International Urogynecology Journal (2024) 35:1347–1362

https://doi.org/10.1007/s00192-024-05821-4

REVIEW ARTICLE

The Study of Microbiome of the Female Genital Area in Relation

to Pelvic Floor Dysfunction: A Systematic Review
George Balaouras1 · Polychronis Kostoulas2 · Themistoklis Mikos1 · Dimitrios Balaouras3 · Dimitrios Chitzios3

Received: 9 January 2024 / Accepted: 24 April 2024 / Published online: 11 June 2024
© The International Urogynecological Association 2024

Abstract
Introduction and Hypothesis The aim of this article is to present a systematic literature review focused on microbiome
diversity in women experiencing pelvic floor dysfunction.
Methods Utilizing PubMed/MedLine and Scopus, 25 pertinent studies were meticulously selected for this review.
Results A key theme identified is the potential of microbiomes as diagnostic tools. The findings consistently highlight
Lactobacillus as recurrent microbiota. Additionally, Gardnerella, Streptococcus, Prevotella, Aerococcus, Staphylococcus,
Proteus, and Bifidobacterium species were frequently observed. This suggests the influential role of these microorganisms
in shaping female urological and reproductive health. A deeper understanding of these predominant bacterial genera could
offer invaluable insights into healthy physiological states and various disorders. The complex relationship between microbial
compositions and diverse health conditions paves the way for novel diagnostic and therapeutic approaches. As we further
explore the complexities of microbiomes, their role becomes increasingly crucial in transforming women's health care.
Conclusions These findings emphasize the need for personalized care, integrating the microbiome into a comprehensive
health assessment and treatment framework. This review lays the groundwork for future medical strategies where the micro-
biome is a pivotal element in both preventive and therapeutic care.

Keywords Microbiome · Urinary incontinence · Health outcomes · Lactobacillus

Introduction cannot be overstated, as it plays a pivotal role in multiple

aspects of human health and overall well-being. The impor-
The term “microbiome” encompasses the heterogeneous tance of the microbiome is underscored by numerous key
assemblage of microorganisms, including bacteria, viruses, factors.
fungi, and other microbial entities, that reside in various ana- The term “microbiome” refers to the collection of
tomical regions of the human body. These regions include microorganisms, such as bacteria, fungi, viruses, and other
the gastrointestinal tract, integumentary system, oral cavity, microbial entities, inhabiting and colonizing the human
and reproductive organs. The significance of the microbiome body. Distinct microbial communities are present in vari-
ous anatomical regions of the body, commonly known as
Handling Editor: Annette Kuhn
microbiomes. These include the gut microbiome, vaginal
Editor in Chief: Kaven Baessler
microbiome, and urobiome (also recognized as the urine
microbiome). Microbiomes are of paramount importance in
* Polychronis Kostoulas the preservation of health and the prevention of diseases.
pkost@uth.gr Extensive research has been conducted on the gut microbi-
1
1st Department of Obstetrics & Gynecology, Aristotle
ome, revealing its substantial influence on the overall well-
University of Thessaloniki, Papageorgiou General Hospital, being of the host organism. This phenomenon has a level of
Thessaloniki, Greece effect that may be likened to that of a novel organ inside the
2
Faculty of Public & One Health, University of Thessaly, human body, hence presenting opportunities for therapeu-
Volos, Greece tic intervention. The analysis of gut microbiota composi-
3
Midwifery Department, International Hellenic University, tion and functions has been conducted using novel “omic”
Thessaloniki, Sindos, Greece technologies, which have unveiled its significant role in the

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1348 International Urogynecology Journal (2024) 35:1347–1362

promotion of health and the prevention of illness. The pres- treatments. Additional investigation is required in order to
ence of dysbiosis in the gut microbiome has been linked to comprehensively clarify the structure, roles, and therapeutic
a range of disorders, such as inflammatory bowel diseases, possibilities of these microbiomes.
obesity, liver diseases, autoimmune diseases, and Crohn's It is crucial to recognize that the composition of the
disease [1]. Likewise, the vaginal microbiota assumes a piv- microbiome is influenced by a variety of factors, including
otal role in the prevention of infections and the preservation genetics, dietary habits, environmental conditions, phar-
of vaginal well-being. The disturbance of the vaginal micro- maceutical interventions, and personal lifestyle choices.
biome has been associated with a higher prevalence of bacte- Therefore, maintaining a balanced and diverse microbiome
rial vaginosis and candidal vulvovaginitis. There is a positive is key to promoting overall well-being. Incorporating pro-
correlation between more variety in the vaginal microbiome biotics, prebiotics, and a diet rich in fiber and fermented
and a higher prevalence of inflammatory diseases [2]. In foods has demonstrated a beneficial effect on sustaining a
recent years, there has been a growing interest in the urobi- healthy microbiome [12]. Additionally, ongoing research in
ome, also known as the urine microbiome, owing to its prob- this field is progressively enhancing our understanding of the
able involvement in urological illnesses. The presence of importance of the microbiome, potentially leading to signifi-
dysbiosis in the urobiome has been suggested to be a contrib- cant developments in personalized medicine and health care.
uting factor to many diseases, including overactive bladder
(OAB), urge urinary incontinence, and bladder cancer [3].
The variation of the vaginal microbiota across various races Materials and Methods
has been observed, underscoring its significance in the realm
of gynecological health [4]. The urobiome plays a crucial Search Strategy
role in the preservation of urothelial integrity, the preven-
tion of urinary tract infections (UTIs), and the enhancement A systematic online search for published literature was
of local immunological activity. Advancements in bacterial carried out in PubMed/MedLine and Scopus databases,
cultivation and DNA sequencing methods have unveiled including unpublished articles, with the MESH (medical
a previously undiscovered variety within the urinary tract subject heading) terms “urobiome, vaginal microbiome,
microbiome (urobiome) [5, 6]. The possible influence of this gut microbiome” and “urine microbiota, vaginal microbiota,
microbial ecosystem on health, especially regarding UTIs, gut microbiota” in combination with “pelvic floor dysfunc-
holds considerable clinical significance [7]. The presence of tion, stress urinary incontinence, urge urinary incontinence,
dysbiosis in the urobiome has been associated with a height- overactive bladder, pelvic organ prolapse, feral incontinence,
ened susceptibility to UTIs, nephrolithiasis, and lower uri- chronic pelvic pain and sexual dysfunction.” The search time
nary tract dysfunction. The urobiome has promise as a viable period was up to 1 October 2022 and we limited the search
target for therapeutic approaches in the realm of urological language to English, with no restrictions on country or pub-
disorders [8]. The significance of the microbiome in the pre- lication state. A flowchart of the systematic search process
vention and progression of illnesses goes beyond the urinary is shown in Fig. 1.
tract [9, 10]. The association between the gut microbiota
and many pathological disorders has been established, and Study Selection
there is ongoing discussion over its makeup and functions.
The potential involvement of the microbiome in the patho- We included the studies that fulfilled the following inclusion
physiology of vesicoureteral reflux (VUR), a disease associ- criteria: case–control and cohort studies; provision of origi-
ated with kidney impairment, has been suggested [11]. The nal data. Excluded studies were reviews; studies for which
role of the microbiome in the pathogenesis of endometrial the full text was not available; and studies with insufficient
cancer has also been suggested, as observed variations in the data.
vaginal microbiota have been identified between individuals No ethical approval was required for this review.
with and those without endometrial cancer. Furthermore,
the microbiome has been investigated in relation to urinary
calculi, whereby Lactobacillus spp. have been shown to con- Results
tribute to the maintenance of urinary tract homeostasis. In
summary, the microbiomes, including the urobiome, vaginal Table 1 gives a summary of the results of the studies. The
microbiome, and gut microbiome, are vital in the preserva- distribution of identified bacterial species across the studies
tion of well-being and the mitigation of illnesses. The pres- is graphically represented in Fig. 2.
ence of dysbiosis in these microbiomes has been linked to The study by Komesu et al. [13] was designed to com-
a range of illnesses and diseases, underscoring the need to pare vaginal and urinary microbiomes in women with mixed
comprehend and investigate the microbiome for therapeutic urinary incontinence (MUI) with asymptomatic controls. It
International Urogynecology Journal (2024) 35:1347–1362 1349

Fig. 1  Preferred Reporting

Items for Systematic reviews
and Meta-Analyses flow
diagram

was nested in an ongoing trial, comparing a behavioral/pel- in subjects with urinary urgency/urgent urinary incontinence
vic floor exercise intervention plus midurethral sling versus progression, with a higher relative abundance of the genus
midurethral sling alone for MUI. DNA was collected from Streptococcus (16S ribosomal RNA gene). This study con-
participants for analysis and conventional urine culture. The cludes that gut microbiome alterations may be associated
bacterial communities were to be identified through poly- with OAB symptom progression, and proton pump inhibitor
merase chain reaction (PCR) amplification and sequencing (PPI) usage could exacerbate this risk.
of the bacterial 16S ribosomal RNA gene from collected The study by Thomas-White et al. [15] was aimed at
samples. The urgency urinary incontinence (UUI) microbi- examining the link between postoperative UTIs and pre-
ome was composed of increased Gardnerella and decreased operative urinary bacteria in urogynecological surgery
Lactobacillus, with cohorts differing in the predominance of patients. Preoperative vaginal, perineal, and urine sam-
Lactobacillus species. ples were analyzed, with the urine microbiome especially
The study by Okuyama et al. [14] was aimed at assess- associated with postoperative UTI risk. The findings
ing the influence of the gut microbiome on OAB symptom revealed that UTI risk correlated with a decrease in Lac-
progression. After analyzing gut microbiomes from fecal tobacillus iners and an increase in various uropathogens.
samples, the results showed a distinct microbiota structure These insights underscore the potential microbial factors
Table 1  Results
1350

References Publication journal Year of Τype of study Microbiome type Study aim Sample size Method of analysis Microbiota found/
publica- main findings
tion

Komesu et al. [13] International Urogy- 2017 Case–control study Vaginal and urinary To compare the Total: 210 16S rRNA sequenc- Lactobacillus and
necology Journal microbiome vaginal and uri- Cases: 126 MUI ing Gardnerella spp.
nary microbiomes
Controls: 84
in women with
mixed urinary
incontinence and
asymptomatic
controls
Okuyama et al. [14] International Urol- 2022 Case–control study Gut microbiome To assess the Total: 667 16S rRNA sequenc- Streptococcus, Lacto-
ogy and Nephrol- influence of gut Cases: 126 with ing bacillus, Roseburia
ogy microbiome on urinary urgency and Proteus spp.
overactive bladder and urge urinary
symptoms progres- incontinence
sion
Controls: 541
Thomas-White et al. International Urogy- 2018 Cohort study Urinary, vaginal, To assess the asso- Total: 104 16S rRNA sequenc- Lactobacillus, Gard-
[15] necology Journal and perineal ciation of post- ing nerella, Anaerococ-
microbiome operative urinary cus, and Corynebac-
tract infection with terium spp.
bacteria in preop-
erative samples of
catheterized urine
Veit-Rubin et al. [16] Neurourology and 2019 Case–control study Vaginal microbiome To identify differ- Total: 40 16S rRNA sequenc- Veillonella spp.
Urodynamics ences in the vagi- Cases: 19 (14 after ing
nal microbiomes mesh exposure, 5
of women after after contraction)
transvaginal mesh
Controls: 21
surgery for pelvic
organ prolapse
with and without
mesh-associated
complications
Chen et al. [17] Nursing Research 2021 Cohort study Vaginal microbiome To examine asso- Total: 20 16S rRNA sequenc- Lactobacillus spp.
during menstrua- ciations between ing
tion dysmenorrhea
symptom-based
phenotypes and
vaginal microbi-
ome compositions
on- and off-menses
International Urogynecology Journal (2024) 35:1347–1362
Table 1  (continued)
References Publication journal Year of Τype of study Microbiome type Study aim Sample size Method of analysis Microbiota found/
publica- main findings
tion

Wei et al. [18] Annals of Clinical 2020 Case–control study Microbiota along the To explain the Total: 50 16S rRNA sequenc- Lactobacillus spp.
Microbiology and female reproduc- pathogenesis of ing
Antimicrobials tive tract endometriosis Cases: 36 patients
with endometriosis
Controls: 14
Thomas-White et al. American Journal 2017 Cross-sectional Urinary microbiome To study the cross- Total: 197 16S rRNA sequenc- Lactobacillus and
[19] of Obstetrics and study sectional relation- ing Gardnerella spp.
Gynecology ships between
female urinary
microbiota features
and demographic
and clinical
characteristics of
International Urogynecology Journal (2024) 35:1347–1362

women undergo-
ing stress urinary
incontinence
surgery
Nickel et al. [20] Journal of Urology 2016 Cohort study Lower urinary tract To compare culture- Total: 233 Ibis T-5000 Uni- Candida and Saccha-
microbiota independent versal Biosensor romyces spp.
assessment of system technology
microbiota of the
lower urinary
tract in standard
culture negative
female patients
with urological
chronic pelvic pain
syndrome who
reported symptom
flare vs those who
did not report a
flare
Braundmeier-Flem- Scientific Reports 2016 Case–control study Stool microbiome To find underlying Total: 34 16S rDNA sequenc- E. sinensis, C. aerofa-
ing et al. [21] mechanisms and Cases: 18 patients ing ciens, F. prausnitzii,
diagnostic bio- with interstitial O. splanchnicus,
markers of intersti- cystitis and L. longoviformis
tial cystitis/bladder
Controls: 16
pain syndrome
1351
Table 1  (continued)
1352

References Publication journal Year of Τype of study Microbiome type Study aim Sample size Method of analysis Microbiota found/
publica- main findings
tion

Okamoto et al. [22] World Journal of 2021 Cross-sectional Gut microbiome To explore associa- Total: 1,113 16S rRNA sequenc- Bifidobacterium and
Urology study tions between the ing Faecalibacterium
gut microbiome spp.
and overactive
bladder with daily
urinary urgency
among individu-
als reporting this
diagnosis within a
single community
Li et al. [23] BMC Urology 2022 Cross-sectional Urinary microbiome To examine the cor- Total: 70 16S rRNA sequenc- Lactobacillus, Strep-
study relation between Cases: 53 patients ing tococcus, Gard-
urinary microbi- with moderate/ nerella, Prevotella,
ome and the sever- severe overactive Methylobacterium,
ity of overactive bladder Acinetobacter, and
bladder Sphingomonas spp.
Controls: 17 mild
patients
Wu et al. [24] Frontiers in Cel- 2017 Cross-sectional Urinary microbiome To characterize the Total: 55 16S rRNA sequenc- Proteus, Aerococ-
lular and Infection study female urinary Cases: 30 women ing cus, Prevotella, and
Microbiology microbiome with overactive Lactobacillus spp.
associated with bladder
overactive bladder
Controls: 25
and investigate
the relationships
between the uri-
nary microbiome
and psychological
factors
Curtiss et al. [25] European Journal 2017 Case–control study Urinary microbiome To characterize the Total: 98 16S rRNA sequenc- Proteus, Lactobacil-
of Obstetrics, microbiome in Cases: 63 women ing lus, Staphylococcus
Gynecology, and healthy women with overactive and Streptococcus
Reproductive with no bladder bladder spp.
Biology symptoms and to
Controls: 35
compare this with
the bladder micro-
biome in patients
with overactive
bladder syndrome
International Urogynecology Journal (2024) 35:1347–1362
Table 1  (continued)
References Publication journal Year of Τype of study Microbiome type Study aim Sample size Method of analysis Microbiota found/
publica- main findings
tion

Karstens et al. [26] Frontiers in Cel- 2016 Case–control study Urinary microbiome To determine how Total: 20 16S rRNA sequenc- Lactobacillus,
lular and Infection the urinary micro- ing Proteus, Prevotella,
Microbiology biome is different Cases: 10 women Bifidobacterium,
between women with urge urinary Gardnerella,
with and without incontinence Escherichia, and
urge urinary Controls: 10 Shigella spp.
incontinence
Chen et al. [27] International Urogy- 2018 Cohort study Urinary microbiome To explore the Total: 39 16S rRNA sequenc- Escherichia, Lacto-
necology Journal microbiota of ing bacillus, Klebsiella,
refractory urge and Staphylococcus
incontinence spp.
patients and
coexistent recur-
International Urogynecology Journal (2024) 35:1347–1362

rent urinary tract

infection
Pearce et al. [28] American Journal 2015 Cohort study Urinary microbiome To characterize the Total: 182 16S rRNA sequenc- Lactobacillus, Gard-
of Obstetrics and urinary microbiota ing nerella, Prevotella,
Gynecology in women who are Enterobacteriaceae,
planning treatment Staphylococcus,
for urge urinary Aerococcus, and
incontinence and Bifidobacterium
to describe clinical spp.
associations with
urinary symptoms,
urinary tract infec-
tion, and treatment
outcomes
Nickel et al. [29] Journal of Clinical 2019 Case–control study Urine microbiome To survey the uri- Total: 363 Polymerase chain Lactobacillus gasseri,
Medicine nary microbiota of Cases: 181 female reaction electro- Corynebacterium
females diagnosed interstitial cystitis/ spray ionization spp.
with interstitial bladder pain syn- time-of-flight
cystitis/bladder drome mass spectrometry
pain syndrome
Controls: 182
1353
Table 1  (continued)
1354

References Publication journal Year of Τype of study Microbiome type Study aim Sample size Method of analysis Microbiota found/
publica- main findings
tion

Abernethy et al. [30] Obstetrics and 2017 Cross-sectional Urinary microbiome To investigate dif- Total: 40 16S rRNA sequenc- Lactobacillus spp.
Gynecology study ferences in the uri- ing
nary microbiome Cases: 20 women
and cytokine levels with interstitial
between women cystitis
with and those Controls: 20
without interstitial
cystitis and to
correlate differ-
ences with scores
on standardized
symptom severity
scales and depres-
sion and anxiety
screening tools
Arya et al. [31] Neurourology and 2018 Case–control study Stool microbiome To report the ration- Total: 123 16S rRNA sequenc- Analyses are ongoing
Urodynamics ale, design, and the Cases: 82 women ing
specific methodol- with fecal inconti-
ogy of an ongoing nence
nested observa-
Controls: 41
tional study that
will determine the
association of the
metabolite and
microbial compo-
sition of stool with
fecal incontinence
Wessels et al. [32] Scientific Reports 2021 Cross-sectional Uterine bacteria To prove that the Total: 21 16S rRNA sequenc- Actinobacteria
study (endometrial endometrial Cases: 12 with ing phylum, Oxalo-
microbiota) microbiota is more endometriosis bacteraceae,
diverse in people Streptococcaceae,
Controls: 9
with endometriosis and Burkholde-
than in sympto- riaceae families and
matic controls Tepidimonas and
Ralstonia genera
International Urogynecology Journal (2024) 35:1347–1362
Table 1  (continued)
References Publication journal Year of Τype of study Microbiome type Study aim Sample size Method of analysis Microbiota found/
publica- main findings
tion

Price et al. [33] American Journal 2020 Case–control study Urinary microbiome To test that the Total: 309 Expanded quantita- Lactobacillus spp.,
of Obstetrics and bladder urobiome tive urine culture Streptococcus angi-
Gynecology differs between Cases: 159 with uri-protocol and nosus, Staphylococ-
women in the nary incontinence matrix-assisted cus epidermidis,
control group and (stress and urge) laser desorption/ Aerococcus urinae,
in women affected Controls: 150 ionization time- and Gardnerella
by urinary incon- of-flight mass vaginalis
tinence spectrometry
Chao et al. [34] Annals of Transla- 2021 Case–control study Vaginal microbiome To investigate the Total: 128 16S rRNA sequenc- Clostridium spp.,
tional Medicine specific vaginal Cases: 62 (37 ing Alloscardovia omni-
microbiome in the women with endo- colens, Veillonella
differential diagno- metriosis-/adeno- montpellierensis,
sis of endometrio- and Lactobacillus
International Urogynecology Journal (2024) 35:1347–1362

myosis-associated
sis/adenomyosis- chronic pelvic spp.
associated chronic pain, 25 women
pelvic pain from with chronic pel-
other types of vic pain without
chronic pelvic pain endometriosis/
adenomyosis)
Controls: 66
Li et al. [35] Journal of Medical 2021 Case–control study Gut microbiome To explore the Total: 46 16S rRNA gene Unidentified Rumi-
Internet Research difference in the Cases: 24 women sequencing and nococcaceae, Bifi-
composition of with hypoactive liquid chroma- dobacterium, and
gut microbes and sexual desire tography mass Lactobacillus spp.
fecal metabolites disorder spectrometry
between women
Controls: 22
with hypoactive
sexual desire dis-
order and healthy
controls
Pearce et al. [36] mBio 2014 Case–control study Urinary microbiome The comparison of Total: 118 16S rRNA gene Actinobaculum, Actin-
urinary microbi- Cases: 60 urge uri- sequencing and omyces, Aerococ-
ome in women nary incontinence expanded quantita- cus, Arthrobacter,
with and without tive urine culture Corynebacterium,
Controls: 58
urge urinary Gardnerella, Oli-
incontinence gella, Staphylococ-
cus, Streptococcus,
and Lactobacillus
spp.
1355
 1356 International Urogynecology Journal (2024) 35:1347–1362

contributing to postoperative UTI risk, guiding toward bet-

teroides, Aerococ-
ter preoperative evaluations and interventions.

16S rRNA sequenc- Lactobacillus, Bac-

cus, Actinomyces,
Gardnerella and
Microbiota found/

Prevotella spp.
The study by Veit-Rubin et al. [16] was aimed at dis-
main findings

cerning the differences in vaginal microbiomes in women

post-transvaginal mesh surgery for pelvic organ prolapse,
with and without mesh-associated complications. Meth-
ods entailed DNA isolation and 16S rRNA gene sequenc-
ing to quantify microbial diversity. The findings showed
Method of analysis

a higher abundance of Veillonella spp. in patients with

mesh contraction, although no significant vaginal microbi-
omic dysbiosis was observed in those with mesh exposure.
This study hints at the association of Veillonella spp. with
ing

mesh contraction, necessitating larger cohorts for further

insights.
with urge urinary
Cases: 20 women

The study by Chen et al. [17] investigated the associations

incontinence

between dysmenorrhea symptom-based phenotypes and vag-

Controls: 30
Sample size

inal microbiome compositions during menstruation. A pilot

Total: 50

study with 20 women, categorized into three dysmenorrhea

phenotypes, was conducted. Vaginal swabs were collected
during and outside menstruation, and analyzed using 16S
dynamics of inter-

in the bladder and

nary incontinence
rences of bacteria
actions/co-occur-

with and in those

vagina in women

without urge uri-

To understand the

rRNA gene sequencing. Significant microbiome composi-

tion differences were observed among the phenotypes during
menstruation, particularly a lower lactobacilli level and a
Study aim

higher abundance of certain bacteria in the severe symptom

phenotype (Prevotella, Atopobium, and Gardnerella). This
study suggests potential new intervention targets or biomark-
Vaginal and bladder

ers for dysmenorrhea, warranting larger studies.

Microbiome type

The study by Wei et al. [18] explored the microbiota com-

microbiome

position along the female reproductive tract in 36 endome-

triosis patients and 14 controls. Utilizing 16S rRNA ampli-
con sequencing on samples from various reproductive tract
regions, they discovered a significant difference in microbial
community diversity starting from the cervical mucus in
Case–control study

endometriosis patients, indicating that cervical microbiota

Τype of study

could be a risk indicator for endometriosis. The study high-

lighted a decrease in Lactobacillus and an increase in certain
microbes in endometriosis patients, suggesting a potential
role of microbiota in endometriosis pathogenesis.
The study by Thomas-White et al. [19] was aimed at
publica-
Year of

exploring the urinary microbiota's relationship with demo-

2022
tion

graphic and clinical characteristics in women undergoing

stress urinary incontinence (SUI) surgery. Preoperative
lular and Infection
Publication journal

urine specimens from 197 women were analyzed using

Frontiers in Cel-

Microbiology

16S rRNA gene sequencing to qualitatively assess bacte-

rial composition. The study design involved comparing
phylogenetic relatedness and microbial alpha diversity
with demographics and symptoms, providing insights
into the urinary microbiota of women with SUI. The study
Table 1  (continued)

showed that women having surgery for SUI had noticeable

Nardos et al. [37]

urinary microbes (Lactobacillus, Gardnerella). Through

References

a cross-sectional examination, it was found that a higher

variety of these microbes correlated with urgent urinary
incontinence symptoms, hormonal levels, and body mass
International Urogynecology Journal (2024) 35:1347–1362 1357

Fig. 2  The distribution of iden-

tified bacterial species

index. However, there was no observed link between these The study by Okamoto et al. [22] examined the link
microbes and symptoms of SUI. between the gut microbiome and OAB with daily urinary
The study by Nickel et al. [20] was aimed at comparing urgency in 1,113 individuals from a single community.
the microbiota of the lower urinary tract in female patients Using next-generation sequencing of 16S rRNA genes from
with urological chronic pelvic pain syndrome (UCPPS), fecal samples, they found significant differences in gut
particularly between those who reported a symptom flare microbial content between individuals with OAB and daily
and those who did not. Utilizing the Ibis T-5000 Universal urgency and those without OAB. Individuals reporting OAB
Biosensor system technology, they analyzed initial stream with daily urinary urgency demonstrated a lower bacterial
(VB1) and midstream (VB2) urine specimens from 233 diversity, whereas the results cluster differently in the non-
UCPPS patients. The findings revealed no significant dif- OAB groups. The relative abundance of the genus Bifido-
ferences in species composition between flare and nonflare bacterium was significantly lower among those reporting
cases. However, a significantly higher prevalence of fungi daily urgency. By contrast, the relative abundance of genus
(Candida and Saccharomyces) was observed in the flare Faecalibacterium was significantly higher in this group.
group, especially in VB2 specimens, even after adjust- The study by Li et al. [23] explored the correlation
ing for antibiotic use and menstrual phase. This suggests between urinary microbiome and OAB severity in 70 OAB
that the presence of certain fungi could be associated with patients. Using 16S rRNA gene sequencing, they found
symptom flare in women with UCPPS. lower bacterial diversity and richness in patients with mild
The study by Braundmeier-Fleming et al. [21] investi- OAB than in moderate/severe cases. There was a positive
gated stool-based biomarkers in patients with interstitial correlation between OAB symptom severity and both rich-
cystitis (IC)/bladder pain syndrome (BPS). They analyzed ness and diversity indices. Moreover, certain bacterial gen-
stool samples from female patients with IC and healthy era including Lactobacillus and Streptococcus (Firmicutes
controls, identifying that specific bacterial species were phylum), Gardnerella (Actinobacteria phylum), Prevotella
significantly reduced in patients with IC. Quantitative PCR (Bacteroidetes phylum), Methylobacterium, Acinetobacter,
of stool DNA demonstrated significantly reduced levels of and Sphingomonas (Proteobacteria phylum) correlated sig-
E. sinensis, C. aerofaciens, F. prausnitzii, O. splanchnicus, nificantly with OAB sub-symptom severity, suggesting a
and L. longoviformis in microbiota of patients with IC. potential interplay between bladder microbiota and OAB
These species, deficient in IC pelvic pain (DIPP), were symptom severity.
further evaluated using receiver-operator characteris- The study by Wu et al. [24] explored the urinary micro-
tic analyses, and DIPP species emerged as potential IC biome and psychological factors in 30 women with OAB
biomarkers. The identified species and metabolites could and 25 controls. They found that by using 16S rRNA gene
serve as potential IC biomarkers, suggesting that the func- sequencing, bacterial diversity and richness (Proteus, Aero-
tional changes in the IC microbiome might be therapeutic coccus, Lactobacillus, and Prevotella) in patients with OAB
targets for chronic pelvic pain. patients and identified correlations between psychological
1358 International Urogynecology Journal (2024) 35:1347–1362

conditions and urinary microbiome characteristics in women Lactobacillus (45%) or Gardnerella (17%). The results indi-
with OAB, suggesting an intertwined relationship between cated that many women with UUI, with no signs of infection,
psychological factors, urinary microbiome, and OAB patho- had urinary bacterial DNA. The sequence status was asso-
genesis, which warrants further investigation. ciated with baseline UUI episodes, treatment response and
The study by Curtiss et al. [25] compared the bladder post-treatment UTI risk, shedding light on the potential role
microbiome in 63 women with OAB with that of 35 healthy of the urinary microbiome in UUI and its treatment [28].
controls, using bacterial colonies lysed and polymerase The study conducted by Nickel et al. [29] was aimed at
chain reaction undertaken to amplify the 16S ribosomal analyzing the urine microbiota of women diagnosed with
RNA gene. The results revealed no significant difference in IC/BPS alongside matched control participants, under the
the mean number of bacterial genera between the groups, National Institutes of Health Multidisciplinary Approach to
although uropathogenic bacteria Proteus were more com- the Study of Chronic Pelvic Pain (MAPP) research network,
mon, and the genus Lactobacillus was less common in using a culture-independent methodology. The investigation
patients with OAB. Overall the most commonly grown bac- employed the Plex-ID molecular diagnostic platform, which
teria were Staphylococcus (grown in 59% of samples), Strep- utilizes polymerase chain reaction electrospray ionization
tococcus (51%), Corynebacterium (37%), and Lactobacillus time-of-flight mass spectrometry for a comprehensive iden-
(28%). This suggests a variation in microbial composition tification of bacterial and select fungal species in midstream
associated with OAB, providing insights into its potential urine specimens. The findings revealed that urine samples
role in the condition. from 181 female participants with IC/BPS and 182 female
The study by Karstens et al. [26] was aimed at explor- control participants detected a total of 92 species (41 gen-
ing the urinary microbiome's differences between women era), without significant differences in the overall species
with and those without UUI and its association with UUI composition between the two groups. A trend toward over-
severity. Through urine collection from 10 women with UUI abundance of Lactobacillus gasseri was noted in participants
and 10 with normal bladder function, bacterial 16S rRNA with IC/BPS), but with a lower prevalence of Corynebac-
gene sequencing revealed a polymicrobial community in terium than in control participants. The relative abundance
both groups. They identified bacteria (Lactobacillus, Pro- data analysis mirrored the prevalence data differences, with
teus, Prevotella, Bifidobacterium, Gardnerella, Escherichia, no significant differences in most species or genus abun-
Shigella) with significantly different relative abundances dance, other than Lactobacillus gasseri and Corynebacte-
between groups. An increase in UUI symptom severity cor- rium. No cause-and-effect conclusion was drawn from these
related with decreased microbial diversity, suggesting the observations.
potential role of the urinary microbiome in UUI pathophysi- The study by Abernethy et al. [30] was aimed at investi-
ology and its association with clinical severity. gating the urinary microbiome and cytokine levels in women
The study by Chen et al. [27] investigated the urinary with and without IC, and correlating these with symptom
microbiome in patients with refractory urge incontinence severity and mental health indicators. The methodology
and recurrent UTIs. By collecting midstream urine sam- involved collecting catheterized urine samples from partici-
ples during acute symptomatic episodes from 39 patients pants for bacterial ribosomal RNA sequencing and stand-
over 2 years (16S rRNA), the authors identified a diverse ard immunoassays to analyze the urinary microbiome and
urinary microbiota (Escherichia, Lactobacillus, Klebsiella, cytokine levels respectively. The results revealed that the
Staphylococcus). They discovered instances of recurrent urinary microbiome of participants with IC was less diverse
UTIs caused by both persistent and newly infecting E. coli and was less likely to contain Lactobacillus acidophilus.
strains, shedding light on the microbial aspect of refractory Additionally, higher levels of proinflammatory cytokines
urge incontinence and recurrent UTIs in these patients. such as macrophage-derived chemokines and interleu-
The study by Pearce et al. [28] was aimed at character- kin-4 were observed in participants with IC. It is unknown
izing the urinary microbiota in women planning treatment whether this represents causality and whether the effect of
for UUI and understand its clinical associations with urinary alterations to the urinary microbiome is mediated through
symptoms, UTI risk, and treatment outcomes. Catheterized an inflammatory response.
urine samples were collected from participants in a multisite The study led by Arya et al. [31] was aimed at investigat-
randomized trial who showed no clinical evidence of UTI. ing the association between the metabolite and microbial
Utilizing 16S ribosomal RNA gene sequencing, partici- composition of stool with fecal incontinence (FI) in women.
pants were dichotomized as either DNA sequence-positive The methodology entailed enrolling women with FI from
or DNA sequence-negative. Οver half (51.1%) of the par- the Controlling anal incontinence in women by performing
ticipants were found to be DNA sequence-positive. In DNA anal exercises with biofeedback or loperamide (CAPABLe)
sequence-positive samples, eight major bacterial clusters trial and selecting age-matched women without FI as con-
were identified, often dominated by a single genus, mainly trols. Participants were instructed to collect stool samples,
International Urogynecology Journal (2024) 35:1347–1362 1359

analyzed for stool metabolites, through targeted metabolic be associated with UI, with a greater culturable species rich-
profiling and for stool microbiota, through 16S rRNA gene ness observed in the UI cohorts than in the continent control
sequencing. Analyses are still ongoing. cohort, suggesting a potential link between bladder micro-
The study conducted by Wessels et al. [32] was aimed at bial diversity and UI.
exploring the differences in uterine bacteria (endometrial The study by Chao et al. [34] was aimed at analyzing the
microbiota) between individuals with surgically confirmed vaginal microbiome in women to differentiate chronic pel-
presence or absence of endometriosis, by utilizing next-gen- vic pain (CPP) associated with endometriosis/adenomyosis
eration 16S rRNA gene sequencing. The method involved (EM/AM) from other types of CPP, and to understand the
comparing the endometrial microbiota of 12 individuals role of the vaginal microbiome in the mechanism of EM/
with endometriosis and 9 symptomatic controls (those with AM-associated CPP. The study involved 37 women with
pelvic pain but surgically confirmed absence of endometrio- EM/AM-associated CPP, 25 women with chronic pelvic pain
sis and diagnosed with other benign gynecological condi- syndrome (CPPS) without EM/AM, and 66 women without
tions). The findings revealed that the endometrial micro- CPPS, all of whom were free from human papillomavirus
biota of individuals with endometriosis was more diverse (HPV) infection. The vaginal microbiome composition was
than that of the symptomatic controls. Specifically, bacterial determined using 16S rRNA sequencing. The results show-
taxa enriched in the endometrial microbiota of individuals cased that EM/AM-associated CPP had a higher presence
with endometriosis belonged to the Actinobacteria phylum of Clostridium butyricum, C. disporicum, Alloscardovia
(Gram-positive), Oxalobacteraceae (Gram-negative) and omnicolens, and Veillonella montpellierensis, and a lower
Streptococcaceae (Gram-positive) families, and the Tepidi- presence of Lactobacillus jensenii, L. reuteri, and L. iners.
monas (Gram-negative) genus. In contrast, those enriched in Specific relative abundance thresholds of C. disporicum and
the symptomatic controls belonged to the Burkholderiaceae L. reuteri were identified to have a differential diagnostic
(Gram-negative) family, and the Ralstonia (Gram-negative) sensitivity and specificity of 81.08% and 52.0% respectively.
genus. These results imply that the endometrial microbiota Adding serum CA125 to the analysis increased the sensitiv-
are altered in individuals with endometriosis. ity to 89.19% while maintaining the specificity at 52.0%. The
The study by Price et al. [33] was aimed at exploring analysis pointed out seven differentially regulated pathways
the differences in the bladder urobiome between continent among the three groups. In conclusion, the vaginal micro-
women and those affected by UI, and to understand the biome in patients with EM/AM-associated CPP exhibited
potential correlation of urobiome characteristics with UI. significantly higher alpha (phylogenetic) diversity and dif-
Employing a cross-sectional design, urine specimens from ferent microbial counts compared with the other two groups,
309 adult women were collected via transurethral catheteri- indicating that the vaginal microbiome might play a role in
zation and categorized into three cohorts (continent con- EM/AM-associated CPP, and combined analysis of vaginal
trol, SUI, and UUI) based on responses to the Pelvic Floor biomarkers and serum CA125 could offer a new method for
Distress Inventory questionnaire. The cultured urobiome differentiating EM/AM-associated CPP.
was examined using an expanded quantitative urine culture The study by Li et al. [35] was aimed at examining and
protocol, and microbes were identified down to the species evaluating the differences in the composition of gut microbes
level with matrix-assisted laser desorption and ionization and fecal metabolites between women with hypoactive sex-
time-of-flight mass spectrometry. The findings indicated ual desire disorder (HSDD) and healthy controls. Using an
a higher detection frequency of bacteria in the UI cohorts online recruitment method, the study enlisted 24 women
than in the control cohort (86% in SUI, 81% in UUI vs 57% with HSDD and 22 age-matched healthy controls. The analy-
in controls). Notably, the study revealed that the most fre- sis was conducted on fecal samples collected from these
quently detected species varied across cohorts. In the con- participants using 16S ribosomal RNA gene sequencing for
tinent control cohort, Lactobacillus iners and Streptococ- microbiome analysis and untargeted liquid chromatogra-
cus anginosus were the most common, whereas in the SUI phy–mass spectrometry for metabolome analysis. The results
cohort, S. anginosus dominated, and in the UUI cohort, S. showed that women with HSDD had a lower abundance of
anginosus, Lactobacillus gasseri, Aerococcus urinae, and Ruminococcaceae and a higher abundance of Bifidobacte-
Gardnerella vaginalis were frequently detected. However, rium and Lactobacillus. Additionally, fecal samples from
only the Actinotignum schaalii, A. urinae, Aerococcus san- women with HSDD exhibited significantly altered metabolic
guinicola, and Corynebacterium lipophile groups were signatures compared with those from healthy controls. The
found at significantly higher mean abundances in one of the abundance of Bifidobacterium, Lactobacillus, and certain
UI cohorts than in the control cohort. Increased alpha diver- fecal metabolites correlated negatively with the sexual desire
sity was observed in both UI cohorts, with species richness, score, whereas the number of Ruminococcaceae correlated
but not evenness, strongly associated with UI. In summary, positively with the sexual desire score across all subjects.
the culturable bladder urobiome composition was found to In conclusion, the study identified significant differences in
1360 International Urogynecology Journal (2024) 35:1347–1362

gut microbes and metabolic signatures between women with with UUI, along with differences in central bacteria to the
HSDD and healthy controls, suggesting that these prelimi- overall community structure, hinting at a potential microbi-
nary findings could be instrumental in devising strategies to ome-related aspect in the understanding and management
modulate human sexual desire by altering gut microbiota. of UUI.
The study by Pearce et al. [36] was aimed at investigat-
ing the differences in the urinary microbiomes of women
with UUI and those without it, to understand if bacteria Discussion
contribute to UUI. Utilizing 16S rRNA gene sequencing
and extended quantitative urine culture techniques, the The manuscript effectively highlights the significant role
researchers analyzed the urine collected via a transurethral of microbiomes in various aspects of female urological
catheter from women with UUI and a control group. The and reproductive health. It emphasizes the complex rela-
results revealed that the urinary microbiomes in women tionship between the microbial composition in different
with and without UUI differed significantly. Specifically, parts of the female reproductive and urinary systems and a
the UUI microbiome had increased levels of Gardnerella range of conditions, including urinary incontinence, OAB,
and decreased levels of Lactobacillus compared with the endometriosis, fecal incontinence, and HSDD [35]. The
non-UUI microbiome. Additionally, nine genera (including discussion consistently examines how microbial diversity,
Actinobaculum, Corynebacterium, Gardnerella, and oth- or the lack thereof, affects the pathophysiology of urologi-
ers) were cultured more frequently from the UUI cohort. cal and gynecological disorders. For instance, a decrease
Although Lactobacillus was found in both groups, there in microbial diversity is often positively associated with
were species-level distinctions with Lactobacillus gasseri the increased severity of symptoms in conditions such as
being more common in the UUI cohort, and Lactobacillus UUI [26] and OAB [24]. Microbial genera and species, par-
crispatus being more common in the control group. This ticularly Lactobacillus, are identified as key in maintaining
study suggests that there might be notable differences in the microbial balance, with their disruption being linked to the
urinary microbiomes between women with and those with- onset of various diseases.
out UUI, which could have implications in the prevention, Furthermore, the nuanced differences in microbiome
diagnosis, or treatment of UUI. compositions between healthy individuals and those with
The study by Nardos et al. [37] was aimed at examining certain medical conditions offer promising diagnostic poten-
the differences in the vaginal and bladder microbial commu- tial. For instance, the abundance of specific bacteria and
nities between women with UUI and those without it. They the occurrence of particular microbial species may serve as
collected vaginal swabs and catheterized urine specimens biomarkers for conditions such as endometriosis or UUI as
from 20 women with UUI and 30 women without UUI. By mentioned [21]. This finding underscores the possibility of
sequencing the V4 region of the bacterial 16S rRNA gene leveraging microbiome modification as a therapeutic strat-
and utilizing various diversity metrics and network analy- egy. It suggests the use of probiotics or other microbiota-
sis, they analyzed the microbial interactions. The findings altering methods as viable options for alleviating symptoms
showed no significant discrepancies in the vaginal or blad- or treating specific medical conditions [12].
der microbiomes between the cases and controls in terms of Additionally, a notable association exists between the
alpha and beta diversity. However, two distinct microbiome composition of the microbiome and symptom severity in
clusters were identified in both the bladder and vagina, with various medical conditions. Some diseases demonstrate a
one dominated by the Lactobacillus genus and the other link between greater bacterial diversity or specific bacte-
being more diverse. Network-based analysis revealed dif- rial concentrations and a decrease in symptom severity. The
ferences in vaginal and bladder microbial networks between manuscript further clarifies that microbiomes in different
cases and controls. In the vagina, although the numbers of anatomical regions are interconnected, not isolated. For
genera and subgroup clusters were similar in the two groups, instance, alterations in the gut microbiome may correlate
cases had more unique bacterial co-occurrences. Bacteroides with urinary urgency and incontinence symptoms, under-
and Lactobacillus were central bacteria in controls, whereas scoring the interconnected nature of microbial populations
Aerococcus was central in cases, associating with bacteria across different physiological systems.
commonly linked to bacterial vaginosis. In the bladder, cases The study focuses on exploring the links between the
had fewer network clusters than controls. Lactobacillus was fecal microbiome and fecal incontinence, and the associa-
central in both groups but associated with known uropatho- tion between gut microbiota and sexual desire [35]. This
gens in cases. The overlap of bacterial genera between the research is designed to expand our understanding of the
bladder and vagina was larger in cases (43%) than in controls microbiome's influence, venturing into areas beyond tra-
(29%). In conclusion, the study unveiled a higher overlap in ditional scopes. The employment of advanced techniques,
microbial communities of the bladder and vagina in cases including next-generation sequencing of 16S rRNA genes,
International Urogynecology Journal (2024) 35:1347–1362 1361

targeted metabolic profiling [31], and various comprehen- microbiome modifications on pelvic floor dysfunctions in
sive bioinformatics analyses, has been instrumental in deep- women. The study should focus on establishing a causal
ening our understanding of microbiome behavior [32]. These relationship between specific microbiome changes and the
methodologies have yielded significant insights and laid a development or improvement of pelvic floor conditions.
solid foundation for subsequent research in this domain.
Last, the diversity of microbiome compositions among
Authors’ Contributions G.B.: contributed to the conception and design
individuals and their correlation with disease states highlight of the study, acquisition and analysis of data, drafting of the article,
the potential for personalized treatment approaches. Under- and approved the final version to be published; P.K.: significantly con-
standing and managing an individual's microbiome could tributed to the design of the study, interpretation of data, revising the
become an essential component of their health care manage- article critically for important intellectual content, and final approval
of the version to be published; T.M.: Contributed to the acquisition of
ment. This publication thoroughly addresses a swiftly evolv- data, analysis, drafting and revising the article, and final approval of
ing field of research, beginning to reveal the comprehensive the version to be published; D.B.: assisted in data acquisition, analysis,
and complex role of the microbiome in health maintenance and interpretation, participated in drafting the article, and gave final
and disease development, especially in female urological approval of the version to be published; D.C.: involved in data analysis,
interpretation, critical revision of the article for key intellectual content,
and reproductive health. Through a set of carefully planned and approved the final version to be published.
studies, this research lays a solid foundation for future inves-
tigations aimed at harnessing the microbiome for diagnostic Declarations
and therapeutic innovations.
The aforementioned literature review comprehensively Conflicts of Interest None.
outlines the current state of knowledge regarding the role
of the microbiome in female pelvic floor dysfunction. How-
ever, one research gap that emerges from the review is the
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