Vaginal estrogen therapy is associated with increased Lactobacillus in the urine of postmenopausal women with overactive bladder symptoms

Thomas‐White, Krystal; Taege, Susanne; Limeira, Roberto; Brincat, Cynthia; Joyce, Cara; Hilt, Evann E.; Mac-Daniel, Laura; Radek, Katherine A.; Brubaker, Linda; Wolfe, Alan J.

doi:10.1016/j.ajog.2020.08.006

Cited by 52 publications

(55 citation statements)

References 39 publications

(33 reference statements)

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“…There is clear, reproduced evidence that culture-independent or enhanced culture techniques detect more microbes than the standard culture techniques. 17,19,29 However, these techniques still have limitations, including uncharacterized microbes below our detection limit of <10 colony forming units/ml, those not detected by our culture methods (such as non-Candida fungi), or the consequence of intact intracellular bacterial communities not shed into urine. 30 This study is additionally limited to a RUTI population in which other factors of this disease process, including host response and sensitivity, may be different than that of other populations with lower urinary tract symptoms.…”

Section: Discussionmentioning

confidence: 96%

Recurrent urinary tract infection: Association of clinical profiles with urobiome composition in women

Burnett

Hochstedler

Weldon

et al. 2021

Neurourology and Urodynamics

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Aims: Clinical profiles of women with recurrent urinary tract infection (RUTI) are correlated with their urinary microbes. Methods: This IRB-approved, cross-sectional study enrolled adult women with RUTI. Urine samples (catheterized and voided) underwent culture by expanded quantitative urine culture (EQUC) and standard urine culture (SUC) methods. A validated symptom questionnaire, relevant clinical variables, and EQUC were used to identify symptom clusters and detect associations with specific urinary microbes.Results: Most (36/43) participants were postmenopausal; the average age was 67 years. 51% reported vaginal estrogen use; 51% reported sexual activity. Although single symptoms were not associated with specific urinary microbes, EQUC results were correlated with five distinct clinical profile clusters: Group A: odor, cloudiness, and current vaginal estrogen use (no culture result association). Group B: frequency, low back pain, incomplete emptying, and vaginal estrogen (significantly increased proportion of Lactobacillus-positive cultures). Group C: pain/burning, odor, cloudiness, and urgency (high proportions of UTI-associated microbe-positive cultures). Group D: frequency, urgency, pain/burning, and current vaginal estrogen use (increased number of no growth cultures). Group E: frequency, urgency, pain/burning, odor, overactive bladder, and sexually active (significantly increased proportion of Klebsiella-positive cultures).Conclusions: Distinct clinical profiles are associated with specific urinary microbes in women with RUTI. Refined assessments of clinical profiles may provide useful insights that could inform diagnostic and therapeutic considerations.

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Section: Discussionmentioning

confidence: 96%

Recurrent urinary tract infection: Association of clinical profiles with urobiome composition in women

Burnett

Hochstedler

Weldon

et al. 2021

Neurourology and Urodynamics

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“…These signs and symptoms, along with others, define the genitourinary syndrome of menopause (GSM) – a condition which affects approximately half of post-menopausal women ( Portman et al., 2014 ). Because GSM affects both the vaginal microbiota and urinary tract ( Thomas-White et al., 2020 ), and because lower vaginal bacterial loads may affect the ability of RC urine to collect vaginal microbes, we separately evaluated the microbiota of paired RC urine and vaginal samples collected from peri/post-menopausal women. Though limited in sample size, our results suggest that paired mid-vaginal/RC urine samples in peri/post-menopausal women share similar community structure with kappa agreement values indicating substantial agreement, although CST concordance was just a bit lower than reproductive-age women.…”

Section: Discussionmentioning

confidence: 99%

Assessing the Concordance Between Urogenital and Vaginal Microbiota: Can Urine Specimens Be Used as a Proxy for Vaginal Samples?

Brown

Robinson

Shardell

et al. 2021

Front. Cell. Infect. Microbiol.

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BackgroundThe vaginal microbiota play a key role in defense against reproductive tract infections; however, many population-based women’s health studies do not collect vaginal samples. Molecular examinations of urine samples have revealed common vaginal bacteria. We sought to assess the extent that community state type assignments of archived random-catch and clean-catch urine samples agreed with the paired vaginal samples in both reproductive-age and peri/post-menopausal women.ResultsUsing archived samples, we evaluated the microbiota concordance among women in three studies: two with paired mid-vaginal/random-catch urine (N=91 reproductive-age participants and N=13 peri/post-menopausal participants), and one with paired mid-vaginal/clean-catch urine (N=99 reproductive-age participants). Microbiota composition was characterized by sequencing amplicons of the 16S rRNA gene V3-V4 regions and assigned to community state types. Similarity of paired samples was gauged using agreement of community state types and Yue-Clayton θ indices. Analysis of Composition of Microbiomes II indicated which taxa were differently relatively abundant in paired vaginal and urine samples. In reproductive-age women, random-catch and clean-catch urines were 89.0% and 86.9% concordant on five community state types with paired mid-vaginal swabs, and Kappa statistics indicated almost perfect agreement (κrandom-catch=.85, κclean-catch=.81, p<0.0001). A small number of pairs of samples were discordant (23/190, 12%), and discordant pairs tended to be between samples classified to L. iners-dominated and/or low-Lactobacillus states. Concordance and agreement remained similar when dichotomizing the microbiota to Lactobacillus-dominated versus low-Lactobacillus microbiota, as well as when evaluating separately the three subtypes of the low-Lactobacillus community state type IV. Median similarity of paired urine/vaginal samples was high (θrandom-catch=.85, θclean-catch=.88), and a comparison of the random-catch and clean-catch similarity scores showed no significant difference (p=.80). Concordance and similarity were lower for peri/post-menopausal women, but agreement remained substantial (76.9% concordant, κrandom-catch= 0.64, θrandom-catch=.62). Taxonomic-level analysis confirmed these findings.ConclusionsRandom-catch and clean-catch urine samples showed substantial agreement on bacterial composition to paired mid-vaginal samples, indicating that the genitourinary microbiota may be a reliable proxy for assessing the overall composition of the vaginal microbiota via community state types. This data suggests that urine samples can, with proper interpretation, be utilized as a surrogate for developing preliminary data and hypothesis-generating studies.

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“…In the vaginal microbiota, a study reported that the bacterial composition was dependent on menopausal status, in which Lactobacillus was more dominant in pre- and perimenopausal women compared to postmenopausal women 24 . Additionally, local vaginal estrogen treatment in postmenopausal women have shown increased level of Lactobacillus in the vagina 25 and the bladder 26 . Both local vaginal estrogen treatment and treatment with Lactobacillus supplements in patients suffering from rUTIs reduces the risk of infections 25 , 27 , 28 .…”

Section: Introductionmentioning

confidence: 99%

Pre- and postmenopausal women have different core urinary microbiota

Ammitzbøll

Bau

Bundgaard‐Nielsen

et al. 2021

Sci Rep

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Recent studies suggest that alterations in the female urinary microbiota is associated to development of bladder disease. However, the normal microbiota composition and variation in healthy women are poorly described. Moreover, the effects of hormonal changes on microbiota during menopause is not well understood. The aim of our study was to investigate the urinary microbiota in healthy pre- and postmenopausal women without urinary tract symptoms. Microbiota composition in catheterized urine samples was mapped using 16S rRNA gene sequencing. In total, 41 premenopausal and 42 postmenopausal women were initially included. Samples with first PCR amplification concentration below level of the negative control were excluded, resulting in 34 premenopausal and 20 postmenopausal women included in data analysis. Urine from postmenopausal women showed significantly higher alpha diversity compared to premenopausal women. Lactobacillus was the most abundant bacteria in both groups, however the relative abundance of Lactobacillus accounted for 77.8% in premenopausal versus 42.0% in postmenopausal women. In conclusion, urine from premenopausal mostly presented with Lactobacillus dominated urotypes, whereas urine from postmenopausal women presented a more diverse urinary microbiota with higher abundance of the genera Gardnerella and Prevotella. The clinical and pathophysiological implications of this difference remain to be elucidated.

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Vaginal estrogen therapy is associated with increased Lactobacillus in the urine of postmenopausal women with overactive bladder symptoms

Cited by 52 publications

References 39 publications

Recurrent urinary tract infection: Association of clinical profiles with urobiome composition in women

Recurrent urinary tract infection: Association of clinical profiles with urobiome composition in women

Assessing the Concordance Between Urogenital and Vaginal Microbiota: Can Urine Specimens Be Used as a Proxy for Vaginal Samples?

Pre- and postmenopausal women have different core urinary microbiota

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