Urinary microbiome community types associated with urinary incontinence severity in women

American Journal of Obstetrics and Gynecology

Published On 2024/3/1

BackgroundUrinary microbiome (urobiome) studies have previously reported on specific taxa and community differences in women with mixed urinary incontinence compared with controls. Therefore, a hypothesis was made that higher urinary and vaginal microbiome diversity would be associated with increased urinary incontinence severity.ObjectiveThis study aimed to test whether specific urinary or vaginal microbiome community types are associated with urinary incontinence severity in a population of women with mixed urinary incontinence.Study DesignThis planned secondary, cross-sectional analysis evaluated associations between the urinary and vaginal microbiomes and urinary incontinence severity in a subset of Effects of Surgical Treatment Enhanced With Exercise for Mixed Urinary Incontinence trial participants with urinary incontinence. Incontinence severity was measured using bladder diaries and …

Journal

American Journal of Obstetrics and Gynecology

Volume

230

Issue

3

Page

344. e1-344. e20

Authors

Linda Brubaker

Linda Brubaker

University of California, San Diego

H-Index

87

Research Interests

urobiome

recurrent UTI

urinary incontinence

prolapse

Nazema Siddiqui

Nazema Siddiqui

Duke University

H-Index

33

Research Interests

University Profile Page

Darrell L. Dinwiddie

Darrell L. Dinwiddie

University of New Mexico

H-Index

26

Research Interests

Genomics

Immunology

Infectious Diseases

University Profile Page

Other Articles from authors

Linda Brubaker

Linda Brubaker

University of California, San Diego

Microbiology Spectrum

Effects of variation in sample storage conditions and swab order on 16S vaginal microbiome analyses

Technical bias is a pressing issue in microbiome research, and variability can be introduced at any stage from sample collection to figure generation. In this study, we aim to reduce biases in studying the human vaginal microbiome by examining the impact of sample storage buffer and multiple swabbing events using 16S rRNA gene amplicon sequencing data generated from vaginal swabs. We show that AssayAssure Genelock, a clinically relevant preservative for urine samples, is effective in preserving vaginal samples for microbiome studies. When comparing Genelock to 95% (vol/vol) ethanol and no preservative (air only), host variability explained more variance in both weighted and unweighted UniFrac measurements than the preservation method. We further examined the impact of three successive self-swabbing events, as the relatively low biomass nature of vaginal samples can inherently introduce bias. It …

Nazema Siddiqui

Nazema Siddiqui

Duke University

BJOG: An International Journal of Obstetrics & Gynaecology

Vaginal morphology and position associated with prolapse recurrence after vaginal surgery: a secondary analysis of the DEMAND study

Objective To identify vaginal morphology and position factors associated with prolapse recurrence following vaginal surgery. Design Secondary analysis of magnetic resonance images (MRI) of the Defining Mechanisms of Anterior Vaginal Wall Descent cross‐sectional study. Setting Eight clinical sites in the US Pelvic Floor Disorders Network. Population or Sample Women who underwent vaginal mesh hysteropexy (hysteropexy) with sacrospinous fixation or vaginal hysterectomy with uterosacral ligament suspension (hysterectomy) for uterovaginal prolapse between April 2013 and February 2015. Methods The MRI (rest, strain) obtained 30–42 months after surgery, or earlier for participants with recurrence who desired reoperation before 30 months, were analysed. MRI‐based prolapse recurrence was defined as prolapse beyond the hymen at strain on MRI. Vaginal segmentations (at rest) were used to …

Linda Brubaker

Linda Brubaker

University of California, San Diego

bioRxiv

Urinary Metabolomic Profile is Minimally Impacted by Common Storage Conditions and Additives

Metabolomics reflects the molecular communications within a biological system. Urine can be obtained non-invasively and is rich in metabolites that are potential biomarkers for human health and disease. The optimal urine storage conditions for metabolomic analysis are unknown. We measured the impact of common storage conditions and the presence of a DNA-stabilizer, AssayAssure® (Thermo Scientific), on metabolite content of voided human urine. Urinary metabolite composition was not altered across storage conditions. Although addition of AssayAssure® significantly alters metabolic profile by adduct addition, this does not preclude the identification of parent metabolites or overshadow biological differences. These data suggest biobanked urine stored in any of the tested conditions for metabolomic studies may be considered for metabolomic analysis.

Linda Brubaker

Linda Brubaker

University of California, San Diego

Accountability in Research

A policy toolkit for authorship and dissemination policies may benefit NIH research consortia

Authorship and dissemination policies vary across NIH research consortia. We aimed to describe elements of real-life policies in use by eligible U01 clinical research consortia. Principal investigators of eligible, active U01 clinical research projects identified in the NIH Research Portfolio Online Reporting Tools database shared relevant policies. The characteristics of key policy elements, determined a priori, were reviewed and quantified, when appropriate. Twenty one of 81 research projects met search criteria and provided policies. K elements (e.g., in quotations): “manuscript proposals reviewed and approved by committee” (90%); “guidelines for acknowledgements” (86%); “writing team formation” (71%); “process for final manuscript review and approval” (71%), “responsibilities for lead author” (67%), “guidelines for other types of publications” (67%); “draft manuscript review and approval” (62 …

Darrell L. Dinwiddie

Darrell L. Dinwiddie

University of New Mexico

npj Viruses

Genome sequencing identifies “Limestone Canyon virus” as Montaño virus (Hantaviridae: Orthohantavirus montanoense) circulating in brush deermice in New …

Orthohantaviruses infect distinct eulipotyphlan and rodent reservoirs throughout the world; some rodent orthohantaviruses can cause disease in humans. In the United States, a primary rodent reservoir for the human-pathogenic Sin Nombre virus (SNV) is the western deermouse (Peromyscus sonoriensis; formerly included in Peromyscus maniculatus). Deermice (rodents of genus Peromyscus) carry presumably distinct orthohantaviruses but, although deermice of ten species have been recorded in New Mexico, only SNV has been reported in rodents from that state. Using a set of pan-orthohantavirus primers, we discovered a non-SNV orthohantavirus in a brush deermouse (P. boylii), trapped in central New Mexico in 2019. Sequencing enabled the generation of a consensus coding-complete genome sequence, revealing similarity to the known partial sequences of the unclassified “Limestone Canyon virus (LSCV …

Linda Brubaker

Linda Brubaker

University of California, San Diego

Introducing At the Scrub Sink!

This new journal feature is intended to stimulate a thoughtful preparation for surgeons preparing their hands to treat patients. Preparing both mind and body is an age-old ritual–one very familiar to all surgeons. The Urogynecology Assistant Editors have developed a (pretty large!) list of potential topics for this feature. We welcome additional suggestions for this new feature! If you have a suggestion for the Assistant Editors, please send it to us at Editor@ urogynjournal. org.

Nazema Siddiqui

Nazema Siddiqui

Duke University

Journal of Urology

Proposing the “Continuum of Urinary Tract Infection (UTI)” for a Nuanced Approach to Diagnosis and Management of UTIs

Purpose:Patients with suspected urinary tract infections (UTIs) are categorized into three clinical phenotypes based on current guidelines: no UTI, asymptomatic bacteriuria (ASB), or UTI. However, all patients may not fit neatly into these groups. Our objective was to characterize clinical presentations of patients who receive urine tests using the “continuum of UTI” approach.Materials and Methods:This was a retrospective cohort study of a random sample of adult non-catheterized inpatient and ED encounters with paired urinalysis and urine cultures from 5 hospitals in three states between January 01, 2017 and December 31, 2019. Trained abstractors collected clinical (eg, symptom) and demographic data. A focus group discussion with multidisciplinary experts was conducted to define the “continuum of UTI,” a 5-level classification scheme that includes two new categories: lower urinary tract symptoms/other urologic …

Linda Brubaker

Linda Brubaker

University of California, San Diego

Harnessing the power within: engineering the microbiome for enhanced gynecologic health

Although numerous studies have demonstrated the impact of microbiome manipulation on human health, research on the microbiome’s influence on female health remains relatively limited despite substantial disease burden. In light of this, we present a selected review of clinical trials and preclinical studies targeting both the vaginal and gut microbiomes for the prevention or treatment of various gynecologic conditions. Specifically, we explore studies that leverage microbiota transplants, probiotics, prebiotics, diet modifications, and engineered microbial strains. A healthy vaginal microbiome for females of reproductive age consists of lactic acid-producing bacteria predominantly of the Lactobacillus genus, which serves as a protective barrier against pathogens and maintains a balanced ecosystem. The gut microbiota’s production of short-chain fatty acids, metabolism of primary bile acids, and modulation of sex …

Linda Brubaker

Linda Brubaker

University of California, San Diego

Journal of Wound Ostomy & Continence Nursing

Association between maternal depression and lower urinary tract symptoms in their primary school-age daughters: A birth cohort study

PURPOSE:Although maternal depression is associated with adverse outcomes in women and children, its relationship with lower urinary tract symptoms (LUTS) in offspring is less well-characterized. We examined the association between prenatal and postpartum maternal depression and LUTS in primary school-age daughters.DESIGN:Observational cohort study.SUBJECTS AND SETTING:The sample comprised 7148 mother-daughter dyads from the Avon Longitudinal Study of Parents and Children.METHOD:Mothers completed questionnaires about depressive symptoms at 18 and 32 weeks' gestation and 21 months postpartum and their children's LUTS (urinary urgency, nocturia, and daytime and nighttime wetting) at 6, 7, and 9 years of age. Multivariable logistic regression models were used to estimate the association between maternal depression and LUTS in daughters.RESULTS:Compared to daughters of …

Nazema Siddiqui

Nazema Siddiqui

Duke University

bioRxiv

Commensal bacteria inhibit viral infections via a tryptophan metabolite

There is growing appreciation that commensal bacteria impact the outcome of viral infections, though the specific bacteria and their underlying mechanisms remain poorly understood. Studying a simian-human immunodeficiency virus (SHIV)-challenged cohort of pediatric nonhuman primates, we bioinformatically associated Lactobacillus gasseri and the bacterial family Lachnospiraceae with enhanced resistance to infection. We experimentally validated these findings by demonstrating two different Lachnospiraceae isolates, Clostridium immunis and Ruminococcus gnavus, inhibited HIV replication in vitro and ex vivo. Given the link between tryptophan catabolism and HIV disease severity, we found that an isogenic mutant of C. immunis that lacks the aromatic amino acid aminotransferase (ArAT) gene, which is key to metabolizing tryptophan into 3-indolelactic acid (ILA), no longer inhibits HIV infection. Intriguingly, we confirmed that a second commensal bacterium also inhibited HIV in an ArAT-dependent manner, thus establishing the generalizability of this finding. In addition, we found that purified ILA inhibited HIV infection by agonizing the aryl hydrocarbon receptor (AhR). Given that the AhR has been implicated in the control of multiple viral infections, we demonstrated that C. immunis also inhibited human cytomegalovirus (HCMV) infection in an ArAT-dependent manner. Importantly, metagenomic analysis of individuals at-risk for HIV revealed that those who ultimately acquired HIV had a lower fecal abundance of the bacterial ArAT gene compared to individuals who did not, which indicates our findings translate to humans. Taken together, our …

Darrell L. Dinwiddie

Darrell L. Dinwiddie

University of New Mexico

PLOS Neglected Tropical Diseases

Choclo virus (CHOV) recovered from deep metatranscriptomics of archived frozen tissues in natural history biorepositories

Background Hantaviruses are negative-stranded RNA viruses that can sometimes cause severe disease in humans; however, they are maintained in mammalian host populations without causing harm. In Panama, sigmodontine rodents serve as hosts to transmissible hantaviruses. Due to natural and anthropogenic forces, these rodent populations are having increased contact with humans. Methods We extracted RNA and performed Illumina deep metatranscriptomic sequencing on Orthohantavirus seropositive museum tissues from rodents. We acquired sequence reads mapping to Choclo virus (CHOV, Orthohantavirus chocloense) from heart and kidney tissue of a two-decade old frozen museum sample from a Costa Rican pygmy rice rat (Oligoryzomys costaricensis) collected in Panama. Reads mapped to the CHOV reference were assembled and then validated by visualization of the mapped reads against the assembly. Results We recovered a 91% complete consensus sequence from a reference-guided assembly to CHOV with an average of 16X coverage. The S and M segments used in our phylogenetic analyses were nearly complete (98% and 99%, respectively). There were 1,199 ambiguous base calls of which 93% were present in the L segment. Our assembled genome varied 1.1% from the CHOV reference sequence resulting in eight nonsynonymous mutations. Further analysis of all publicly available partial S segment sequences support a clear relationship between CHOV clinical cases and O. costaricensis acquired strains. Conclusions Viruses occurring at extremely low abundances can be recovered from deep …

Nazema Siddiqui

Nazema Siddiqui

Duke University

Antimicrobial Stewardship & Healthcare Epidemiology

Proposing the “Continuum of UTI” for a Nuanced Approach to Diagnosis and Management of Urinary Tract Infections

Background Historically, diagnosis of urinary tract infections (UTIs) has been divided into 3 categories based on symptoms and urine culture results: not UTI, asymptomatic bacteriuria (ASB), or UTI. However, some populations (eg, older adults, catheterized patients) may not present with signs or symptoms referrable to the urinary tract or have chronic lower urinary tract symptoms (LUTS), making the diagnosis of UTI challenging. We sought to understand the clinical presentation of patients who receive urine tests in a cohort of diverse hospitals. Methods This retrospective descriptive cohort study included all adult noncatheterized inpatient and ED encounters with paired urinalysis and urine cultures (24 hours apart) from 5 community and academic hospitals in 3 states (NC, VA, GA) between January 1, 2017, and December 31, 2019. Trained abstractors collected clinical and demographic data using a 60-question …

Linda Brubaker

Linda Brubaker

University of California, San Diego

Neurourology and Urodynamics

The brain, gut, and bladder health nexus: A conceptual model linking stress and mental health disorders to overactive bladder in women

Objective A small, but growing literature links stressors and mental health disorders (MHDs) across the life course to overactive bladder (OAB) and urinary incontinence symptoms. Mechanisms by which stressors and MHDs may impact bladder health are not fully understood, limiting novel prevention and treatment efforts. Moreover, potential biopsychosocial mechanisms involving the brain and gut have not been considered in an integrated, comprehensive fashion. Methods Members of the prevention of lower urinary tract symptoms Research Consortium developed conceptual models to inform research on biopsychosocial mechanisms through which stress and MDHs may impact bladder health among girls and women, focusing on brain and gut physiology. Results Two conceptual models were developed—one to explain central (brain‐based) and peripheral (gut‐based) mechanisms linking stressors and …

Linda Brubaker

Linda Brubaker

University of California, San Diego

Neurourology and Urodynamics

The RISE FOR HEALTH study: Methods for in‐person assessment and biospecimen collection

Objectives To describe the methods for the in‐person assessment of the RISE FOR HEALTH (RISE) study, a population‐based multicenter prospective cohort study designed to identify factors that promote bladder health and/or prevent lower urinary tract symptoms in adult women, conducted by the Prevention of Lower Urinary Tract Symptoms Research Consortium (PLUS). Methods and results A subset of RISE participants who express interest in the in‐person assessment will be screened to ensure eligibility (planned n = 525). Eligible consenting participants are asked to complete 15 physical assessments in addition to height and weight, to assess pelvic floor muscle function, musculoskeletal (MSK) status, and pain, and to provide urogenital microbiome samples. Pelvic floor muscle assessments include presence of prolapse, strength, levator attachment integrity (tear) and myofascial pain. MSK tests evaluate …

Linda Brubaker

Linda Brubaker

University of California, San Diego

International Urogynecology Journal

Microbiologist in the clinic: coitally related symptoms with negative urine cultures

In this first episode of the Microbiologist in the Clinic series, clinicians and laboratory scientists share their perspectives about a 30 y/o woman, who is seeking specialty consultation for frequent episodes of urinary urgency, frequency, and dysuria, which respond to short courses of antibiotics. Although her home dipsticks suggest that she has a UTI, and her urinalysis typically has a moderate number of white blood cells, her urine cultures are always negative. The challenges of this clinical presentation are discussed with evidence for evaluation and treatment.

Nazema Siddiqui

Nazema Siddiqui

Duke University

Microbiology Resource Announcements

Draft genomes of Lactobacillus delbrueckii and Klebsiella pneumoniae coexisting within a female urinary bladder

Here, we present the draft genome sequences of Lactobacillus delbrueckii and Klebsiella pneumoniae, both isolated from the urinary bladder of an asymptomatic post-menopausal female patient with a diagnosis of recurrent urinary tract infections. These genomes will facilitate analyses of interbacterial interactions in the urinary microbiome.

2023/10/19

Article Details
Darrell L. Dinwiddie

Darrell L. Dinwiddie

University of New Mexico

Genomic Sequencing of an Atypical Outbreak of Human Metapneumovirus in a Pediatric Population Reveals the Co-circulation of Multiple Genetic Lineages

Human metapneumovirus (HMPV) is a common cause of respiratory infections in children, accounting for 5-15% of all acute respiratory infections in this population. Although HMPV is closely related to respiratory syncytial virus (RSV) its incidence, epidemiology, and genetic diversity are poorly understood. In the United States, HMPV infections typically occur annually in the winter and early spring months. Similar to other common respiratory viruses, during the first two years of the COVID-19 pandemic, cases of HMPV were nearly absent. However, in the summer and early fall of 2022 an atypical and dramatic increase of HMPV cases across the United States was detected. In addition to the infections being out of the typical winter respiratory infection season, the incidence and clinical severity appeared to be increased. To investigate if the atypical infections were due to a new and more virulent strain of HMPV, we conducted genomic sequencing of 96 pediatric cases from Arkansas Children’s Research Institute. Genetic analysis revealed the co-circulation of multiple genetic lineages, including two recently described lineages with large duplications in the surface glycoprotein, G; however, no novel mutations or lineages were detected. Our data indicates that the atypical outbreak of HMPV in 2022 was not caused by a new strain of HMPV. It is possible that the increase in cases may have been in response to a decrease in the use of preventive measures such as wearing masks, and social distancing and/or exposure in a population with reduced and waning natural immunity.

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Nazema Siddiqui

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American Journal of Obstetrics and Gynecology

Urinary microbiome community types associated with urinary incontinence severity in women

BackgroundUrinary microbiome (urobiome) studies have previously reported on specific taxa and community differences in women with mixed urinary incontinence compared with controls. Therefore, a hypothesis was made that higher urinary and vaginal microbiome diversity would be associated with increased urinary incontinence severity.ObjectiveThis study aimed to test whether specific urinary or vaginal microbiome community types are associated with urinary incontinence severity in a population of women with mixed urinary incontinence.Study DesignThis planned secondary, cross-sectional analysis evaluated associations between the urinary and vaginal microbiomes and urinary incontinence severity in a subset of Effects of Surgical Treatment Enhanced With Exercise for Mixed Urinary Incontinence trial participants with urinary incontinence. Incontinence severity was measured using bladder diaries and …

helen morgan

helen morgan

University of Michigan-Dearborn

American journal of obstetrics and gynecology

Current practices and perspectives on clerkship grading in obstetrics and gynecology

BackgroundClerkship grades in obstetrics and gynecology play an increasingly important role in the competitive application process to residency programs. An analysis of clerkship grading practices has not been queried in the past 2 decades in our specialty.ObjectiveThis study aimed to investigate obstetrics and gynecology clerkship directors’ practices and perspectives in grading.Study DesignA 12-item electronic survey was developed and distributed to clerkship directors with active memberships in the Association of Professors of Gynecology and Obstetrics.ResultsA total of 174 of 236 clerkship directors responded to the survey (a response rate of 73.7%). Respondents reported various grading systems with the fewest (20/173 [11.6%]) using a 2-tiered or pass or fail system and the most (72/173 [41.6%]) using a 4-tiered system. Nearly one-third of clerkship directors (57/163 [35.0%]) used a National Board of …

Brenna L Hughes

Brenna L Hughes

Duke University

American Journal of Obstetrics and Gynecology

Society for Maternal-Fetal Medicine Statement: Clinical considerations for the prevention of respiratory syncytial virus disease in infants

Respiratory syncytial virus is a leading cause of lower respiratory tract illness globally in children aged <5 years. Each year, approximately 58,000 hospitalizations in the United States are attributed to respiratory syncytial virus. Infants aged ≤6 months experience the most severe morbidity and mortality. Until recently, prevention with the monoclonal antibody, palivizumab, was only offered to infants with high-risk conditions, and treatment primarily consisted of supportive care. Currently, 2 products are approved for the prevention of respiratory syncytial virus in infants. These include the Pfizer bivalent recombinant respiratory syncytial virus prefusion F protein subunit vaccine, administered seasonally to the pregnant person between 32 0/7 and 36 6/7 weeks of gestation, and the monoclonal antibody, nirsevimab, administered to infants aged up to 8 months entering their first respiratory syncytial virus season. With few …

Carolin C. M. Schulte

Carolin C. M. Schulte

University of Oxford

American Journal of Obstetrics and Gynecology

The simultaneous occurrence of gestational diabetes and hypertensive disorders of pregnancy affects fetal growth and neonatal morbidity

BackgroundGestational diabetes (GDM) is associated with an increased risk of hypertensive disorders of pregnancy (HDP), but there are limited data on fetal growth and neonatal outcomes when both conditions are present.ObjectivesWe evaluated the risk of abnormal fetal growth and neonatal morbidity in pregnancies with co-occurrence of GDM and HDP.Study DesignIn a retrospective study of 47,093 singleton pregnancies, we compared the incidence of appropriate for gestational age birthweight (AGA) in pregnancies affected by GDM alone, HDP alone, or both GDM and HDP (GDM/HDP) to that in pregnancies affected by neither disorder using generalized estimating equations (covariates: maternal age, nulliparity, BMI, insurance type, race, marital status and prenatal care site). Secondary outcomes were large for gestational age birthweight (LGA), small for gestational age birthweight (SGA), and a neonatal …

Pauline M. Maki

Pauline M. Maki

University of Illinois at Chicago

American journal of obstetrics and gynecology

Menopausal vasomotor symptoms and plasma Alzheimer disease biomarkers

BackgroundIdentifying risk factors for Alzheimer disease in women is important as women compose two-thirds of individuals with Alzheimer disease. Previous work links vasomotor symptoms, the cardinal menopausal symptom, with poor memory performance and alterations in brain structure, function, and connectivity. These associations are evident when vasomotor symptoms are monitored objectively with ambulatory skin conductance monitors.ObjectiveThis study aimed to determine whether vasomotor symptoms are associated with Alzheimer disease biomarkers.Study DesignBetween 2017 and 2020, the MsBrain study enrolled 274 community-dwelling women aged 45 to 67 years who had a uterus and at least 1 ovary and were late perimenopausal or postmenopausal status. The key exclusion criteria included neurologic disorder, surgical menopause, and recent use of hormonal or nonhormonal vasomotor …

Mukhri Hamdan

Mukhri Hamdan

Universiti Malaya

American Journal of Obstetrics and Gynecology

Preoperative free access to water compared to fasting for planned cesarean under spinal anesthesia: a randomized controlled trial

BackgroundContemporary guidance for preoperative feeding allows solids up to 6 hours and clear fluids up to 2 hours before anesthesia. Clinical trial evidence to support this approach for cesarean delivery is lacking. Many medical practitioners continue to follow conservative policies of no intake from midnight to the time of surgery, especially in pregnant women.ObjectiveThis study aimed to evaluate the pragmatic approach of permitting free access to water up to the call to dispatch to the operating theater vs fasting from midnight in preoperative oral intake restriction for planned cesarean delivery under spinal anesthesia on perioperative vomiting and maternal satisfaction.Study DesignA randomized controlled trial was conducted in the obstetrical unit of the University of Malaya Medical Centre from October 2020 to May 2022. A total of 504 participants scheduled for planned cesarean delivery were randomized …