Chee et al. Microb Cell Fact (2020) 19:203 https://doi.org/10.1186/s12934-020-01464-4 Microbial Cell Factories REVIEW Open Access Vaginal microbiota and the potential of Lactobacillus derivatives in maintaining vaginal health Wallace Jeng Yang Chee , Shu Yih Chew and Leslie Thian Lung Than* Abstract Human vagina is colonised by a diverse array of microorganisms that make up the normal microbiota and mycobiota. Lactobacillus is the most frequently isolated microorganism from the healthy human vagina, this includes Lactobacil- lus crispatus, Lactobacillus gasseri, Lactobacillus iners, and Lactobacillus jensenii. These vaginal lactobacilli have been touted to prevent invasion of pathogens by keeping their population in check. However, the disruption of vaginal ecosystem contributes to the overgrowth of pathogens which causes complicated vaginal infections such as bacterial vaginosis (BV), sexually transmitted infections (STIs), and vulvovaginal candidiasis (VVC). Predisposing factors such as menses, pregnancy, sexual practice, uncontrolled usage of antibiotics, and vaginal douching can alter the microbial community. Therefore, the composition of vaginal microbiota serves an important role in determining vagina health. Owing to their Generally Recognised as Safe (GRAS) status, lactobacilli have been widely utilised as one of the alterna- tives besides conventional antimicrobial treatment against vaginal pathogens for the prevention of chronic vaginitis and the restoration of vaginal ecosystem. In addition, the efectiveness of Lactobacillus as prophylaxis has also been well-founded in long-term administration. This review aimed to highlight the benefcial efects of lactobacilli deriva- tives (i.e. surface-active molecules) with anti-bioflm, antioxidant, pathogen-inhibition, and immunomodulation activi- ties in developing remedies for vaginal infections. We also discuss the current challenges in the implementation of the use of lactobacilli derivatives in promotion of human health. In the current review, we intend to provide insights for the development of lactobacilli derivatives as a complementary or alternative medicine to conventional probiotic therapy in vaginal health. Keywords: Vaginal microbiota, Vaginal ecosystem, Probiotic, Lactobacillus, Lactobacillus derivatives, Surface-active molecules Background microbes from those anatomical sites [3]. Te fndings Human Microbiome Project (HMP) and Integrative HMP from HMP are deemed signifcant to establish the rela- (iHMP) were funded by the National Institutes of Health tionship between microbiota changes and pathogenesis (NIH). Tey are interdisciplinary efort that engaged in of disease, as well as to identify the biomarkers for diag- human microbiome profling for gut, vaginal, oral, and nostic purpose [4]. skin communities [1, 2]. Both projects aimed to unravel Human vaginal microbiota comprises a diverse array the characteristics, distributions, and metagenomics of of benefcial microbes and opportunistic pathogens that inhabit the vaginal milieu [5, 6]. In order to under- stand the microbiota within human vagina, multiple *Correspondence: [email protected] approaches involving “-omics” technologies have been Department of Medical Microbiology, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400 Serdang, Selangor, Malaysia developed. Molecular approaches that are commonly © The Author(s) 2020. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. 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Collectively, maintaining a harmoni- merase chain reaction-denaturing gradient gel elec- ous balance of vaginal microbiota is crucial for a robust trophoresis (PCR-DGGE), DNA pyrosequencing, host-microbial interaction that promotes healthy vagi- fuorescence insitu hybridisation (FISH), quantitative nal ecosystem. PCR, and microarrays [Reviewed in [7]]. Besides, other Te knowledge advancement in human microbiota has modern “-omics” technologies such as metabolomics, accelerated the pace of new ventures in live biotherapeu- metagenomics, metatranscriptomics, and proteomics tics using benefcial microorganisms [26]. Previously, live have begun to reinvigorate research into the discovery of biotherapeutics via faecal microbiota transplantation functional activity in the microbial communities [8]. Te (FMT) has been proven successful in treating recurrent integration of modern multi’omic data is able to decipher Clostridioides difcile infection [27]. Owing to the suc- the functional insights from complex microbial comuuni- cess of FMT, a similar approach using vaginal microbi- ties through the association of microbial and metabolic ota transplantation (VMT) could be efective in treating profles with the role in mediating human health [8]. To problematic vaginal infections. Recently, the frst VMT date, the vast majority of the human microbiota studies has been reported to be able to reconstitute Lactobacil- utilised 16S rRNA gene sequencing in the identifcation lus-dominated microbiota with no observable adverse of complex microbial communities due to its feasibility in efects in recurrent-BV patients [28]. In addition, patients inferring the representation of certain microbial commu- receiving Lactobacillus co-administered with antibiotics nities that cause diseases [9]. Since the advent of techno- also showed reduced proneness towards recurrent BV logical advances in assessing human microbial diversity, [29]. In a similar study, a combined therapy using met- Ravel et al. [10] have successfully identifed fve distinct ronidazole with both L. rhamnosus GR-1 and L. reuteri bacterial communities by using advanced high-through- RC-14 has successfully treated 88% of BV patients, as put sequencing technology. Te indigenous microbiota in compared to 40% recovery rate for patients receiving only the vaginal milieu is believed to be in a symbiotic rela- metronidazole treatment [30]. It has been suggested that tionship with the host [11]. Fungi, especially Candida these benefcial efects are partly associated with the cell species are likely to exist as commensals in the mucous surface-active molecules (SAMs) such as peptidoglycan layer of vagina and they form part of the complex vagi- (PG), lipoteichoic acid (LTA), biosurfactants (BS) and nal ecosystem with other bacteria [12, 13]. It is suggested exopolysaccharides (EPS) [31, 32]. In fact, Lactobacillus that the fuctuation of microbiota and mycobiota compo- SAMs has been proved to antagonise a plethora of bac- sition in women of reproductive age contributed to the terial and fungal pathogens such as Candida albicans, temporal dynamics in vaginal communities [11]. In fact, Staphylococcus aureus, Streptococcus mutans, Escheri- this fuctuation is infuenced by hormonal changes, age, chia coli, Pseudomonas aeruginosa, and Salmonella typh- sexual practices, and antimicrobial drugs usage [14–17]. imurium [33–35]. Terefore, further understanding in Te microbial dysbiosis in vagina leads to overgrowth of Lactobacillus and its derivatives (i.e. SAMs) could pave opportunistic pathogens and ultimately contributes to way for the development of novel remedy for infections the onset of disease [18]. caused by vaginal dysbiosis. Vaginal dysbiosis refects the disruption of micro- Over the past decade, investigations on vaginal bial community in vagina and is frequently associated microbiota have increased exponentially. Tese stud- with several gynaecological diseases. Multiple studies ies revealed the diversity of microbial communities that have shown the association between vaginal dysbio- shaped up the distinct composition of vagina microfora sis and increased vaginal infections such as bacterial in women [10, 24, 36–38]. Te common fndings from vaginosis (BV), vulvovaginal candidiasis (VVC), sexu- these studies suggested that Lactobacillus-dominated ally transmitted infections (STIs), i.e. trichomoniasis, community is likely to be observed in the healthy-state human papillomavirus (HPV) infection, Chlamydia vagina and higher vaginal pH (less acidic) is reported in trachomatis (CT) infection, human immunodefciency diseased-state vagina. Besides, the microbial composition virus (HIV) susceptibility, and genital herpes infection of vagina in some women are highly dynamic due to sev- [19–23]. One of the most prominent features of vaginal eral predisposing host factors that eventually afects the dysbiosis is the changes in vaginal pH. In a recent study, host-microbial interaction. To date,