1. bookVolume 58 (2019): Issue 3 (January 2019)
Journal Details
License
Format
Journal
eISSN
2545-3149
First Published
01 Mar 1961
Publication timeframe
4 times per year
Languages
English, Polish
Open Access

Microbiome Of The Women’S Genital System

Published Online: 05 Oct 2019
Volume & Issue: Volume 58 (2019) - Issue 3 (January 2019)
Page range: 227 - 236
Received: 01 Dec 2018
Accepted: 01 Jun 2019
Journal Details
License
Format
Journal
eISSN
2545-3149
First Published
01 Mar 1961
Publication timeframe
4 times per year
Languages
English, Polish
Abstract

The genital system of women has been colonized by various species of microorganisms since the beginning of life. In the postnatal period, the method of birth is important; when a child is born naturally, passing the female genital tract, it acquires bacteria present in the mother’s vagina, and when through the cesarean section, the child’s organism is first colonized by the mother’s skin microbiota and hospital strains. In female newborns during the first days after the natural birth, the presence of Lactobacillus rods, which acidify the vagina, is readily observed. Later, however, they disappear and during the childhood period, the pH of the vagina becomes alkaline. Only in the period of puberty and full puberty, as a result of the increase in the level of estrogen in the female body, the amount of Lactobacillus strains increases and this continues up to the menopause period, when pathogenic strains begin to dominate. The female vagina is home to not only numerous bacteria, but also fungi, including mainly Candida yeast and filamentous fungi at a lower extent. Dysbiosis of the vagina may be caused by the predominance of pathogenic bacteria over Lactobacillus, resulting in bacterial vaginosis or excess of Candida yeast, resulting in candidiasis. An effective method leading to the homeostasis of the female sexual system is the use of vaginal probiotics, which should consist of strains characteristic to a given female population.

1. Introduction. 2. Microbiome of the baby in the prenatal and postnatal period. 3. Lactobacillus genus as the dominant microbiota of the female genital system. 4. Mycobiome of the female vagina. 5. Vaginal probiotics. 6. Summary

Key words

Słowa kluczowe

Introduction

The human body is a unique living environment for many microorganisms characterized by a large diversity of species and genera. Bacteria, fungi, archaea and viruses colonizing the human body are called a microbiota [27]. They are found both on the skin surface and in the entire digestive system, from the oral cavity to the anus, in the upper respiratory tract and the urogenital system. However, most of them inhabit our digestive tract, including their greatest abundance in the large intestine, where in 1 ml of the content there are on average 1012 microbial cells [25, 58]. Currently, the term microbiome refers to the set of genomes of archaea, commensal, symbiotic and pathogenic bacteria and fungi as well as viruses in the human environment. Clarification of this term became possible thanks to the development of molecular biology and genetic engineering, in particular metagenomic sequencing [32, 50, 58]. Acquiring knowledge of the microbiome revealed the presence of many microorganisms that had previously been unknown [27]. The first comprehensive studies of the human microbiome were launched in 2007 by implementing the international Human Microbiome Project (HMP). The project mentioned above concerned microorganisms whose discovery was based on their genomic nucleotide sequences (metagenomes), nucleotide sequences of messenger RNA (metatranscriptome), protein synthesis (metaproteome) and determination of metabolic products (metabolome) [50]. It is reported that the weight of an adult human’s microbiota is approx. 1-1.5 kg [35, 62]. Microorganisms are particularly abundant and multiply in the places of human body secretions and fluids, such as saliva, sweat, urine, tallow, runny nose, vaginal mucus and blood. Among them are microorganisms providing metabolites necessary for the proper functioning of the organism and pathogens, which cause dysbiosis in the human organism, often causing infections, inflammations, viral, bacterial or fungal diseases.

The female vagina is a characteristic microenvironment of the human body. The species diversity of the vaginal microbiota depends on many factors, such as: woman’s age, place of residence (climatic zone), quality and frequency of hygienic procedures, medications applied, e.g. antibiotics, steroids, immunosuppressants or level of hormones, mainly estrogens in the female organism [44]. The predominant group of bacteria colonizing the vagina of healthy women are the rods of Lactobacillus, while among the yeasts the most common are those of the genus Candida. Disorders of the homeostasis of the vaginal microbiota rely mainly on the change in the ratio between lactobacilli and pathogens, in favour of the latter [26, 71]. In order to restore the natural vaginal microbiota, vaginal probiotics consisting of various species of Lactobacillus, isolated from the vagina of healthy women, are used.

Microbiome of the baby in the prenatal and postnatal period

Until recently, it was thought that the intrauterine environment of a child’s life is sterile. However, modern microbiological and genetic tests confirm the existence of microorganisms in a child already in the prenatal period. The source of these microorganisms is the mother’s organism, and her health condition has a big impact on their quality.

During pregnancy, the female body undergoes numerous changes at the hormonal, immunological and metabolic level, necessary for the normal growth and development of the child in the prenatal period [46]. During this time, the levels of secreted hormones: progesterone and estrogens increase rapidly, and complex changes modulating the immune system, protecting the mother and child from infections are observed.

During the prenatal development of the child, the presence of bacteria has been demonstrated in the placenta, amniotic fluid and umbilical cord blood. It was found that the bacterial populations present in the placenta and amniotic fluid are similar and exhibit little diversification. The type Proteobacteria dominated and the main genera were Enterobacter, Escherichia and Shigella. Microorganisms were also detected in meconium, i.e. the first stool of newborns delivered both in the natural way and by caesarean section. There occurred mainly lactic bacteria of the genus Lactobacillus, Bifidobacterium, Leuconostoc and Enterococcus in it, as well as other ones of the genus Streptococcus, Escherichia, Enterobacter, Klebsiella and Bacteroides [38]. It is assumed that the presence of bacteria belonging to the genera: Enterocococcus, Streptococcus, Staphylococcus, Propionibacterium, Lactobacillus and Bifidobacterium in the placenta, amniotic fluid or meconium may be caused by the transition of microorganisms via the bloodstream, which is confirmed by the presence of various bacteria in umbilical cord blood [37]. In addition, in the child’s body in the prenatal period, the presence of microbiota may be the result of swallowing amniotic fluid, which affects the initial colonization of the gastrointestinal tract and skin in children, and in the case of newborn of female sex - colonization of the vagina [63].

The analysis of the composition of the bacteria species identified in meconium, placenta and amniotic fluid showed a high similarity to the species composition of bacteria found in the mouth of mothers. It has been observed that some oral cavity and gum diseases in pregnant mothers increase the risk of premature labour [1]. Therefore, it is important to care for hygiene and prevent periodontal diseases in this group of women. Another reason for the translocation of bacteria into the uterine cavity in pregnant women are prolonged vaginal infections. Aerobic, anaerobic bacteria and yeast-like fungi have also been identified in the uterine cervix. In addition to commensal bacteria of the genus Lactobacillus, pathogenic species: Enterococcus faecalis, Escherichia coli, Streptococcus agalactiae, Staphylococcus aureus, Klebsiella pneumoniae, Eubacterium lentum and yeasts Candida albicans, Candida glabrata, Candida krusei and Saccharomyces cerevisiae were the most commonly isolated [42]. Their presence in the cervical canal leads to serious gynaecological-obstetric complications, including miscarriages, premature births, infections of the amniotic fluid or lesions of the pelvic organs. Thus, intrauterine infections of the foetus and newborn may occur [12, 30, 41].

Among the postnatal factors affecting the microbiome of the newborn, the following are distinguished: the type of delivery (natural or caesarean section), diet (breastfeeding or modified milk), hygiene (sufficient or excessive) and the use or not of the antibiotic therapy or other medications in the first days of the child’s life, e.g. steroids, modifying the composition of the microflora. During natural delivery, the neonate, passing through the mother’s birth canal, has contact with the microflora derived from her vagina, mainly with the lactic fermentation rods of the genus Lactobacillus, which quickly colonise the skin, digestive tract, oral and nasopharyngeal cavity, but also in the case of the female sex, the urogenital tract [35]. That is why in the newborns of female sex, low pH of the vagina is observed during the first 2–3 weeks of life, which results from lactic acid produced by lactobacilli. Later, the pH of the vagina becomes neutral and remains so until puberty. Other bacteria acquired during physiological labour are: Bacteroides, Bifidobacterium, Enterococcus, Blautia, Veillonella, Streptococcus, Planococcus, Escherichia coli, Staphylococcus and Prevotella [20, 34, 59]. In turn, the organism of neonates born via caesarean section is initially colonized mainly by microorganisms typical of the mother’s skin and hospital strains of the genera: Staphylococcus, Streptococcus, Citrobacter, Pseudomonas, Propionibacterium, Proteus, Actinobacter, Klebsiella and E. coli [8, 20, 21, 47]. Infections with some of these bacteria are undoubtedly detrimental to the health of the child and often require applying antibiotic therapy immediately after delivery. Adverse effects of caesarean section on the risk of the occurrence of such diseases in children like: obesity, type I diabetes, celiac disease, asthma or atopy have also been observed [10, 13, 16, 43].

Over time, the differences in the microbiomes of infants born in a different way gradually diminish, however, the first microorganisms acquired during labour can persist up to approx. 6-24 month of life [8, 34, 39]. After delivery, the composition of the infant’s microbiome is shaped depending on the type of feeding. The microbiological profile of the naturally fed infant’s microbiome abounds in various microbial species, including lactic acid bacteria of the genera Lactobacillus, Bifidobacterium, Lactococcus and Enterococcus, which is not observed in artificial and mixed feeding, where a lower phylogenetic diversity occurs [47]. Madan et al. [47] observe a reduction in the number of Lactococcus bacteria in infants being exclusively breast-fed compared to those fed exclusively with modified milk. Other studies indicate that artificial feeding reduces the population size of Bifidobacterium bacteria compared to exclusive breastfeeding. However, the currently applied enrichment of dairy mixtures with prebiotics, such as short-chain galactooligosaccharides and long-chain fructooligosaccharides, increases the overall abundance of Bifidobacterium in infants fed with modified milk [55, 73]. Around the age of two, species and generic biodiversity of a child’s microbiota increases to become more and more similar to an adult human microbiota.

Lactobacillus genus as the dominant microbiota of the female genital system

The mucous membrane of the female vagina is the site where numerous bacteria occur. So far, 37 genera have been identified, i.e.: Anaerococcus, Anaerotruncus, Atopobium, Arcanobacterium, Bacteroides, Bulleidia, Campylobacter, Clostridium, Coriobacterium, Corynebacterium, Dialister, Eggerthella, Enterococcus, Escherichia, Finegoldia, Gardnerella, Gemella, Klebsiella, Lactococcus, Lactobacillus, Lachnospira, Megasphaera, Mobiluncus, Mycoplasma, Parvimonas, Peptostreptococcus, Porphyromonas, Propionibacterium, Prevotella, Peptoniphilus, Rhodobaca, Rhuminococcus, Streptococcus, Sneathia, Staphylococcus, Ureaplasma, Veillonella [40, 64, 67].

The most abundant amongst them are Gram-positive lactobacilli of the genus Lactobacillus which, depending on the physiological condition of the woman, constitute 60 to even 95% of the microorganisms in the vagina of women in Europe or the United States [31]. They compete there for receptors on epithelial cells and nutrients [42]. Lactobacillus bacterium is characterized by the ability to hydrolyse glycogen, a polysaccharide found in the vaginal glands, which, as a result of their action, is hydrolysed to lactic acid. In this way, the vagina becomes acidified to a pH below 4.5, which protects the epithelium against colonization of the reproductive organs by pathogenic bacteria. Other metabolites produced by Lactobacillus bacteria are bacteriocins which exhibit bacteriostatic and bactericidal activity against pathogenic or related strains. Hydrogen peroxide is also produced, which inhibits the growth of catalase-negative and peroxidase-negative bacteria, and protease inhibitors which prevent the growth and propagation of pathogenic yeast Candida albicans.

To date, 25 species of Lactobacillus inhabiting the female vagina have been identified, i.e.: L. acidophilus, L. amylovorus, L. casei, L. crispatus, L. coleohominis, L. debrueckii subsp. bulgaricus, L. fermentum, L. frumenti, L. gasseri, L. gallinarum, L. helveticus, L. iners, L. johnsonii, L. jensenii, L. oris, L. mucoase, L.plantarum, L. paracasei, L. reuteri, L. rhamnosus, L. ruminis, L. sakei, L. salivarius, L. suntoryeus, L. vaginalis [4, 18, 76].

The structure, size and composition of vaginal microbiota depends on genetic and environmental factors and correlates with the geographical place of residence of women, individual predispositions for colonization and hormone levels [24, 63]. It is observed that the abundance of the rods of Lactobacillus is dependent on the amount of glycogen present in the vagina, which depends on the level of estrogens, female sex hormones.

Currently, many strains isolated from the vagina of women living in Europe, America, Asia and Africa have been tested (Table I). Among the species being dominant in the vaginal microbiota of Polish women, the following prevail: L. acidophilus (35%), L. fermentum (30%), L. plantarum (30%), L. delbrueckii (5%), L. rhamnosus (5%) and a small number of L. gasseri and L. casei [56, 68, 69]. In Nigeria, however, the dominant strains are: L. iners (64%), L. gasseri (8.3%), L. plantarum (7.0%), L. suntoryeus (7.0%), L. crispatus (4, 0%), L. rhamnosus (2.7%), L. vaginalis (2.7%), L.fermentum (1.3%), L. helveticus (1.3%) and L. johnsonii (1, 3%) [5].

Bacteria of the genus Lactobacillus isolated from the female vagina in various geographical regions

Lactobacillus speciesCountry/continentReferences
L. acidophilus, L. agilis, L. coleohominis, L. crispatus, L. fermentum, L. gasseri, L. jensenii, L. johnsonii, L. reuteri, L. rhamnosus, L. ruminus, L. salivarius, L. vaginalisBrazil/South America[52]
L. brevis, L. fermentum, L. gasseri, L. salivariusBulgaria/Europe[18]
L. crispatus, L. gasseri, L. iners, L. jensenii, L. vaginalisChina/Asia[36]
L. acidophilus, L. crispatus, L. gasseri, L. iners, L. jensenii, L. rhamnosusIran/Asia[53]
L. aviaries, L. coleohominis, L. crispatus, L. gasseri, L. jensenii, L. iners, L. salivarius, L. vaginalisJapan/Asia[77]
L. crispatus, L. gasseri, L. iners, L. jensenii, L. vaginalisKorea/Asia[45]
L. crispatus, L. gasseri, L. jenseniiGermany/Europe[33]
L. crispatus, L. fermentum, L. gasseri, L. helveticus, L. iners, L. johnsonii, L. plantarum, L. rhamnosus, L. suntoryeus, L. vaginalisNigeria/Africa[5]
L. acidophilus subsp. bulgaricus, L. amylovorus, L. antri, L. casei, L. coleohominis, L. crispatus, L. delbrueckii subsp. bulgaricus, L. fermentum, L. gasseri, L. helveticus, L. jensenii, L. johnsonii, L. paracasei, L. plantarum, L. rhamnosus, L. reuteri, L. sakei, L. salivarius, L. ruminis, L. vaginalisPoland/Europe[19, 56, 68, 69]
L. acidophilus, L. crispatus, L. gasseri, L. helveticus, L. iners, L. jenseniiRussia/Europe[17]
L. crispatus, L. gasseri, L. iners, L. vaginalis, L. jenseniiRwanda/Africa[15]
L. crispatus, L. fermentum, L. gasseri, L. iners, L. jensenii, L. oris, L. reuteri, L. ruminis, L. vaginalisUnited States/North America[4, 75]
L. crispatus, L. gasseri, L. iners, L. jenseniiSweden/Europe[74]
L. acidophilus, L. crispatus, L. delbrueckii, L. gasseri, L. jenseniiSwitzerland/Europe[6]

It has also found that the microbiome of female genital tract during the nine months of pregnancy is subject to significant microbiological changes. It becomes stable and less diverse in terms of species composition, with predominance of the bacteria of the genus Lactobacillus [65]. In the examined pregnant Polish women, the most common species of Lactobacillus colonizing the vagina in the first trimester are: L. crispatus (29%), L. gasseri (19.4%) and L. rhamnosus (16.1%), in the second trimester: L. crispatus (51.6%), L. gasseri (25.8%), L. rhamnosus (19.4%) and L. amylovorus (16.1%), and in the third trimester – L. crispatus (25.8%), L. gasseri (25.8%) and L. johnsonii (19.4%) [19].

Based on the studies of the vaginal microbiota of healthy women in reproductive age from all over the world, the microorganisms occurring in the vagina are classified in V CST (Community State Types) groups [63]. The CST types distinguished: I, II, III and V, are dominated by the following lactic fermentation bacteria: L. crispatus (CST type I), L. gasseri (CST type II), L. iners (CST type III) and L. jensenii (CST type V). The CST IV type includes anaerobic microorganisms such as: Prevotella, Dialister, Atopobium, Gardnerella, Megasphaera, Peptoniphilus, Sneathia, Eggerthella, Aerococcus, Finegoldia and Mobiluncus, among which there is no specific dominant species [63, 76]. In addition, in American studies, including women from different populations, various proportions of CST types were observed depending on the ethnic group (Table II).

Percentage of five types of CST Lactobacillus bacteria in four ethnic groups of women

Ethnic group/ CST %Asians/AsianCaucasian/WhiteBlack African/BlackLatino/Hispanic
Type I2545.422.114.4
Type II5.28.24.87.2
Type III42.726.831.436.1
Type IV19.810.340.438.1
Type V7.39.314.1

It was also observed that the number of Lactobacillus depends on the stage of development and life of women. Initially, in the prenatal period, the presence of various microorganisms was found, which later, in the course of the translocation of the microflora from the mouth and vagina, reach the uterus and colonize the child’s body. These include lactic bacteria of the genera: Lactobacillus, Bifidobacterium, Lactococcus and Leuconostoc [38]. After passing through the mother’s birth canal, abundant in Lactobacillus bacteria, in the female newborns, the pH of the vagina is maintained within 4.8–5.7 for 2–3 weeks, which indicates the activity of lactobacilli. However, already after 3 weeks from giving birth, the pH rises to 6–8 and persists throughout the period of childhood. During pubescence and full maturity in healthy women lactobacilli dominate during the menstrual cycle acidifying the vagina. This is due to the increasing concentration of estrogens in the follicular phase and the increase in glycogen levels. In addition, the presence of α-amylase in the vaginal mucosa supports the breakdown of glycogen into products such as maltose, maltotriose and maltotetraose, which stimulate Lactobacillus spp. to multiply and colonise [49]. However, during menstrual bleeding, the number of Lactobacillus cells decreases periodically, and the pH of the vagina increases to 7.3–7.4. During the premenopausal period, due to decreasing estrogen and glycogen levels and the vaginal mucosa becoming thin, the pH changes in the alkaline direction, and the number of lactic bacteria decreases, which promotes frequent vaginal infections caused by pathogens.

The reduction in the abundance of Lactobacillus bacteria is also influenced by steroid and immunosuppressive drugs, antibiotics and hormonal contraceptives. Steroids imitating female sex hormones, e.g. estrane derivatives, corticosteroids, adrenocortical hormones, have immunosuppressive, anti-inflammatory and antiallergic effects and contribute to reducing the number of Lactobacillus bacteria. Antibiotics, on the other hand, which act bactericidally against Grampositive, also reduce the number of lactobacilli [51]. These are the following antibiotics:

beta-lactam antibiotics: natural, isoxazole and semi-synthetic penicillins, cephalosporins, carbapenems, monobactams, macrolides, lincosamides, fusidic acid;

peptide antibiotics, containing in their composition bacteriocins, i.e. : gramatacin, tirodacin, bacitracin, viomycin, polymyxin;

glycopeptide: vancomycin and teicoplanin;

semi-synthetic lipopeptides, e.g.: daptomycin.

The vaginal microbiota is also influenced by the use of hormonal contraceptives, containing low doses of estrogen, which blocks ovulation and maturation of the endometrium. Thus, the level of glycogen in the vagina is low, resulting in a reduction in the number of Lactobacillus rods. The result thereof are frequent infections of the female vagina: bacterial vaginosis (BV) and vaginal candidiasis.

Mycobiome of the female vagina

The term mycobiome is defined as the sum of genomes and genes belonging to the fungi which inhabit a specific biological niches. The female genital tract, and in particular the vagina, is a specific microenvironment for fungi, to which considerable attention has been paid in the last few years. Molecular technique – NGS sequencing (Next Generation Sequencing) and bioinformatics tools play an important role in understanding the diversity of fungi and are useful in identifying microorganisms and providing a new insight into fungal ecology. Initial studies were based on the techniques of culturing the material obtained through swabs from healthy volunteers or diabetics, teenagers or pregnant women. Fungi were detected in 20–60% of trials [11]. Among them, the yeasts of the genera Candida and Saccharomyces dominated, to a lesser extent there occurred filamentous fungi of the genera Aspergillus, Alternaria and Cladosporium. The presence of these microorganisms depends on the age, hormonal cycle, female health status and the presence of bacteria in the genital tract and specific vaginal environment [11, 14, 50]. Without exception, the dominant member of the fungal community is Candida albicans (85–95% of the Candida population), although there are other species of this genus, e.g. C. krusei, C. parapsilosis, C. tropicalis, C. glabrata, C. guilliermondii, C. pseudotropicalis, C. stellatoidea and others [11, 66]. Guo et al. [29] using the molecular method for identifying the 18S rRNA gene, identified 3 families of fungi: Ascomycota, with the dominant genus of Candida, and Basidiomycota and Oomycota. They also established that women suffering from allergic rhinitis or recurrent vaginal candidiasis had a higher percentage of C. albicans, and lower percentage of S. cerevisiae or other unidentified fungi in comparison with healthy women. In turn, Drell et al. [22], by sequencing a ITS1 fragment of DNA in samples obtained from the vaginas of 294 healthy women in Estonia, established the presence of Ascomycota in 58% of trials, and Basidiomycota in only 3% of trials. Within the type Ascomycetes the researchers have detected representatives of the orders Saccharomycetales (mainly the genus Candida), Capnodiales, Eurotiales, Pleosporales and Helotiales. C. albicans was detected in 68% of sequenced samples, while many sequences were not systematically assigned due to limited resources of available databases connected with sequencing fungi. On the other hand, in the studies by Bitew and Abebaw [9] in samples of swabs obtained from 210 women in Ethiopia, the following yeasts were identified C. albicans in 58.6% of isolates, C. krusei in 17.2%, C. dubliniensis in 9.2%, C. glabrata in 3.4 % and C. inconspicua, C. tropicalis, C. kefir, C. guiiliermondii, C. lusitaniae and C. parapsilosis in individual cases. The researchers used an automated, compact Vitek 2 system for identification, based on fluorescent detection of yeast growth and metabolic changes occurring in microwells of special cards placed in an incubator connected to the reader [9]. Similar results were obtained in the study of vaginal swabs from women in Saudi Arabia, using various identification methods, where the dominant species in both diseased and healthy women was C. albicans, followed by C. dublinienesis and C. glabrata; while C. tropicalis was found only in diseased women [2]. In turn, in studies conducted in Egypt in 62.7% of samples of swabs from women with symptoms of candidiasis Candida yeasts were found, of which 81.1% were C. albicans, 8.1% C. glabrata and C. tropicalis and 2.7% S. cerevisiae [66].

Yeasts enter the human organism from the natural environment and can be transferred to newborns during labour, colonizing specific human body niches. Ward et al. [72] conducted research on the development of mycobiome in infants in the first months of life, depending on the method of delivery. They found that dominant species in samples obtained from various parts of the body of infants (skin, mouth, anus) were C. parapsilosis, C. tropicalis, S. cerevisiae, C. albicans, C. othopsilosis, Cryptococcus pseudolongus, Cladosporium velox, Debaryomyces rhenium, D. hansenii, Hanseniaspora uvarum, and C. krusei. On the other hand, the composition of the vaginal mycobiome of the women giving birth was dominated by C. albicans, while in the mycobiome of the anus C. albicans, S. cerevisiae, and C. parapsilosis were the most numerous. The overall numbers of detected taxa were similar in the samples obtained from infants and women. Researchers established that the way the children were delivered had an effect on the number of species, but not on the structure of the fungal population. Naturally born infants did not exhibit a greater similarity of the skin mycobiome to their mother’s vaginal mycobiome than the neonates born by caesarean section. However, the difference was visible in the number of C. albicans, which occurred in a significantly higher number on the skin of 1-month-old infants born naturally in comparison to the infants born by caesarean section [72].

There is more and more evidence indicating that estrogens have a positive effect on the colonization of the vaginal mucosa and subsequent infection caused by Candida yeast. Some Candida species possess estrogen receptors. It has been demonstrated that estrogen interferes with the chemotaxis of neutrophils to the vaginal epithelium and inhibits Th17 lymphocytes differentiation, which consequently can lead to an increased susceptibility of the host to the pathogens of the genus Candida. Some reports link symptomatic vaginosis to the luteal phase just before menstruation, when high estrogen level is observed, as well as an increase in vaginal pH level, which additionally facilitates its colonization by the pathogenic yeasts. It has also been proven that Candida can metabolise lactate derived from lactic acid produced by lactic bacteria in the vagina and it has been shown that in the presence of lactic acid C. albicans is less efficiently attacked by macrophages and can change the profiles of immune cell cytokines by raising the production of interleukin 10 (IL-10) and lowering IL-17. Studies confirm that Candida can evolve to stop the immune response and increase the area of its commensalism.

The initial adhesion of yeast to epithelial cells is regulated by hydrophobic interactions between surfaces. The attachment of yeast to the epithelial cell receptors is mediated by adhesion proteins [11, 14]. High capacity of yeasts for adhesion to epithelial cells obtained from women suffering from recurrent candidiasis of vulva and vagina (VVC – VulvoVaginal Candidiasis) has been demonstrated. It is estimated that 3 out of 4 women have been infected with candidiasis at least once in their lifetime, and 20% of healthy women may also be asymptomatic carriers that have been infected with this microorganism in commensal interactions. There exists a view whereby the predispositions for being colonised by Candida are niche-dependent, but they also depend on host immune defects, interrupted vaginal epithelium and microbiological dysbiosis. A statistically significant increase in the number of C. albicans pathogenic yeasts is observed in women with VVC compared to the number of these microorganisms in healthy women, while no significant differences have been observed in the number of Candida yeasts not belonging to the albicans species. These observations confirm the theory of “fungal burden threshold”, above which inflammatory cells occur, whose metabolites are the direct cause of the symptoms of vaginal infection, such as itching, irritation, burning and the appearance of secretions. Candida is a polymorphic fungus in which morphogenic transitions are also part of the pathogenicity mechanism. The yeast form is associated with asymptomatic colonization, transmission and spreading especially through the circulatory system, while the mycelial form is associated with adhesion and mucosal invasion, characteristic for disease symptoms, and the production of agents that cause macrophage lysis [11]. Morphogenesis, however, depends on various factors, including the activity of macrophages, the presence of bacteria and their metabolites in the vagina and estrogen levels [14].

C. albicans virulence factors include extracellular hydrolytic enzymes, heat shock proteins and factors leading to biofilm production. In vitro studies of the proteolytic activity of C. albicans isolates from women with VVC have shown increased activity of enzymes, especially from the aspartic protease family, which are virulence factors disturbing the continuity of the mucosa and inducing immunopathology. Yeast also produces several extracellular enzymes, such as phospholipases, lipases and haemolysins, essential for tissue invasion and nutrient uptake, especially iron released from haemoglobin degradation [14]. Another hypothesis on the pathogenicity of C. albicans is associated with the secretion of toxins. Moyes et al. [54], using a mouse model of oropharyngeal candidiasis, identified a cytolytic peptide toxin, candidalysin, essential for the pathogenesis of the mucosa. Another pathogenic feature of C. albicans is the ability to create a biofilm in contact with, e.g. mucous membranes, followed by the production of hyphae capable of penetrating host tissues. C. albicans biofilm is formed by polysaccharides such as α-mannan, α-1,6 glucan and α-1,3 glucan. The ability to form biofilms is also demonstrated by C. glabrata, C. guilliermondii, C. parapsilosis, and C. tropicalis. All of the above species are capable of creating an invasive hyphal form. In the context of triggering candidiasis, biofilms have been reported to be up to 1000-fold more resistant to antifungal agents used in the treatment, compared to the cells that do not form biofilms [14].

An important issue is an interaction between the bacteria found in the vagina, mainly the rods of Lactobacillus and the pathogenic Candida yeasts. In general, there are 5 ways of fungi-bacteria interaction that can also be present in the vagina, i.e. physical interactions, chemical changes, metabolic by-products, environmental changes and changes in the host’s immune resistance [61]. The most reliable hypothesis regarding these interactions is that the bacteria found in the vagina do not prevent the mucosa colonizing from Candida, but only limit the excessive growth of yeasts, among others through the production of lactate and short-chain fatty acids inhibiting the passage of the pathogen from the cellular stage to the hyphal one [11]. In addition, women with VVC have a less abundant Lactobacillus population. An additional factor influencing the disruption of balance between bacteria and yeasts is antibiotic therapy, but no unequivocal correlation between taking antibiotics and the incidence of VVC has been proven [11]. Another hypothesis is that the hydrogen peroxide secreted by Lactobacillus bacteria is involved in the prevention of adhesion to epithelial cells and is responsible for the control of Candida growth, in addition to other mechanisms associated with the activity of lactobacilli which are not fully understood yet [14]. Mutual interactions of these microbial groups are also dependent on the formation of a multispecies biofilm on the mucous membrane surface. In vitro studies have confirmed the negative impact of Lactobacillus on the formation of mycelium and the suppression of genes responsible for this process [11]. Research into mutual interactions of lactic acid bacteria and yeasts is still continuing and very much needed in the context of VVC prevention and treatment.

Characteristics of the human mycobiome is important for the development of diagnostics and preventive measures in fungal diseases, including vaginal candidiasis.

Vaginal probiotics

Female vaginal microbiota disorders are most often caused by a decrease in the number of lactobacilli to the advantage of pathogenic microorganisms. This results in various types of infections, i.e. bacterial vaginosis and vaginal candidiasis [7, 57, 60]. Vaginal homeostasis disorders are caused by antibiotics, steroid and immunosuppressive drugs, as well as hormonal and barrier contraceptive agents such as condoms, caps and vaginal diaphragms which damages the vaginal epithelium. Other factors with poorly understood mechanism of influencing the vaginal microbiota are: poor hygiene, use of underwear made of synthetic materials, vaginal irrigation, weakening of the immune system as a result of systemic infection or chronic diseases or stress, use of tampons, sexual intercourse or even swimming in a pool during which some rods of Lactobacillus may be partially washed out [50]. Therefore, it is important to quickly restore the original state of the microbiota in this part of the female body by using live cultures of lactic acid bacteria in the form of vaginal probiotics. These are microorganisms which favourably influence the vaginal microbiota by combating the pathogens which are present there. They should meet the criteria set in 2001 and 2002 by the European Food Safety Authority (EFSA) and the World Health Organization (WHO) [28].

Among the basic requirements for vaginal probiotics the following are listed:

being derived from the urogenital system of young women;

accurate genetic, biochemical and morphological identification of the strain;

clinically proven ability to colonize the female vagina;

antagonistic activity against pathogenic bacteria causing infections of the urogenital system;

strong adherence to the vaginal epithelium;

confirmed reduction of the adhesion of pathogens to the vaginal epithelium;

specific resistance to antibiotics for a given species [33].

It has been demonstrated that the use of the L. acidophilus probiotic strains for 6–12 days and L. rhamnosus GR-1, L. fermentum RC-1 for 2 months inhibits the growth of the bacteria causing BV. This is the result of producing hydrogen peroxide, lactic acid, bacteriocins and the inhibition of the adherence of G. vaginalis [23].

Polish studies have demonstrated that oral administration of three specific strains: L. gasseri, L. fermentum and L. plantarum to women of reproductive age, increased the number of Lactobacillus rods in the anus and vagina of the patients. At the same time, a decrease in vaginal pH and an effective change in the Nugent scale values has been observed, which is used to assess the vaginal biocenosis based on proportional shares of particular types of bacteria in the preparation tested. However, the use of probiotic is not always effective, especially when the urogenital tract infection is very advanced [70]. In addition, it was found that other species of Lactobacillus, which are not the natural, native microbiota of the vaginal epithelium, cannot colonize intimate areas permanently. They occur only locally during the application of the probiotic, and after the end of supplementation they die and are excreted from the body. According to the data published in the journal Nature [48], the immune system ultimately determines what the quantitative and qualitative composition of the microbiota of our body will be. This is confirmed by the studies in which a vaginal probiotic containing L. rhamnosus strain was used by women who live in the United States. On the third day of the experiment, the strain was characterized by a high titre but on the 21st day it was barely detectable. The supplemented microorganism was not identified as a typical, native microbiota of the genital tract of American women. It was only a temporary colonizer. The authors suggest that the elimination of the L. rhamnosus probiotic strain occurred due to the natural self-regulating mechanisms of the vaginal ecosystem [3].

Vaginal probiotics available on the pharmaceutical market are in the form of freeze-dried cellular biomass immobilized in hard cellulose or gelatine capsules. The frequency of their application depends on the severity of infection resulting from vaginal microbiota disorders. They can colonize the vagina or stay there long enough to cause the restoration of native, natural microbiota. For this purpose, they must produce L (+) lactic acid in an amount of more than 50% of the total amount of acid produced and possibly other organic acids, such as acetic, formic, propionic, benzoic or mevalonic acid. They should have the ability to adhere to the vaginal epithelium, which requires testing their hydrophobic properties, surface charge, surface structure and affinity for the epithelial cell receptors.

Summary

Knowledge and understanding of the functioning of the female reproductive system microbiota is important in the treatment and prevention of vaginal infection. The more so because they are often chronic and difficult to treat, which constitutes a contemporary challenge in urology and gynaecology. In particular, vaginosis and candidiasis which occur in pregnant women require treatment due to the risk of miscarriages and intrauterine infections. More and more knowledge about the role of probiotic bacteria in the treatment of vaginal infections allows the search for new, effective strains. It is important that they have GRAS (generally recognized as safe) status, i.e. they are non-pathogenic and do not produce toxic, carcinogenic, teratogenic and mutagenic substances. In addition, they should survive the technological process and storage period in dry and refrigerated conditions for 12 to 24 months. All the more so because during production, the bacteria are most often subjected to the freeze-drying process (lyophilization), which allows for obtaining permanent preparations which preserve their viability. In addition, a probiotic preparation which is a medicine should be manufactured in accordance with good manufacturing practice (GMP) and be appropriately labelled. There is a great need to compose new vaginal probiotics on the Polish market, which is deficient in preparations based on native Lactobacillus bacteria strains.

Percentage of five types of CST Lactobacillus bacteria in four ethnic groups of women

Ethnic group/ CST %Asians/AsianCaucasian/WhiteBlack African/BlackLatino/Hispanic
Type I2545.422.114.4
Type II5.28.24.87.2
Type III42.726.831.436.1
Type IV19.810.340.438.1
Type V7.39.314.1

Bacteria of the genus Lactobacillus isolated from the female vagina in various geographical regions

Lactobacillus speciesCountry/continentReferences
L. acidophilus, L. agilis, L. coleohominis, L. crispatus, L. fermentum, L. gasseri, L. jensenii, L. johnsonii, L. reuteri, L. rhamnosus, L. ruminus, L. salivarius, L. vaginalisBrazil/South America[52]
L. brevis, L. fermentum, L. gasseri, L. salivariusBulgaria/Europe[18]
L. crispatus, L. gasseri, L. iners, L. jensenii, L. vaginalisChina/Asia[36]
L. acidophilus, L. crispatus, L. gasseri, L. iners, L. jensenii, L. rhamnosusIran/Asia[53]
L. aviaries, L. coleohominis, L. crispatus, L. gasseri, L. jensenii, L. iners, L. salivarius, L. vaginalisJapan/Asia[77]
L. crispatus, L. gasseri, L. iners, L. jensenii, L. vaginalisKorea/Asia[45]
L. crispatus, L. gasseri, L. jenseniiGermany/Europe[33]
L. crispatus, L. fermentum, L. gasseri, L. helveticus, L. iners, L. johnsonii, L. plantarum, L. rhamnosus, L. suntoryeus, L. vaginalisNigeria/Africa[5]
L. acidophilus subsp. bulgaricus, L. amylovorus, L. antri, L. casei, L. coleohominis, L. crispatus, L. delbrueckii subsp. bulgaricus, L. fermentum, L. gasseri, L. helveticus, L. jensenii, L. johnsonii, L. paracasei, L. plantarum, L. rhamnosus, L. reuteri, L. sakei, L. salivarius, L. ruminis, L. vaginalisPoland/Europe[19, 56, 68, 69]
L. acidophilus, L. crispatus, L. gasseri, L. helveticus, L. iners, L. jenseniiRussia/Europe[17]
L. crispatus, L. gasseri, L. iners, L. vaginalis, L. jenseniiRwanda/Africa[15]
L. crispatus, L. fermentum, L. gasseri, L. iners, L. jensenii, L. oris, L. reuteri, L. ruminis, L. vaginalisUnited States/North America[4, 75]
L. crispatus, L. gasseri, L. iners, L. jenseniiSweden/Europe[74]
L. acidophilus, L. crispatus, L. delbrueckii, L. gasseri, L. jenseniiSwitzerland/Europe[6]

Aagaard K., Ma J., Antony KM., Ganu R., Petrosino J., Versalovic J.: The placenta harbors a unique microbiome. Sci. Transl. Med. 6, 237–265 (2014)AagaardK.MaJ.AntonyKM.GanuR.PetrosinoJ.VersalovicJ.The placenta harbors a unique microbiomeSci. Transl. Med.6237265201410.1126/scitranslmed.3008599492921724848255Search in Google Scholar

Ameen F., Moslem M., Tami M.Al., Al-Ajlan H., Al-Qahtami N.: Identification of Candida species in vaginal flora using conventional and molecular methods. J. Mycologie Medicale 27, 364–368 (2017)AmeenF.MoslemM.TamiM.Al.Al-AjlanH.Al-QahtamiN.Identification of Candida species in vaginal flora using conventional and molecular methodsJ. Mycologie Medicale27364368201710.1016/j.mycmed.2017.04.10528578925Search in Google Scholar

Antonio M.A., Meyn L.A., Murray P.J., Busse B., Hillier S.L.: Vaginal colonization by probiotic Lactobacillus crispatus CTV-05 is decreased by sexual activity and endogenous Lactobacilli. J. Infect. Dis. 199, 1506–1513 (2009)AntonioM.A.MeynL.A.MurrayP.J.BusseB.HillierS.L.Vaginal colonization by probiotic Lactobacillus crispatus CTV-05 is decreased by sexual activity and endogenous LactobacilliJ. Infect. Dis.19915061513200910.1086/59868619331578Search in Google Scholar

Antonio M.A., Hawes S.E., Hillier S.L.: The identification of vaginal Lactobacillus species and demographic and microbiologic characteristics of women colonized by these species. J. Infect. Dis. 180, 1950–1956 (1999)AntonioM.A.HawesS.E.HillierS.L.The identification of vaginal Lactobacillus species and demographic and microbiologic characteristics of women colonized by these speciesJ. Infect. Dis.18019501956199910.1086/31510910558952Search in Google Scholar

Anukam K.C., Osazuwa E.O., Ahonkhai I., Reid G.: 16S rRNA gene sequence and phylogenetic tree of Lactobacillus species from the vagina of healthy Nigerian women. Afr. J. Biotechnol. 4, 1222–1227 (2005)AnukamK.C.OsazuwaE.O.AhonkhaiI.ReidG.16S rRNA gene sequence and phylogenetic tree of Lactobacillus species from the vagina of healthy Nigerian womenAfr. J. Biotechnol.4122212272005Search in Google Scholar

Atassi F., Brassart D., Grob P., Graf F., Servin A.L.: Lactobacillus strains isolated from the vaginal microbiota of healthy women inhibit Prevotella bivia and Gardnerella vaginalis in coculture and cell culture. FEMS Immunol. Med. Microbiol. 48, 424–432 (2006)AtassiF.BrassartD.GrobP.GrafF.ServinA.L.Lactobacillus strains isolated from the vaginal microbiota of healthy women inhibit Prevotella bivia and Gardnerella vaginalis in coculture and cell cultureFEMS Immunol. Med. Microbiol.48424432200610.1111/j.1574-695X.2006.00162.x17059467Search in Google Scholar

Atassi F., Brassart D., Grob P., Graf F., Servin A.L.: Vaginal Lactobacillus isolates inhibit uropathogenic Escherichia coli. FEMS Microbiol. Lett. 257, 132–138 (2006)AtassiF.BrassartD.GrobP.GrafF.ServinA.L.Vaginal Lactobacillus isolates inhibit uropathogenic Escherichia coliFEMS Microbiol. Lett.257132138200610.1111/j.1574-6968.2006.00163.x16553843Search in Google Scholar

Bäckhed F.: Dynamics and stabilization of the human gut microbiome during the first year of life. Cell Host Microbe 17, 690–703 (2015)BäckhedF.Dynamics and stabilization of the human gut microbiome during the first year of lifeCell Host Microbe17690703201510.1016/j.chom.2015.04.00425974306Search in Google Scholar

Bitew A., Abebaw Y.: Vulvovaginal candidiasis: species distribution of Candida and their antifungal susceptibility pattern. BMC Women’s Health 18, 94 (2018)BitewA.AbebawY.Vulvovaginal candidiasis: species distribution of Candida and their antifungal susceptibility patternBMC Women’s Health1894201810.1186/s12905-018-0607-z600318829902998Search in Google Scholar

Blustein J., Attina T., Liu M., Ryan A.M., Cox L.M., Blaser M.J., Trasande L.: Association of caesar ean delivery with child adiposity from age 6 weeks to 15 years. Int. J. Obesity 37, 900–906 (2013)BlusteinJ.AttinaT.LiuM.RyanA.M.CoxL.M.BlaserM.J.TrasandeL.Association of caesar ean delivery with child adiposity from age 6 weeks to 15 yearsInt. J. Obesity37900906201310.1038/ijo.2013.49500794623670220Search in Google Scholar

Bradford L.L., Ravel J.: The vaginal mycobiome: A contemporary perspective on fungi in women’s health and diseases. Virulence 8, 342–351 (2017)BradfordL.L.RavelJ.The vaginal mycobiome: A contemporary perspective on fungi in women’s health and diseasesVirulence8342351201710.1080/21505594.2016.1237332541124327657355Search in Google Scholar

Brook I.: Bacteremia and septicemia due to anaerobic bacteria in newborns. J. Neonatal Perinatal Med. 1, 201–208 (2008)BrookI.Bacteremia and septicemia due to anaerobic bacteria in newbornsJ. Neonatal Perinatal Med.12012082008Search in Google Scholar

Cardwell C.R., Patterson C.C. et al.: Caesarean section is associated with an increased risk of childhood-onset type 1 diabetes mellitus: a meta-analysis of observational studies. Diabetology 51, 726–735 (2008)CardwellC.R.PattersonC.C.Caesarean section is associated with an increased risk of childhood-onset type 1 diabetes mellitus: a meta-analysis of observational studiesDiabetology51726735200810.1007/s00125-008-0941-z18292986Search in Google Scholar

Cauchie M., Desmet S., Lagrou K.: Candida and its dual lifestyle as a commensal and a pathogen. Res. Microbiol. 168, 802–810 (2017)CauchieM.DesmetS.LagrouK.Candida and its dual lifestyle as a commensal and a pathogenRes. Microbiol.168802810201710.1016/j.resmic.2017.02.00528263903Search in Google Scholar

Crucitti T., Hardy L., van de Wijgert J., Agaba S., Buyze J., Kestelyn E., Delvaux T., Mwambarangwe L., De Baetselier I., Jespers V.: Contraceptive rings promote vaginal lactobacilli in a high bacterial vaginosis prevalence population: A randomised, open-label longitudinal study in Rwandan women. Plos One 13, e0201003 (2018)CrucittiT.HardyL., van de WijgertJ.AgabaS.BuyzeJ.KestelynE.DelvauxT.MwambarangweL.De BaetselierI.JespersV.Contraceptive rings promote vaginal lactobacilli in a high bacterial vaginosis prevalence population: A randomised, open-label longitudinal study in Rwandan womenPlos One13e0201003201810.1371/journal.pone.0201003605603630036385Search in Google Scholar

Decker E., Engelmann G., Findeisen A., Gerner P., Laaß M., Ney D., Posovszky C., Hoy L., Hornef M.W.: Cesarean delivery is associated with celiac disease but not inflammatory bowel disease in children. Pediatr. 125, 1433–1440 (2010)DeckerE.EngelmannG.FindeisenA.GernerP., Laaß M., NeyD.PosovszkyC.HoyL.HornefM.W.Cesarean delivery is associated with celiac disease but not inflammatory bowel disease in childrenPediatr.12514331440201010.1542/peds.2009-226020478942Search in Google Scholar

Demkin V.V., Koshechkin S.I.: Characterization of vaginal Lactobacillus species by rplK – based multiplex qPCR in Russian women. Anaerobe 47, 1–7 (2017)DemkinV.V.KoshechkinS.I.Characterization of vaginal Lactobacillus species by rplK – based multiplex qPCR in Russian womenAnaerobe4717201710.1016/j.anaerobe.2017.03.01128315382Search in Google Scholar

Dimitonova S.P., Bakalov B.V., Aleksandrova-, Georgieva R.N., Danova S.T.: Phenotypic and molecular identification of lactobacilli isolated from vaginal secretions. J. Microbiol. Immunol. Infect. 41, 469–77 (2008)DimitonovaS.P.BakalovB.V., Aleksandrova-, GeorgievaR.N.DanovaS.T.Phenotypic and molecular identification of lactobacilli isolated from vaginal secretionsJ. Microbiol. Immunol. Infect.41469772008Search in Google Scholar

Dobrut A., Gosiewski T., Pabian W., Bodaszewska-Lubas M., Ochonska D., Buland M., Brzychczy-Wloch M.: The dynamics of vaginal and rectal Lactobacillus spp. flora in subsequent trimesters of pregnancy in healthy Polish women, assessed using the Sanger sequencing method. BMC Pregnancy and Childbirth 18, 350 (2018)DobrutA.GosiewskiT.PabianW.Bodaszewska-LubasM.OchonskaD.BulandM.Brzychczy-WlochM.The dynamics of vaginal and rectal Lactobacillus spp. flora in subsequent trimesters of pregnancy in healthy Polish women, assessed using the Sanger sequencing methodBMC Pregnancy and Childbirth18350201810.1186/s12884-018-1987-7611425530157784Search in Google Scholar

Dominguez-Bell M.G., Costello E.K., Contreras M., Magris M., Hidalgo G., Fierer N., Knight R.: Delivery mode shapes the acquisition and structure of the initial microbiota across multiple body habitats in new borns. Proc. Natl Acad. Sci. USA 107, 11971–11975 (2010)Dominguez-BellM.G.CostelloE.K.ContrerasM.MagrisM.HidalgoG.FiererN.KnightR.Delivery mode shapes the acquisition and structure of the initial microbiota across multiple body habitats in new bornsProc. Natl Acad. Sci. USA1071197111975201010.1073/pnas.1002601107290069320566857Search in Google Scholar

Dominguez-Bello M.G., Clementem J.C. et al.: Partial restoration of the microbiota of cesarean-born infants via vaginal microbial transfer. Nat. Med. 22, 250–253 (2016)Dominguez-BelloM.G.ClementemJ.C.Partial restoration of the microbiota of cesarean-born infants via vaginal microbial transferNat. Med.22250253201610.1038/nm.4039506295626828196Search in Google Scholar

Drell T., Lillsaar T., Tummeleht L., Simm J., Aaspollou A., Vain E., Saarma I., Saluments A., Donders G.G., Metsis M.: Characterization of the vaginal micro- and mycobiome in asympthomatic reproductive-age Estonian women. Plos One 8, e54379 (2013)DrellT.LillsaarT.TummelehtL.SimmJ.AaspollouA.VainE.SaarmaI.SalumentsA.DondersG.G.MetsisM.Characterization of the vaginal micro- and mycobiome in asympthomatic reproductive-age Estonian womenPlos One8e54379201310.1371/journal.pone.0054379355315723372716Search in Google Scholar

Falagas M.E., Bersi G.I., Athanasiou S.: Probiotics for the treatment of women with bacterial vaginosis. Clin. Microbiol. Infect. 13, 657–664 (2007)FalagasM.E.BersiG.I.AthanasiouS.Probiotics for the treatment of women with bacterial vaginosisClin. Microbiol. Infect.13657664200710.1111/j.1469-0691.2007.01688.x17633390Search in Google Scholar

Fettweis J.M., Brooks J.P., Serrano M.G., Sheth N.U., Girerd P.H., Edwards D.J., Strauss J.F., Jefferson K.K., Buck G.A.: Differences in vaginal microbiome in African-American women versus women of European ancestry. Microbiology 160, 2272–2282 (2014)FettweisJ.M.BrooksJ.P.SerranoM.G.ShethN.U.GirerdP.H.EdwardsD.J.StraussJ.F.JeffersonK.K.BuckG.A.Differences in vaginal microbiome in African-American women versus women of European ancestryMicrobiology16022722282201410.1099/mic.0.081034-0417832925073854Search in Google Scholar

Gill S.R., Pop M., Deboy R.T., Eckburg P.B.: Metagenomic analysis of the human distal gut microbiome. Science 312, 1355–1359 (2006)GillS.R.PopM.DeboyR.T.EckburgP.B.Metagenomic analysis of the human distal gut microbiomeScience31213551359200610.1126/science.1124234302789616741115Search in Google Scholar

Gratacos E., Figueras F., Barranco M., Ros R., Andreu A., Alonso PL., Cararach V.: Prevalence of bacterial vaginosis and correlation of clinical to Gram strain diagnostic criteria in low risk pregnant women. Eur. J. Epidemiol. 15, 913–916 (1999)GratacosE.FiguerasF.BarrancoM.RosR.AndreuA.AlonsoPL.CararachV.Prevalence of bacterial vaginosis and correlation of clinical to Gram strain diagnostic criteria in low risk pregnant womenEur. J. Epidemiol.15913916199910.1023/A:1007673531595Search in Google Scholar

Gregorczyk-Maślanka K., Kurzawa R.: Mikrobiota organizmu ludzkiego i jej wpływ na homeostazę immunologiczną – część I. Alerg. Astma Immun. 21, 146–150 (2016)Gregorczyk-MaślankaK.KurzawaR.Mikrobiota organizmu ludzkiego i jej wpływ na homeostazę immunologiczną – część IAlerg. Astma Immun.211461502016Search in Google Scholar

Guidelines for the Evaluation of Probiotics in Food. Raport a Joint FAO/WHO Working Group, London, Ontario, Canada, (2002)Guidelines for the Evaluation of Probiotics in Food. Raport a Joint FAO/WHO Working Group, London, Ontario, Canada2002Search in Google Scholar

Guo R., Zheng N., Lu H., Yin H., Yao J., Chen Y.: Increased diversity of fungal flora in the vagina of patients with recurrent vaginal candidases and allergic rhinitis. Microb. Ecol. 64, 918–927 (2012)GuoR.ZhengN.LuH.YinH.YaoJ.ChenY.Increased diversity of fungal flora in the vagina of patients with recurrent vaginal candidases and allergic rhinitisMicrob. Ecol.64918927201210.1007/s00248-012-0084-022767123Search in Google Scholar

Heczko P.B., Niemiec T.: Zalecenia dotyczące wykazywania nosicielstwa paciorkowców grupy B (GBS) u kobiet w ciąży i zapobiegania zakażeniom u noworodków spowodowanym przez ten drobnoustrój. Zakażenia 2, 87–96 (2008)HeczkoP.B.NiemiecT.Zalecenia dotyczące wykazywania nosicielstwa paciorkowców grupy B (GBS) u kobiet w ciąży i zapobiegania zakażeniom u noworodków spowodowanym przez ten drobnoustrójZakażenia287962008Search in Google Scholar

Hillier S., Arko S.: Vaginal infection (in) Atlas of sexually transmitted diseases and AIDS, red. S.A. Morse, A.A. Moreland, K.K. Holmes, Mosby-Wolfe, Baltimore, 1996, s. 79–94HillierS.ArkoS.Vaginal infection (in) Atlas of sexually transmitted diseases and AIDSred.MorseS.A.MorelandA.A.HolmesK.K.Mosby-WolfeBaltimore1996s.7994Search in Google Scholar

Hoopper L.V., Gordon J.I.: Commensal host-bacterial relationships in the gut. Science 292, 1115–1118 (2001)HoopperL.V.GordonJ.I.Commensal host-bacterial relationships in the gutScience29211151118200110.1126/science.105870911352068Search in Google Scholar

Hütt P., Mändar R. et al.: Characterisation of probiotic properties in human vaginal lactobacilli strains. Microb. Ecol. Health Dis. 27, 30484 (2016)HüttP.MändarR.Characterisation of probiotic properties in human vaginal lactobacilli strainsMicrob. Ecol. Health Dis.2730484201610.3402/mehd.v27.30484498561727527701Search in Google Scholar

Jakobsson H.E., Abrahamsson T.R., Jenmalm M.C. et al.: Decreased gut microbiota diversity, delayed Bacteroidetes colonisation and reduced Th1 responses in infants delivered by caesarean section. Gut 63, 559–566 (2014)JakobssonH.E.AbrahamssonT.R.JenmalmM.C.Decreased gut microbiota diversity, delayed Bacteroidetes colonisation and reduced Th1 responses in infants delivered by caesarean sectionGut63559566201410.1136/gutjnl-2012-30324923926244Search in Google Scholar

Jaworski A., Dudek K., Jurczak I.: Struktura i rola biologiczna mikrobioty przewodu pokarmowego człowieka zdrowego i w chorobie. J. Health Study Med. 4, 37–61 (2016)JaworskiA.DudekK.JurczakI.Struktura i rola biologiczna mikrobioty przewodu pokarmowego człowieka zdrowego i w chorobieJ. Health Study Med.437612016Search in Google Scholar

Jespers V., Crucitti T. et al.: The significance of Lactobacillus crispatus and L. vaginalis for vaginal health and the negative effect of recent sex: a cross-sectional descriptive study across groups of African women. BMC Infectious Diseases 15, 115 (2015)JespersV.CrucittiT.The significance of Lactobacillus crispatus and L. vaginalis for vaginal health and the negative effect of recent sex: a cross-sectional descriptive study across groups of African womenBMC Infectious Diseases15115201510.1186/s12879-015-0825-z435194325879811Search in Google Scholar

Jiménez E., Fernández L., Marin M.L, Martin R., Odriozola J.M., Nueno-Palop C., Narbad A., Olivares M., Xaus J., Rodríguez J.M.: Isolation of commensal bacteria from umbilical cord blood of healthy neonates born by cesarean section. Cur. Microbiol. 51, 270–274 (2005)JiménezE.FernándezL.MarinM.LMartinR.OdriozolaJ.M.Nueno-PalopC.NarbadA.OlivaresM.XausJ.RodríguezJ.M.Isolation of commensal bacteria from umbilical cord blood of healthy neonates born by cesarean sectionCur. Microbiol.51270274200510.1007/s00284-005-0020-316187156Search in Google Scholar

Jiménez E., Marin M.L, Martin R., Odriozola J.M., Olivares M., Xaus J., Fernández L., Rodríguez J.M.: Is meconium from healthy newborns actually sterile? Res. Microbiol. 159, 187–193 (2008)JiménezE.MarinM.LMartinR.OdriozolaJ.M.OlivaresM.XausJ.FernándezL.RodríguezJ.M.Is meconium from healthy newborns actually sterile?Res. Microbiol.159187193200810.1016/j.resmic.2007.12.00718281199Search in Google Scholar

Kabeerdoss J., Ferdous S., Balamurugan R., Mechenro J., Vidya R., Santhanam S., Jana A.K., Ramakrishna B.S.: Development of the gut microbiota in southern Indian infants from birth to 6 months: a molecular analysis. J. Nutr. Sci. 2, e18 (2013)KabeerdossJ.FerdousS.BalamuruganR.MechenroJ.VidyaR.SanthanamS.JanaA.K.RamakrishnaB.S.Development of the gut microbiota in southern Indian infants from birth to 6 months: a molecular analysisJ. Nutr. Sci.2e18201310.1017/jns.2013.6415331025191566Search in Google Scholar

Kasprowicz A., Białecka A.: Ocena biocenozy pochwy – stopnie czystości pochwy. Diagnosta Lab. 2, 23–24 (2008)KasprowiczA.BiałeckaA.Ocena biocenozy pochwy – stopnie czystości pochwyDiagnosta Lab.223242008Search in Google Scholar

Kazimierczak W., Wnęk M., Kamiński K.: Częstość zakażeń pochwy ciężarnych hospitalizowanych w klinice perinatologii i ginekologii w Zabrzu. Ginekol. Pol. 75, 932–936 (2004)KazimierczakW.WnękM.KamińskiK.Częstość zakażeń pochwy ciężarnych hospitalizowanych w klinice perinatologii i ginekologii w ZabrzuGinekol. Pol.759329362004Search in Google Scholar

Kierzkowska M., Młynarczyk G. et al.: Ocena mikroflory bakteryjnej szyjki macicy u kobiet w ciąży. Perinatol. Neonatol. Ginekol. 5126–29 (2012)KierzkowskaM.MłynarczykG.Ocena mikroflory bakteryjnej szyjki macicy u kobiet w ciążyPerinatol. Neonatol. Ginekol.5126292012Search in Google Scholar

Kolokotroni O., Middleton N., Gavatha M., Lamnisos D., Priftis K.N., Yiallouros P.K.: Asthma and atopy in children born by caesarean section: effect modification by family history of allergies – a population based cross-sectional study. BMC Pediatr. 12, 179 (2012)KolokotroniO.MiddletonN.GavathaM.LamnisosD.PriftisK.N.YiallourosP.K.Asthma and atopy in children born by caesarean section: effect modification by family history of allergies – a population based cross-sectional studyBMC Pediatr.12179201210.1186/1471-2431-12-179351116723153011Search in Google Scholar

Kozieł M., Włodarczyk K., Wojton D.: Kształtowanie się mikrobioty jelitowej noworodków a konsekwencje zdrowotne (in) Mikrobiologia medyczna i środowiskowa – wybrane zagadnienia, Lublin, 201714–27.KoziełM.WłodarczykK.WojtonD.Kształtowanie się mikrobioty jelitowej noworodków a konsekwencje zdrowotne (in) Mikrobiologia medyczna i środowiskowa – wybrane zagadnieniaLublin20171427Search in Google Scholar

Kim J.H., Yoo S.M., Sohn Y.H., Jin C.H., Yang Y.S., Hwang I.T.: Predominant Lactobacillus species types of vaginal microbiota in pregnant Korean women: quantification of the five Lactobacillus species and two anaerobes. J. Matern. Fetal Neonatal Med. 30, 2329–2333 (2017)KimJ.H.YooS.M.SohnY.H.JinC.H.YangY.S.HwangI.T.Predominant Lactobacillus species types of vaginal microbiota in pregnant Korean women: quantification of the five Lactobacillus species and two anaerobesJ. Matern. Fetal Neonatal Med.3023292333201710.1080/14767058.2016.124779927756178Search in Google Scholar

Kumar P., Magon N.: Hormones in pregnancy. Niger. Med. J. 53, 179–183 (2012)KumarP.MagonN.Hormones in pregnancyNiger. Med. J.53179183201210.4103/0300-1652.107549364023523661874Search in Google Scholar

Madan J.C., Hoen A.G., Lundgren S.N., Shohreh F.F., Cottingham K.L., Morrison H.G., Sogin M. L., Li H., Moore J.H., Karagas M.R.: Effects of Cesarean delivery and formula supplementation on the intestinal microbiome of six-week old infants, JAMA Pediatr. 170, 212–219 (2016)MadanJ.C.HoenA.G.LundgrenS.N.ShohrehF.F.CottinghamK.L.MorrisonH.G.SoginM. L.LiH.MooreJ.H.KaragasM.R.Effects of Cesarean delivery and formula supplementation on the intestinal microbiome of six-week old infantsJAMA Pediatr.170212219201610.1001/jamapediatrics.2015.3732478319426752321Search in Google Scholar

McFall-Ngai M.: Adaptive immunity: care for the community. Nature 445, 153 (2007)McFall-NgaiM.Adaptive immunity: care for the communityNature445153200710.1038/445153a17215830Search in Google Scholar

MacIntyre D.A., Bennett F.B. et al.: The vaginal microbiome during pregnancy and the postpartum period in a European population. Sci. Rep. 5, 8988 (2015)MacIntyreD.A.BennettF.B.The vaginal microbiome during pregnancy and the postpartum period in a European populationSci. Rep.58988201510.1038/srep08988435568425758319Search in Google Scholar

Malinowska M., Tokarz-Deptuła B., Deptuła W.: Mikrobiom człowieka. Post. Mikrobiol. 56133–42 (2016)MalinowskaM.Tokarz-DeptułaB.DeptułaW.Mikrobiom człowiekaPost. Mikrobiol.56133422016Search in Google Scholar

Markiewicz Z., Kwiatkowski Z.A.: Bakterie, antybiotyki, lekooporność. Wydawnictwo Naukowe PWN, Warszawa (2012)MarkiewiczZ.KwiatkowskiZ.A.Bakterie, antybiotyki, lekoopornośćWydawnictwo Naukowe PWNWarszawa2012Search in Google Scholar

Martinez R.C.R., Franceschini S.A., Patta M.C., Quintana S.M., Nunes A.C., Moreira J.L.S., Anukam K.C., Gregor Reid G., De Martinis E.C.P.: Analysis of vaginal Lactobacilli from healthy and infected brazilian women. Appl. Environ. Microbiol. 74, 4539–4542 (2008)MartinezR.C.R.FranceschiniS.A.PattaM.C.QuintanaS.M.NunesA.C.MoreiraJ.L.S.AnukamK.C.Gregor ReidG.De MartinisE.C.P.Analysis of vaginal Lactobacilli from healthy and infected brazilian womenAppl. Environ. Microbiol.7445394542200810.1128/AEM.00284-08249318318502927Search in Google Scholar

Motevaseli E., Shirzad M., Raoofian R., Hasheminasab S., Hatami M., Dianatpour M., Modarressi M.: Differences in vaginal Lactobacilli composition of iranian healthy and bacterial vaginosis infected women: a comparative analysis of their cytotoxic effects with commercial vaginal probiotics. Iran. Red Crescent Med. J. 15, 199–206 (2013)MotevaseliE.ShirzadM.RaoofianR.HasheminasabS.HatamiM.DianatpourM.ModarressiM.Differences in vaginal Lactobacilli composition of iranian healthy and bacterial vaginosis infected women: a comparative analysis of their cytotoxic effects with commercial vaginal probioticsIran. Red Crescent Med. J.15199206201310.5812/ircmj.3533374574723983998Search in Google Scholar

Moyes D.L., Naglik J.R. et al.: Candidalysin is a fungal peptide toxin critical for mucosal infection. Nature 532, 64–68 (2016)MoyesD.L.NaglikJ.R.Candidalysin is a fungal peptide toxin critical for mucosal infectionNature5326468201610.1038/nature17625485123627027296Search in Google Scholar

Mueller N.T., Bakacs E., Combellick J., Grigoryan Z., Domininguez-Bello M.G.: The infant microbiome development: mom matters. Trends Mol. Med. 21, 109–117 (2015)MuellerN.T.BakacsE.CombellickJ.GrigoryanZ.Domininguez-BelloM.G.The infant microbiome development: mom mattersTrends Mol. Med.21109117201510.1016/j.molmed.2014.12.002446466525578246Search in Google Scholar

Niemiec T.: Zakażenia w położnictwie i ginekologii. Via Medica, Gdańsk (2009)NiemiecT.Zakażenia w położnictwie i ginekologiiVia MedicaGdańsk2009Search in Google Scholar

Kumar N., Beauty B., Sai S.S., Kunal P., Saroj R.: Bacterial vaginosis: etiology and modalities of treatment – a brief note. J. Pharm. Bioallied. Sci. 3, 496–503 (2011)KumarN.BeautyB.SaiS.S.KunalP.SarojR.Bacterial vaginosis: etiology and modalities of treatment – a brief noteJ. Pharm. Bioallied. Sci.3496503201110.4103/0975-7406.90102324969622219582Search in Google Scholar

Olszewska J., Jagusztyn-Krynicka E.: HMP (Human Microbiome Project) - mikroflora jelit oraz jej wpływ na fizjologię i zdrowie człowieka. Post. Mikrobiol. 51, 243–256 (2012)OlszewskaJ.Jagusztyn-KrynickaE.HMP (Human Microbiome Project) - mikroflora jelit oraz jej wpływ na fizjologię i zdrowie człowiekaPost. Mikrobiol.512432562012Search in Google Scholar

Pantoja-, Feliciano I.G., Clemente J.C., Costello E.K., Perez M.E., Blaser M.J., Knight R., Dominguez-Bell M.G.: Biphasic assembly of the murine intestinal microbiota during early development. Multidisc. J. Microbial Ecol. 7, 1112–1115 (2013)Pantoja-FelicianoI.G.ClementeJ.C.CostelloE.K.PerezM.E.BlaserM.J.KnightR.Dominguez-BellM.G.Biphasic assembly of the murine intestinal microbiota during early developmentMultidisc. J. Microbial Ecol.7111211152013Search in Google Scholar

Paczkowska I., Wójtowicz A., Malm A.: Wybrane aspekty farmakoterapii kandydoz. Terapia i Lek 8, 539–543 (2010)PaczkowskaI.WójtowiczA.MalmA.Wybrane aspekty farmakoterapii kandydozTerapia i Lek85395432010Search in Google Scholar

Peleg A. Y., Hogan D.A., Mylonakis E.: Medically important bacterial-fungal interactions. Nat. Rev. Microbiol. 8, 340–349 (2010)PelegA. Y.HoganD.A.MylonakisE.Medically important bacterial-fungal interactionsNat. Rev. Microbiol.8340349201010.1038/nrmicro231320348933Search in Google Scholar

Pluznick L.J.: Gut microbes and host physiology: what happens when you host billions of cuests? Front Endocrinol. 5, 91 (2014)PluznickL.J.Gut microbes and host physiology: what happens when you host billions of cuests?Front Endocrinol.591201410.3389/fendo.2014.00091405584824982653Search in Google Scholar

Podgorskiĭ V.S., Liaskovskiĭ T.M., Kovalenko N.K., Oleshchenko L.T.: Study of vaginal and intestinal microflora of women in the prenatal period and its correction in dysbacteriosis. Mikrobiol. Z. 68, 92–104 (2006)PodgorskiĭV.S.LiaskovskiĭT.M.KovalenkoN.K.OleshchenkoL.T.Study of vaginal and intestinal microflora of women in the prenatal period and its correction in dysbacteriosisMikrobiol. Z.68921042006Search in Google Scholar

Ravel J., Forney L.J. et al.: Vaginal microbiome of reproductive-age women. Proc. Natl. Acad. Sci. USA 108, 4680–4687 (2011)RavelJ.ForneyL.J.Vaginal microbiome of reproductive-age womenProc. Natl. Acad. Sci. USA10846804687201110.1073/pnas.1002611107306360320534435Search in Google Scholar

Romero R., Ravel J. et al.: The composition and stability of the vaginal microbiota of normal pregnant women is different from that of nonpregnant women. Microbiome 2, 4 (2014)RomeroR.RavelJ.The composition and stability of the vaginal microbiota of normal pregnant women is different from that of nonpregnant womenMicrobiome24201410.1186/2049-2618-2-4391680624484853Search in Google Scholar

Shaaban O.M., Abbas A.M., Moharram A.M., Farhan M.M., Hassanen I.H.: Does vaginal douching affect the type of cadidal vulvovaginal infection? Med. Mycol. 53, 817–827 (2015)ShaabanO.M.AbbasA.M.MoharramA.M.FarhanM.M.HassanenI.H.Does vaginal douching affect the type of cadidal vulvovaginal infection?Med. Mycol.53817827201510.1093/mmy/myv04226129887Search in Google Scholar

Smith S.B., Ravel J.: The vaginal microbiota, host defence and reproductive physiology. J. Physiol. 595, 451–463 (2017)SmithS.B.RavelJ.The vaginal microbiota, host defence and reproductive physiologyJ. Physiol.595451463201710.1113/JP271694523365327373840Search in Google Scholar

Strus M., Malinowska M.: Zakres antagonistycznego działania bakterii z rodzaju Lactobacillus na czynniki etiologiczne waginozy bakteryjnej. Med. Dosw. Mikrobiol. 51, 47–57 (1999)StrusM.MalinowskaM.Zakres antagonistycznego działania bakterii z rodzaju Lactobacillus na czynniki etiologiczne waginozy bakteryjnejMed. Dosw. Mikrobiol.5147571999Search in Google Scholar

Strus M.: Podstawy stosowania probiotyków dopochwowych w zakażeniach układu moczowo-płciowego. Zakażenia 4, 40–43 (2005)StrusM.Podstawy stosowania probiotyków dopochwowych w zakażeniach układu moczowo-płciowegoZakażenia440432005Search in Google Scholar

Strus M., Kochan P., Chełmicki Z., Chełmicki A., Stefański G., Dechnik K., Jabłońska E., Heczko P.: Wpływ doustnego podawania trzech probiotycznych szczepów Lactobacillus na poprawę odczynu i składu mikroflory pochwy u kobiet w wieku reprodukcyjnym. Gin. Dypl. 3, 53–59 (2008)StrusM.KochanP.ChełmickiZ.ChełmickiA.StefańskiG.DechnikK.JabłońskaE.HeczkoP.Wpływ doustnego podawania trzech probiotycznych szczepów Lactobacillus na poprawę odczynu i składu mikroflory pochwy u kobiet w wieku reprodukcyjnymGin. Dypl.353592008Search in Google Scholar

Wasiela M., Pieczara A., Hanke W., Kalinka J.: Porównanie częstości występowania bacterial vaginosis między I i III trymestrem ciąży Ginekol. Prakt. 9, 111–114 (2001)WasielaM.PieczaraA.HankeW.KalinkaJ.Porównanie częstości występowania bacterial vaginosis między I i III trymestrem ciążyGinekol. Prakt.91111142001Search in Google Scholar

Ward T., Dominguez-Bello M.G., Heisel T., Al-Ghalith G., Knights D., Gale C.A.: Development of the human mycobiome over the first month of life and cross body sites. mSystems 3, e00140–17 (2018)WardT.Dominguez-BelloM.G.HeiselT.Al-GhalithG.KnightsD.GaleC.A.Development of the human mycobiome over the first month of life and cross body sitesmSystems3e0014017201810.1128/mSystems.00140-17584065429546248Search in Google Scholar

Vandenplas Y., De Greef E., Veereman G.: Prebiotics in infant formula. Gut Microbes 5, 681–687 (2014)VandenplasY.De GreefE.VeeremanG.Prebiotics in infant formulaGut Microbes5681687201410.4161/19490976.2014.972237461522725535999Search in Google Scholar

Vásquez A., Jakobsson T., Ahrné S., Forsum U., Molin G.: Vaginal Lactobacillus flora of healthy Swedish women. J. Clin. Microbiol. 40, 2746–2749 (2002)VásquezA.JakobssonT.AhrnéS.ForsumU.MolinG.Vaginal Lactobacillus flora of healthy Swedish womenJ. Clin. Microbiol.4027462749200210.1128/JCM.40.8.2746-2749.200212068812149323Search in Google Scholar

Ventolini G.: Vaginal Lactobacillus: biofilm formation in vivo – clinical implications. Int. J. Womens Health 7, 243–247 (2015)VentoliniG.Vaginal Lactobacillus: biofilm formation in vivo – clinical implicationsInt. J. Womens Health7243247201510.2147/IJWH.S77956433750525733930Search in Google Scholar

Zhanshan (Sam) M., Lianwei L.: Quantifying the human vaginal community state types (CSTs) with the species specificity index. Peer J. DOI 10.77717/peerj.3366 2017Zhanshan (Sam)M.LianweiL.Quantifying the human vaginal community state types (CSTs) with the species specificity indexPeer J.DOI10.77717/peerj.33662017Open DOISearch in Google Scholar

Zhou X., Hansmann M.A., Davis C.C., Suzuki H., Brown C.J., Schutte U., Pierson J.D., Forney L.J.: The vaginal bacterial communities of japanese women resemble those of women in other racial groups. FEMS Immunol. Med. Microbiol. 58, 169–181 (2010)ZhouX.HansmannM.A.DavisC.C.SuzukiH.BrownC.J.SchutteU.PiersonJ.D.ForneyL.J.The vaginal bacterial communities of japanese women resemble those of women in other racial groupsFEMS Immunol. Med. Microbiol.58169181201010.1111/j.1574-695X.2009.00618.x286894719912342Search in Google Scholar

Recommended articles from Trend MD

Plan your remote conference with Sciendo