzed-formula were distinct from those of exclusively breastfed infants. Taken together, our integrative analysis expands the concept of vertical transmission of the gut microbiome and provides original insights into the development of maternal and infant microbiomes and metabolomes during late pregnancy and early life.

Etiology and Diagnosis of Pelvic Inflammatory Disease: Looking Beyond Gonorrhea and Chlamydia.

Pelvic inflammatory disease (PID) is a clinical syndrome that has been associated with a wide range of potential causal pathogens. Three broad groups of organisms have been isolated from the genital tract of people with PID: sexually transmitted organisms such as Neisseria gonorrhoeae, Chlamydia trachomatis, Mycoplasma genitalium, and Trichomonas vaginalis; bacterial vaginosis (BV)-associated species and genera such as Atopobium vaginae, Sneathia, and Megasphaera; and genera and species usually associated with the gastrointestinal or respiratory tracts such as Bacteroides, Escherichia coli, Streptococcus, or Haemophilus influenza. Although PID is often considered to be synonymous with gonorrhea or chlamydia, these pathogens are found in only one quarter to one third of people with PID, suggesting that broader screening and diagnostic and treatment strategies need to be considered to reduce the burden of PID and its associated sequelae.

Comparison of the Vaginal Microbiota in Postmenopausal Black and White Women.

BACKGROUND: We compared vaginal microbial communities in postmenopausal black and white women. METHODS: Shotgun sequencing of vaginal swabs from postmenopausal women self-identified as black or white was compared using MiRKAT. RESULTS: Vaginal community dominance by Lactobacillus crispatus or Lactobacillusgasseri was more common in 44 postmenopausal black women (n = 12, 27%) than among 44 matched white women (n = 2, 5%; P = .01). No individual taxa were significantly more abundant in either group. CONCLUSIONS: We identified small overall differences in vaginal microbial communities of black and white postmenopausal women. L. crispatus dominance was more common in black women. CLINICAL TRIALS REGISTRATION: NCT02516202 (MsFLASH05) and NCT01418209 (MsFLASH03).

Bacterial Communities Associated With Abnormal Nugent Score in Postmenopausal Versus Premenopausal Women.

The Nugent score is the reference standard for bacterial vaginosis (BV) diagnosis but has not been validated in postmenopausal women. We compared relative abundances from 16S ribosomal RNA gene sequencing of vaginal microbiota with Nugent score in cohorts of premenopausal (n = 220) and postmenopausal (n = 144) women. In premenopausal women, 33 taxa were significantly correlated with Nugent score, including the classic BV-associated taxa Gardnerella, Atopobium, Sneathia, Megasphaera, and Prevotella. In postmenopausal women, 11 taxa were significantly associated with Nugent score, including Prevotella but no other BV-associated genera. High Nugent scores should not be used to infer BV in postmenopausal women.

Association between postmenopausal vulvovaginal discomfort, vaginal microbiota, and mucosal inflammation.

BACKGROUND: Half of all postmenopausal women report symptoms of vulvar, vaginal, or urinary discomfort with substantial impact on sexual function and quality of life; underlying mechanisms leading to symptoms are poorly understood. OBJECTIVE: To examine the possibility that the vaginal microbiota and/or mucosal immune response contributes to the severity of bothersome vaginal symptoms, we conducted a substudy of samples from a randomized trial of vaginal treatment for genitourinary syndrome of menopause to compare these features between women whose symptoms improved and women whose symptoms did not improve. STUDY DESIGN: This is a secondary analysis of samples collected in a 12-week randomized trial of treatment with vaginal estradiol or moisturizer vs placebo for moderate-severe postmenopausal symptoms of vaginal discomfort. We randomly selected 20 women in each arm with ≥2-point decrease in most bothersome symptom severity (responders) and 20 matched controls with ≤1-point decrease (nonresponders). At 0, 4, and 12 weeks, we characterized vaginal microbiota (16S ribosomal RNA gene sequencing), vaginal fluid metabolites (broad-based metabolomic profiling), vaginal fluid-soluble immune markers (Meso Scale Discovery), pH, and vaginal maturation index. We compared responders with nonresponders at baseline and across all visits using linear mixed models to evaluate associations with microbiota, metabolites, and immune markers, incorporating visit and participant-specific random effects while controlling for treatment arm. RESULTS: Here, the mean age of women was 61 years (n=120), and most women (92%) were White. At enrollment, no significant differences were observed between responders and nonresponders in age, most bothersome symptom type or severity, microbiota composition or diversity, Lactobacillus dominance, metabolome, or immune markers. There was a significant decrease in diversity of the vaginal microbiota in both responders and nonresponders (P<.001) over 12 weeks. Although this change did not differ by responder status, diversity was associated with treatment arm: more women in the estradiol arm (63%) had Lactobacillus-dominant, lower diversity bacterial communities than women in the moisturizer (35%) or dual placebo (23%) arms (P=.001) at 12 weeks. The metabolome, vaginal maturation index, and measured immune markers were not associated with responder status over the 12 weeks but varied by treatment arm. CONCLUSION: Postmenopausal vaginal symptom severity was not significantly associated with vaginal microbiota or mucosal inflammatory markers in this small study. Women receiving vaginal estradiol experienced greater abundance of lactobacilli and lower vaginal pH at end of treatment.

Vulvovaginal manifestations in Stevens-Johnson syndrome and toxic epidermal necrolysis: Prevention and treatment.

The prevalence of acute vulvovaginal involvement in toxic epidermal necrolysis can be as high as 70%; up to 28% of female patients will also develop chronic vulvovaginal sequelae. There is little consensus regarding prevention and treatment of the gynecologic sequelae of both Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN). We review acute and chronic sequelae, including erosions, scar formation, chronic skin changes, urethral complications, adenosis, malignant transformation, vulvodynia, and dyspareunia. We provide comprehensive recommendations for acute and long-term vulvovaginal care in adult and pediatric SJS/TEN patients. Treatment should include an ultrapotent topical steroid, followed by a nonirritating barrier cream applied to vulvar and perineal lesions. A steroid should be used intravaginally along with vaginal dilation in all adults (but should be avoided in prepubertal adolescents) with vaginal involvement. Menstrual suppression should be considered in all reproductive age patients until vulvovaginal lesions have healed. Last, referrals for pelvic floor physical therapy and to surgical subspecialties should be offered on a case-by-case basis. This guide summarizes the current available literature combined with expert opinion of both dermatologists and gynecologists who treat a high volume of SJS/TEN patients.

Inflammatory vaginitis in women on long-term rituximab treatment for autoimmune disorders.

BACKGROUND: Consequences of long-term B cell depletion with rituximab are not well understood. We describe inflammatory vaginitis as a potential side effect of long-term rituximab treatment, distinct from previously described vulvovaginal pyoderma gangrenosum. METHODS: We performed a retrospective analysis of women treated with rituximab for more than 1 year to determine the prevalence and clinical characteristics of vaginitis cases. We conducted a case-control analysis with up to 3 controls for each vaginitis case. RESULTS: We identified sixteen inflammatory vaginitis cases. Women with vaginitis were age 23-68 (median 42), primarily being treated for ANCA-associated vasculitis (11/16; 69%). Most reported copious vaginal discharge (100%) and pain with sex (75%). All women with return of circulating B-cells to > 10 cells/mL had complete (5/9) or significant (4/9) improvement in symptoms. In case-control analysis there was no significant difference in length of B-cell depletion, immune parameters, creatinine levels, and history of neutropenia. CONCLUSION: Inflammatory vaginitis is a potential side effect of prolonged continuous B cell depletion with rituximab. More studies are needed to characterize the incidence and etiology of vaginitis among women on long term rituximab therapy and establish a causal relationship.

Association Between Vulvovaginal Discomfort and Activity of Inflammatory Bowel Diseases.

BACKGROUND & AIMS: Inflammatory bowel diseases (IBD) affect 200-400 people per 100,000 in the United States, about half of whom are women. We aimed to define the prevalence of vulvovaginal symptoms and association with IBD activity in a large cohort of women. METHODS: Women more than 18 years old with IBD (1250) completed an online survey querying the presence and severity of vulvar or vaginal itch, burn, or irritation, vaginal discharge or dryness, and vulvovaginal pain. The survey collected information on demographic features and IBD activity (categorized using the Manitoba index). Women with and without symptoms were compared using bivariate analyses. Logistic regression evaluated associations between IBD severity and vulvovaginal symptoms, adjusted for diagnosis, menopause, smoking, depression, and use of medications to treat IBD. RESULTS: A total of 512 (41%) women reported at least 1 moderate-severe vulvovaginal symptom. All vulvovaginal symptoms except vaginal dryness were more common in women with active IBD. In a multivariate model controlled for menopause, smoking, t-score from the PROMIS depression instrument, and use of IBD medications, women with constant or frequent active IBD, based on Manitoba index scores, had increased odds for moderate-severe vulvovaginal symptoms (odds ratio, 1.68; 95% CI, 1.22-2.32) compared to women in remission. Vulvovaginal discomfort frequently or always decreased interest in sex (n=336; 28%) or ability to have sex (n=207; 16%). CONCLUSIONS: In an online survey of 1250 women, we found that women with more active IBD have increased prevalence of vulvovaginal discomfort, compared to women in remission. These symptoms affect sexual health.

Vaginal Microbiota and Mucosal Immune Markers in Women With Vulvovaginal Discomfort.

BACKGROUND: Up to 30% of women with vaginal symptoms are not assigned a diagnosis after standard diagnostic assessment. METHODS: We compared premenopausal women with idiopathic vaginitis (IV) or vulvodynia (VVD) to healthy controls. Microbiota were characterized using rRNA sequencing. Cytokines/chemokines (IL-10, IL-1α, IL-1ß, IL-6, IL-8, IL-2, IL-18, IL-4, IL-9, and IL-13) were measured in vaginal lavage fluid using the Meso Scale Discovery platform or ELISA (IL-1ra). Immunoglobulins were measured in vaginal lavage fluid using a bead-based immunoassay (Millipore). Cases and controls were compared using Kruskal-Wallis, analysis of variance, and linear regression or (for microbiome composition) the Bray-Curtis dissimilarity statistic. RESULTS: We compared 20 women with IV, 30 with VVD, and 52 controls. Most (80%) had greater than 90% 16S rRNA gene sequences from Lactobacillus crispatus, L. jensenii, L. gasseri, or L. iners. In analyses adjusted for age and hormonal contraception (HC), Gardnerella vaginalis was less prevalent and abundant in women with VVD (2/30, 7%) versus controls (16/52, 31%) or IV (5/20, 25%) (P = 0.030). Bray-Curtis dissimilarity was not significantly different between IV and controls or VVD. Fungal sequences were only detected in 5 participants: 2 control, 1 IV, 2 VVD. In univariate analysis, cytokines were not associated with diagnosis. Median vaginal concentration of IgE (but not other immunoglobulins) was lower in women with VVD (P = 0.006). CONCLUSIONS: Minimal differences in vaginal microbiota and inflammatory markers between women with IV, VVD or controls suggest no striking association between vaginal bacteria, fungi or inflammation and diagnosis in these women.

Convergent-Divergent Validity and Correlates of the Day-to-Day Impact of Vaginal Aging Domain Scales in the MsFLASH Vaginal Health Trial.

INTRODUCTION: Clinical research and management of postmenopausal vaginal symptoms have been limited by the lack of validated measures for assessing symptom impact. AIM: To evaluate convergent-divergent validity of the Day-to-Day Impact of Vaginal Aging (DIVA) questionnaire among postmenopausal women with moderate-to-severe vulvovaginal symptoms and identify demographic and clinical factors associated with greater symptom impact. METHODS: We examined baseline data from postmenopausal women with moderate-to-severe vulvovaginal itching, pain, irritation, dryness, or pain with intercourse in a randomized trial of vaginal estradiol, moisturizer, or placebo. In addition to completing the DIVA questionnaire, participants rated the severity of their most bothersome vulvovaginal symptom, underwent assessment of vaginal pH and epithelial cytology, and completed other self-report measures including the Female Sexual Function Index (FSFI), Female Sexual Distress Scale (FSDS), and Patient Health Questionnaire-8 for depression (PHQ-8). MAIN OUTCOME MEASURE: The main outcome measures were the unadjusted correlations and multivariable-adjusted associations with 4 DIVA domain scales designed to assess symptom impact on day-to-day activities, sexual functioning, emotional well-being, and body image/self-concept on a scale of 0 to 4. RESULTS: Among 301 women, we detected moderately strong correlations between the DIVA emotional well-being scale and PHQ-8 scores (Pearson correlation coefficient [r] = 0.39) and strong correlations between the DIVA sexual functioning scale and FSFI and FSDS scores (r > 0.50). No significant correlations were detected between any DIVA scales and vaginal pH or epithelial cytology. In adjusted linear-regression analyses, greater vulvovaginal symptom severity was associated with worse DIVA scores for emotional well-being, sexual functioning, and self-concept/body image (average 0.3- to 0.5-point higher DIVA score for each 1-point difference in vulvovaginal symptom severity). Depression symptoms were associated with worse DIVA scores for activities of daily living and emotional well-being (0.2- to 0.4-point higher DIVA score for each 5- point worsening of PHQ-8 score). Women reporting recent sexual activity had lower symptom impact on sexual functioning and self-concept/body image domains (-0.3- to -0.4-point lower DIVA score with weekly sexual activity). CLINICAL IMPLICATIONS: Findings suggest that the impact of postmenopausal vaginal symptoms on functioning and well-being is greater in women with co-morbid depression symptoms and less frequent sexual activity, independent of symptom severity. STRENGTHS & LIMITATIONS: Strengths include the multicenter sample and wide array of measures. Results may not generalize to women with mild symptoms. CONCLUSION: Our results support the construct validity of the DIVA questionnaire for clinical practice and research and indicate that depression and lower frequency of sexual activity are markers of greater impact of postmenopausal vaginal symptoms on multiple dimensions of functioning and quality of life. Hunter MM, Guthrie KA, Larson JC, et al. Convergent-Divergent Validity and Correlates of the Day-to-Day Impact of Vaginal Aging Domain Scales in the MsFLASH Vaginal Health Trial. J Sex Med 2020;17:117-125.

Generalized Hotelling's test for paired compositional data with application to human microbiome studies.

The human microbiome is a dynamic system that changes due to diseases, medication, change in diet, etc. The paired design is a common approach to evaluate the microbial changes while controlling for the inherent differences between people. For example, microbiome data may be collected from the same individuals before and after a treatment. Two challenges exist in analyzing this type of data. First, microbiome data are compositional such that the reads for all taxa in each sample are constrained to sum to a constant. Second, the number of taxa can be much larger than the sample size. Few statistical methods exist to analyze such data besides methods that test one taxon at a time. In this paper, we propose to first conduct a log-ratio transformation of the compositions, and then develop a generalized Hotelling's test (GHT) to evaluate whether the average microbiome compositions are equivalent in the paired samples. We replace the sample covariance matrix in standard Hotelling's statistic by a shrinkage-based covariance, calculated as a weighted average of the sample covariance and a positive definite target matrix. The optimal weighting can be obtained for many commonly used target matrices. We develop a permutation procedure to assess the statistical significance. Extensive simulations show that our proposed method has well-controlled type I error and better power than a few ad hoc approaches. We apply our method to examine the vaginal microbiome changes in response to treatments for menopausal hot flashes. An R package " GHT" is freely available at https://github.com/zhaoni153/GHT.

Vulvovaginal Discomfort Is Common in Both Premenopausal and Postmenopausal Women.

OBJECTIVES: We surveyed women from a primary care population to assess the prevalence of unreported vulvovaginal symptoms. MATERIALS AND METHODS: A random sample of women aged 18 to 84 years without a diagnosis of vulvovaginitis or vulvodynia in the past year were surveyed anonymously about prevalence and severity of vulvar and vaginal symptoms of itching, burning, irritation, vaginal discharge, vaginal dryness, and vulvovaginal pain in the past month. Women reporting at least 1 moderate-severe symptom were considered symptomatic. Demographic and clinical characteristics were compared between women with and without symptoms using Pearson's χ and Student's t test. RESULTS: Of 1,676 mailed surveys, 272 (16.2%) were returned. Respondents were primarily non-Hispanic (254, 93.4%), White (214, 78.7%), and English speaking (267, 98.2%). More than a third of women (107, 39.3%) reported 1 or more moderate-severe symptoms. Symptomatic women were younger (49 ± 14 years vs 54 ± 15 years, p = .004) and more likely to report a history of asthma (22% vs 12%, p = .028), eczema or seasonal allergies (56% vs 40%, p = .011), or a previous diagnosis of bacterial vaginosis or yeast (36% vs 15%, p < .001) than asymptomatic women. Premenopausal versus postmenopausal women reported similar prevalence of moderate-severe symptoms: 57/136 (42%) vs 50/136 (37%), respectively (p = .39). Symptoms frequently or always interfered with both interest in sex (33/107, 31%) and ability to have sex (32/107, 30%). CONCLUSIONS: This study suggests that moderate-severe vulvovaginal symptoms are prevalent in both premenopausal and postmenopausal women and that these symptoms have a significant impact on sexual health.

The Interplay of Host Immunity, Environment and the Risk of Bacterial Vaginosis and Associated Reproductive Health Outcomes.

Bacterial vaginosis (BV) is one of the most common causes of vaginal symptoms in US women, but its causal mechanism has not yet been defined. BV is more prevalent in women who are immunosuppressed, and several risk factors for the development of BV are associated with lower quantities of immune mediators in vaginal fluid. In contrast, the poor reproductive health outcomes associated with BV, such as preterm birth and human immunodeficiency virus type 1 acquisition, are associated with increased levels of proinflammatory immune mediators in the genital tract. In this article, we discuss how variations in the host immune profile and environmental effects on host immunity may influence the risk of BV, as well as the risk of complications associated with BV.

High Prevalence of Sexual Dysfunction in a Vulvovaginal Specialty Clinic.

OBJECTIVE: Our study evaluated the presence and predictors of sexual dysfunction in a vulvovaginal specialty clinic population. MATERIALS AND METHODS: Women who presented to a vulvovaginal specialty clinic were eligible to enroll. The participants completed a questionnaire, including Female Sexual Function Index to assess sexual dysfunction and Patient Health Questionnaire (PHQ)-9 depression screen, and underwent a standardized physical examination, with vaginal swabs collected for wet mount and culture. Logistic regression assessed the relationship between sexual dysfunction and clinical diagnosis. RESULTS: We enrolled 161 women, aged 18 to 80 years (median, 36 years), presenting with vulvovaginal complaints. Median symptom duration was 24 months; 131 women (81%) reported chronic symptoms (≥12 months). By PHQ-9, 28 women (17%) met depression criteria. In the month before assessment, 86 women (53%) experienced sexual dysfunction. Women had a primary diagnosis of vaginitis (n = 46 [29%]), vestibulodynia/vulvitis (n = 70 [43%]), lichen planus or lichen sclerosus (n = 24 [15%]). Controlling for age, we found that sexual dysfunction did not correlate with chronic symptoms (incidence rate ratio [IRR], 0.86; 95% confidence interval [CI], 0.50-1.48), depression (IRR, 1.24; 95% CI, 0.59-2.58), or presence of any of the 3 main diagnoses (IRR, 1.16; 95% CI, 0.47-2.88). DISCUSSION: Sexual dysfunction is present in more than half of women presenting to a vulvovaginitis referral clinic, more than twice the rate in the wider population.

Colonization of the upper genital tract by vaginal bacterial species in nonpregnant women.

OBJECTIVE: The objective of the study was to evaluate the upper genital tract (UGT) presence of vaginal bacterial species using sensitive molecular methods capable of detecting fastidious bacterial vaginosis (BV)-associated bacteria. STUDY DESIGN: Vaginal swabs were collected prior to hysterectomy. The excised uterus was sterilely opened and swabs collected from the endometrium and upper endocervix. DNA was tested in 11 quantitative polymerase chain reaction (PCR) assays for 12 bacterial species: Lactobacillus iners, L crispatus, L jensenii, Gardnerella vaginalis, Atopobium vaginae, Megasphaera spp, Prevotella spp, Leptotrichia/Sneathia, BVAB1, BVAB2, BVAB3, and a broad-range16S ribosomal ribonucleic acid gene assay. Endometrial fluid was tested with Luminex and an enzyme-linked immunosorbent assay for cytokines and defensins and tissue for gene expression of defensins and cathelicidin. RESULTS: We enrolled 58 women: mean aged 43±7 years, mostly white (n=46; 79%) and BV negative (n=43; 74%). By species-specific quantitative PCR, 55 (95%) had UGT colonization with at least 1 species (n=52) or were positive by 16S PCR (n=3). The most common species were L iners (45% UGT, 61% vagina), Prevotella spp (33% UGT, 76% vagina) and L crispatus (33% UGT, 56% vagina). Median quantities of bacteria in the UGT were lower than vaginal levels by 2-4 log10 ribosomal ribonucleic acid gene copies per swab. There were no differences in the endometrial inflammatory markers between women with no bacteria, Lactobacillus only, or any BV-associated species in the UGT. CONCLUSION: Our data suggest that the endometrial cavity is not sterile in most women undergoing hysterectomy and that the presence of low levels of bacteria in the uterus is not associated with significant inflammation.

Long-term effect of depot medroxyprogesterone acetate on vaginal microbiota, epithelial thickness and HIV target cells.

BACKGROUND: Depot medroxyprogesterone acetate (DMPA) has been linked to human immunodeficiency virus type 1 (HIV-1) acquisition. METHODS: Vaginal microbiota of women using DMPA for up to 2 years were cultured. Mucosal immune cell populations were measured by immunohistological staining. RESULTS: Over 12 months, the proportion with H2O2-positive lactobacilli decreased (n = 32; 53% vs 27%; P = .03). Median vaginal CD3(+) cells also decreased (n = 15; 355 vs 237 cells/mm(2); P = .03), as did CD3(+)CCR5(+) cells (195 vs 128 cells/mm(2); P = .04), HLA-DR(+) cells (130 vs 96 cells/mm(2); P = .27), and HLA-DR(+)CCR5(+) cells (18 vs 10 cells/mm(2); P = .33). CONCLUSIONS: DMPA contraception does not increase vaginal mucosal CCR5(+) HIV target cells but does decrease CD3(+) T lymphocytes and vaginal H2O2-producing lactobacilli.

Association between vaginal microbiota and vaginal inflammatory immune markers in postmenopausal women.

OBJECTIVE: In premenopausal individuals, vaginal microbiota diversity and lack of Lactobacillus dominance are associated with greater mucosal inflammation, which is linked to a higher risk of cervical dysplasia and infections. It is not known if the association between the vaginal microbiota and inflammation is present after menopause, when the vaginal microbiota is generally higher-diversity and fewer people have Lactobacillus dominance. METHODS: This is a post hoc analysis of a subset of postmenopausal individuals enrolled in a randomized trial for treatment of moderate-severe vulvovaginal discomfort that compared vaginal moisturizer, estradiol, or placebo. Vaginal fluid samples from 0, 4, and 12 weeks were characterized using 16S rRNA gene sequencing (microbiota) and MesoScale Discovery (vaginal fluid immune markers: IL-1b, IL-1a, IL-2, IL-6, IL-18, IL-10, IL-9, IL-13, IL-8, IP10, MIP1a, MIP1b, MIP3a). Global associations between cytokines and microbiota (assessed by relative abundance of individual taxa and Shannon index for alpha, or community, diversity) were explored, adjusting for treatment arm, using linear mixed models, principal component analysis, and Generalized Linear Mixed Model + Microbiome Regression-based Kernel Association Test (GLMM-MiRKAT). RESULTS: A total of 119 individuals with mean age of 61 years were included. At baseline, 29.5% of participants had a Lactobacillus-dominant vaginal microbiota. Across all timepoints, alpha diversity (Shannon index, P = 0.003) was highly associated with immune markers. Individual markers that were associated with Lactobacillus dominance were similar to those observed in premenopausal people: IL-10, IL-1b, IL-6, IL-8 (false discovery rate [FDR] < 0.01), IL-13 (FDR = 0.02), and IL-2 (FDR = 0.09). Over 12 weeks, change in alpha diversity was associated with change in cytokine concentration (Shannon, P = 0.018), with decreased proinflammatory cytokine concentrations observed with decreasing alpha diversity. CONCLUSIONS: In this cohort of postmenopausal individuals, Lactobacillus dominance and lower alpha diversity were associated with lower concentrations of inflammatory immune markers, as has been reported in premenopausal people. This suggests that after menopause lactobacilli continue to have beneficial effects on vaginal immune homeostasis, despite lower prevalence.

Recommended measurement instruments for genitourinary symptoms associated with menopause: the COMMA (Core outcomes in menopause) consortium.

OBJECTIVE: The aim of the study is to identify appropriate definitions and patient-reported outcome measures (PROMs) for each of the eight core outcomes previously selected for genitourinary symptoms associated with menopause: pain with sex, vulvovaginal dryness, vulvovaginal discomfort or irritation, discomfort or pain when urinating, change in most bothersome symptom, distress, bother or interference of genitourinary symptoms, satisfaction with treatment, and side effects. METHODS: We conducted a systematic review to identify possible definitions and PROMs, including their measurement properties. Identified definitions and relevant PROMs with acceptable measurement properties were entered into an international consensus process involving 28 participants from 10 countries to achieve final recommendations for each core outcome. RESULTS: A total of 87 publications reporting on 34 PROMs were identified from 21,207 publications screened. Of these 34 PROMs, 29 were not considered to sufficiently map onto the core outcomes, and 26 of these also had insufficient measurement properties. Therefore, only five PROMs corresponding to two core outcomes were considered for recommendation. We recommend the PROMIS Scale v2.0 - Sexual Function and Satisfaction: Vaginal Discomfort with Sexual Activity to measure the outcome of "pain with sexual activity" and the Day-to-Day Impact of Vaginal Aging (DIVA) Questionnaire to measure "distress, bother or interference" from genitourinary symptoms. Six definitions of "side effects" were identified and considered. We recommend that all trials report adverse events in study participants, which is a requirement of Good Clinical Practice. CONCLUSIONS: Suitable PROMs and definitions were identified to measure three of eight core outcomes. Because of the lack of existing measures, which align with the core outcomes and have evidence of high-quality measurement properties, future work will focus on developing or validating PROMs for the remaining five core outcomes.

Bacterial vaginosis: a review of approaches to treatment and prevention.

Bacterial vaginosis (BV) is a common cause of vaginitis worldwide and is associated with serious reproductive health outcomes, including increased risk of preterm birth, sexually transmitted infections, and pelvic inflammatory disease. The current and only FDA-approved treatment regimens for BV are antibiotics, such as metronidazole and clindamycin. Antibiotics provide a short-term cure for bacterial vaginosis; however, fail to provide a consistent long-term cure for many women. Fifty to eighty percent of women experience a BV recurrence within a year of completing antibiotic treatment. This may be because after antibiotic treatment, beneficial strains of Lactobacillus, such as L. crispatus, do not recolonize the vagina. In the absence of an effective long-term cure, patients, providers, and researchers are exploring different approaches to treatment and prevention, resulting in a rapid evolution of perspectives on BV pathogenesis and approaches to management. Current areas of investigation for BV management include probiotics, vaginal microbiome transplantation, pH modulation, and biofilm disruption. Behavioral modifications that may help include smoking cessation, condom use and hormonal contraception. Additional strategies considered by many people include dietary modification, non-medical vaginally applied products, choice of lubricant, and treatments from medical practices outside of allopathic medicine. This review aims to provide a comprehensive and up to date outline of the landscape of ongoing and potential treatment and prevention strategies for BV.

The vagina question: Can maternal vaginal fluid impact the infant gut microbiome and neurodevelopment?

Cesarean section rates continue to rise globally, and C-sectioned infants are at a higher risk of adverse child outcomes. In this issue of Cell Host & Microbe, Zhou et al. report that vaginal microbial transfer (VMT) from birth mother to infant post-delivery may alter infant gut microbiota and improve neurodevelopment.