Female Urogenital Microbiome in Health and Disease

A special issue of Microorganisms (ISSN 2076-2607). This special issue belongs to the section "Medical Microbiology".

Deadline for manuscript submissions: closed (31 October 2023) | Viewed by 19796

Special Issue Editors


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Guest Editor
UCIBIO/REQUIMTE, Laboratório de Microbiologia, Faculdade de Farmácia, Universidade do Porto, 4050-313 Porto, Portugal
Interests: antimicrobial resistance; virulence; urogenital microbiome; bacteriocins

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Guest Editor
UCIBIO/REQUIMTE, Laboratório de Microbiologia, Faculdade de Farmácia, Universidade do Porto, 4050-313 Porto, Portugal
Interests: urogenital microbiome; bacterial taxonomy; Lactobacillaceae; mobile genetic elements; bacteriocins; antimicrobial resistance
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Special Issue Information

Dear Colleagues,

The knowledge on Female Urogenital Microbiome (FUM), whose discovery defied the decades old belief that the bladder was sterile, is still in its infancy compared to other human niches. Studies conducted so far have revealed that healthy FUM is characterized by a relatively low biomass, interpersonal differences in bacterial load, and diversity and abundance of specific bacteria. In addition, the relationships between changes in bacterial composition and development of urinary disorders or infections have also been addressed, but still need further investigation. The scientific challenge of determining the role of the urinary microbiome in maintaining urinary tract homeostasis or contributing to the development of urinary disorders or infections is still limited by the ability to fully differentiate and functionally characterize the overall microbiome, which also prevents the development of microbiome-based interventions to preserve or restore the microbial community that exists in the human healthy state.

This Special Issue of Microorganisms provides a platform for authors to present novel tools and scientific concepts on the Female Urinary or Vaginal Microbiome in Health and Disease by means of research articles, reviews and editorials.

Dr. Filipa Grosso
Dr. Teresa G Ribeiro
Guest Editors

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Keywords

  • microbiome
  • urinary tract infection
  • urinary disorders
  • bacterial taxonomy
  • Lactobacillaceae
  • bacteriocin
  • antimicrobial resistance
  • virulence
  • 16S rRNA amplicon-sequencing
  • whole-metagenome shotgun sequencing
  • culturomics

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Published Papers (6 papers)

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Research

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12 pages, 2244 KiB  
Article
An Indirect Fluorescence Microscopy Method to Assess Vaginal Lactobacillus Concentrations
by Ângela Lima, Christina A. Muzny and Nuno Cerca
Microorganisms 2024, 12(1), 114; https://doi.org/10.3390/microorganisms12010114 - 5 Jan 2024
Viewed by 1189
Abstract
Lactobacillus species are the main colonizers of the vaginal microbiota in healthy women. Their absolute quantification by culture-based methods is limited due to their fastidious growth. Flow cytometry can quantify the bacterial concentration of these bacteria but requires the acquisition of expensive equipment. [...] Read more.
Lactobacillus species are the main colonizers of the vaginal microbiota in healthy women. Their absolute quantification by culture-based methods is limited due to their fastidious growth. Flow cytometry can quantify the bacterial concentration of these bacteria but requires the acquisition of expensive equipment. More affordable non-culturable methods, such as fluorescence microscopy, are hampered by the small size of the bacteria. Herein, we developed an indirect fluorescence microscopy method to determine vaginal lactobacilli concentration by determining the correlation between surface area bacterial measurement and initial concentration of an easily cultivable bacterium (Escherichia coli) and applying it to lactobacilli fluorescence microscopy counts. In addition, vaginal lactobacilli were quantified by colony-forming units and flow cytometry in order to compare these results with the indirect method results. The colony-forming-unit values were lower than the results obtained from the other two techniques, while flow cytometry and fluorescence microscopy results agreed. Thus, our developed method was able to accurately quantify vaginal lactobacilli. Full article
(This article belongs to the Special Issue Female Urogenital Microbiome in Health and Disease)
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15 pages, 308 KiB  
Article
Presence and Relevance of Emerging Microorganisms in Clinical Genitourinary Samples
by Antonio Rosales-Castillo, Manuela Expósito-Ruiz, Miguel Gutiérrez-Soto, José María Navarro-Marí and José Gutiérrez-Fernández
Microorganisms 2023, 11(4), 915; https://doi.org/10.3390/microorganisms11040915 - 31 Mar 2023
Cited by 2 | Viewed by 1802
Abstract
Microorganisms responsible for genitourinary infections increasingly include species other than conventional etiological agents that are of clinical and pathogenic relevance and therapeutic interest. This cross-sectional descriptive study selected samples from clinical genitourinary episodes between January 2016 and December 2019 in which emerging microbiological [...] Read more.
Microorganisms responsible for genitourinary infections increasingly include species other than conventional etiological agents that are of clinical and pathogenic relevance and therapeutic interest. This cross-sectional descriptive study selected samples from clinical genitourinary episodes between January 2016 and December 2019 in which emerging microbiological agents were detected. The patients’ epidemiological characteristics, clinical presentation, antibiotic treatment, and outcome were studied to identify their pathogenic role. The emerging microorganisms most frequently detected in urinary tract infections were Streptococcus bovis (58.5%) and Gardnerella spp. (23.6%) in females and S. bovis (32.3%), Aerococcus urinae (18.6%), and Corynebacterium spp. (16.9%) in males, while the most frequently detected in genital infections were S. viridans (36.4%) in females and C. glucuronolyticum (32.2%) and Gardnerella spp. (35.6%) in males. All cases in female children were produced by S. bovis. Symptomatic episodes were more frequent with Aerococcus spp. and S. bovis and the presence of leukocytosis more frequent with Aerococcus spp. Quinolones and doxycycline were most often prescribed antibiotics for genital infections and quinolones and amoxicillin-clavulanic acid for urinary infections. Urinary infection by Aerococcus spp. was more frequent in males of advanced age, Corynebacterium spp. was more frequent in permanent vesical catheter carriers, and episodes of asymptomatic bacteriuria by Gardnerella spp. were more frequent in patients with kidney transplant and chronic consumers of corticosteroid therapy. Lactobacillus spp. should be considered in urinary infections of patients of advanced age and with a previous antibiotic load. Genital infection by Gardnerella spp. was significantly associated with a history of risky sexual relations. Full article
(This article belongs to the Special Issue Female Urogenital Microbiome in Health and Disease)
13 pages, 1222 KiB  
Article
Characterization of the Endometrial Microbiome in Patients with Recurrent Implantation Failure
by Francisca Maria Lozano, Belén Lledó, Ruth Morales, Alba Cascales, Mónica Hortal, Andrea Bernabeu and Rafael Bernabeu
Microorganisms 2023, 11(3), 741; https://doi.org/10.3390/microorganisms11030741 - 14 Mar 2023
Cited by 14 | Viewed by 3821
Abstract
An abnormal endometrial microbiota has been associated with implantation failure; therefore, it may be important to evaluate it in order to improve reproductive outcomes in infertile patients. The main objective of our study was to compare the endometrial microbiome of patients with recurrent [...] Read more.
An abnormal endometrial microbiota has been associated with implantation failure; therefore, it may be important to evaluate it in order to improve reproductive outcomes in infertile patients. The main objective of our study was to compare the endometrial microbiome of patients with recurrent implantation failure (RIF) and control patients undergoing assisted reproduction treatment (ART). A prospective cohort study including forty-five patients with their own or donated gametes. The endometrial microbiome was analysed by massive sequencing of the bacterial 16S rRNA gene. Different bacterial communities were detected in RIF and control patients. Lactobacillus stands out as the most frequent genus, with 92.27% in RIF patients and 97.96% in control patients, and significant differences were reported between the two groups (p = 0.002). No significant differences were found regarding alpha diversity index. In beta diversity analysis, a significant trend was observed in the separation of the bacterial community between established groups (p < 0.07). Relative abundance analysis identified genera Prevotella (p < 0.001), Streptococcus (p < 0.001), Bifidobacterium (p = 0.002), Lactobacillus (p = 0.002) and Dialister (p = 0.003). Our results demonstrated the existence of an endometrial microbiota characteristic of RIF patients and showed that there might be a relationship between population of the endometrial microbiome and embryo implantation failure, providing us the possibility to improve clinical results in this patients. Full article
(This article belongs to the Special Issue Female Urogenital Microbiome in Health and Disease)
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16 pages, 332 KiB  
Article
Expanding the Bacterial Diversity of the Female Urinary Microbiome: Description of Eight New Corynebacterium Species
by Elisabete Alves Cappelli, Magdalena Ksiezarek, Jacqueline Wolf, Meina Neumann-Schaal, Teresa Gonçalves Ribeiro and Luísa Peixe
Microorganisms 2023, 11(2), 388; https://doi.org/10.3390/microorganisms11020388 - 3 Feb 2023
Cited by 5 | Viewed by 3191
Abstract
The genus Corynebacterium is frequently found in the female urinary microbiome (FUM). In-depth characterization of Corynebacterium at the species level has been barely exploited. During ongoing FUM research studies, eight strains (c8Ua_144T, c8Ua_172T, c8Ua_174T, c8Ua_181T, [...] Read more.
The genus Corynebacterium is frequently found in the female urinary microbiome (FUM). In-depth characterization of Corynebacterium at the species level has been barely exploited. During ongoing FUM research studies, eight strains (c8Ua_144T, c8Ua_172T, c8Ua_174T, c8Ua_181T, c9Ua_112T, c19Ua_109T, c19Ua_121T, and c21Ua_68T) isolated from urine samples of healthy women or diagnosed with overactive bladder could not be allocated to any valid Corynebacterium species. In this work, we aimed to characterize these strains based on a polyphasic approach. The strains were Gram stain positive, rod to coccoid shaped, nonmotile, catalase positive, and oxidase negative. Phylogenetic analysis based on 16S rRNA and rpoB gene sequences indicated that all strains belonged to the genus Corynebacterium. The average nucleotide identity and digital DNA–DNA hybridization values among the genomes of the above eight strains and closely related type strains of the Corynebacterium genus were <95 (74.1%–93.9%) and <70% (22.2%–56.5%), respectively. Mycolic acids were identified in all strains. MK-8(H2) and/or MK-9(H2) were identified as the major menaquinones. The polar lipids’ pattern mostly consisted of diphosphatidylglycerol, phosphatidylglycerol, and glycophospholipids. The major fatty acid was C18:1ω9c. Corynebacterium lehmanniae (c8Ua_144T = DSM 113405T = CCP 74T), Corynebacterium meitnerae (c8Ua_172T = DSM 113406T = CCP 75T), Corynebacterium evansiae (c8Ua_174T = DSM 113407T = CCP 76T), Corynebacterium curieae (c8Ua_181T = DSM 113408T = CCP 77T), Corynebacterium macclintockiae (c9Ua_112T = DSM 113409T = CCP 78T), Corynebacterium hesseae (c19Ua_109T = DSM 113410T= CCP 79T), Corynebacterium marquesiae (c19Ua_121T = DSM 113411T = CCP 80T), and Corynebacterium yonathiae (c21Ua_68T = DSM 113412T = CCP 81T) are proposed. This study evidenced that commonly used methodologies on FUM research presented limited resolution for discriminating Corynebacterium at the species level. Future research studying the biological mechanisms of the new Corynebacterium species here described may shed light on their possible beneficial role for healthy FUM. Full article
(This article belongs to the Special Issue Female Urogenital Microbiome in Health and Disease)

Review

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18 pages, 1026 KiB  
Review
Current Viewpoint on Female Urogenital Microbiome—The Cause or the Consequence?
by Marina Čeprnja, Edin Hadžić, Damir Oros, Ena Melvan, Antonio Starcevic and Jurica Zucko
Microorganisms 2023, 11(5), 1207; https://doi.org/10.3390/microorganisms11051207 - 4 May 2023
Cited by 2 | Viewed by 3570
Abstract
An increasing amount of evidence implies that native microbiota is a constituent part of a healthy urinary tract (UT), making it an ecosystem on its own. What is still not clear is whether the origin of the urinary microbial community is the indirect [...] Read more.
An increasing amount of evidence implies that native microbiota is a constituent part of a healthy urinary tract (UT), making it an ecosystem on its own. What is still not clear is whether the origin of the urinary microbial community is the indirect consequence of the more abundant gut microbiota or a more distinct separation exists between these two systems. Another area of uncertainty is the existence of a link between the shifts in UT microbial composition and both the onset and persistence of cystitis symptoms. Cystitis is one of the most common reasons for antimicrobial drugs prescriptions in primary and secondary care and an important contributor to the problem of antimicrobial resistance. Despite this fact, we still have trouble distinguishing whether the primary cause of the majority of cystitis cases is a single pathogen overgrowth or a systemic disorder affecting the entire urinary microbiota. There is an increasing trend in studies monitoring changes and dynamics of UT microbiota, but this field of research is still in its infancy. Using NGS and bioinformatics, it is possible to obtain microbiota taxonomic profiles directly from urine samples, which can provide a window into microbial diversity (or the lack of) underlying each patient’s cystitis symptoms. However, while microbiota refers to the living collection of microorganisms, an interchangeably used term microbiome referring to the genetic material of the microbiota is more often used in conjunction with sequencing data. It is this vast amount of sequences, which are truly “Big Data”, that allow us to create models that describe interactions between different species contributing to an UT ecosystem, when coupled with machine-learning techniques. Although in a simplified predator—prey form these multi-species interaction models have the potential to further validate or disprove current beliefs; whether it is the presence or the absence of particular key players in a UT microbial ecosystem, the exact cause or consequence of the otherwise unknown etiology in the majority of cystitis cases. These insights might prove to be vital in our ongoing struggle against pathogen resistance and offer us new and promising clinical markers. Full article
(This article belongs to the Special Issue Female Urogenital Microbiome in Health and Disease)
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14 pages, 1711 KiB  
Review
Alterations of Vaginal Microbiota and Chlamydia trachomatis as Crucial Co-Causative Factors in Cervical Cancer Genesis Procured by HPV
by Ciro Gargiulo Isacco, Mario G. Balzanelli, Stefania Garzone, Mara Lorusso, Francesco Inchingolo, Kieu C. D. Nguyen, Luigi Santacroce, Adriana Mosca and Raffaele Del Prete
Microorganisms 2023, 11(3), 662; https://doi.org/10.3390/microorganisms11030662 - 6 Mar 2023
Cited by 12 | Viewed by 5251
Abstract
Chlamydia trachomatis and human papillomavirus (HPV) are the most common pathogens found in sexually transmitted infections (STIs), and both are known to increase the risk of cervical cancer (CC) and infertility. HPV is extremely common worldwide, and scientists use it to distinguish between [...] Read more.
Chlamydia trachomatis and human papillomavirus (HPV) are the most common pathogens found in sexually transmitted infections (STIs), and both are known to increase the risk of cervical cancer (CC) and infertility. HPV is extremely common worldwide, and scientists use it to distinguish between low-risk and high-risk genotypes. In addition, HPV transmission can occur via simple contact in the genital area. From 50 to 80% of sexually active individuals become infected with both C. trachomatis and HPV viruses during their lifetime, and up to 50% become infected with an HPV oncogenic genotype. The natural history of this coinfection is strongly conditioned by the balance between the host microbiome and immune condition and the infecting agent. Though the infection often regresses, it tends to persist throughout adult life asymptomatically and silently. The partnership between HPV and C. trachomatis is basically due to their similarities: common transmission routes, reciprocal advantages, and the same risk factors. C. trachomatis is a Gram-negative bacteria, similar to HPV, and an intracellular bacterium, which shows a unique biphasic development that helps the latter continue its steady progression into the host throughout the entire life. Indeed, depending on the individual’s immune condition, the C. trachomatis infection tends to migrate toward the upper genital tract and spread to the uterus, and the fallopian tubes open up a pathway to HPV invasion. In addition, most HPV and C. trachomatis infections related to the female genital tract are facilitated by the decay of the first line of defense in the vaginal environment, which is constituted by a healthy vaginal microbiome that is characterized by a net equilibrium of all its components. Thus, the aim of this paper was to highlight the complexity and fragility of the vaginal microenvironment and accentuate the fundamental role of all elements and systems involved, including the Lactobacillus strains (Lactobacillus gasseri, Lactobacillus jensenii, Lactobacillus crispatus) and the immune–endocrine system, in preserving it from oncogenic mutation. Therefore, age, diet, and genetic predisposition together with an unspecific, persistent low-grade inflammatory state were found to be implicated in a high frequency and severity grade of disease, potentially resulting in pre-cancerous and cancerous cervical lesions. Full article
(This article belongs to the Special Issue Female Urogenital Microbiome in Health and Disease)
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