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Lactobacillus iners , first described in 1999, is a prevalent bacterial species of the vaginal microbiome. As L. iners does not easily grow on de Man-Rogosa-Sharpe agar, but can grow anaerobically on blood agar, it has been initially overlooked by traditional culture methods. It was not until the wide application of molecular biology techniques that the function of L. iners in the vaginal microbiome was carefully explored. L. iners has the smallest genome among known Lactobacilli and it has many probiotic characteristics, but is partly different from other major vaginal Lactobacillus species, such as L. crispatus , in contributing to the maintenance of a healthy vaginal microbiome. It is not only commonly present in the healthy vagina but quite often recovered in high numbers in bacterial vaginosis (BV). Increasing evidence suggests that L. iners is a transitional species that colonizes after the vaginal environment is disturbed and offers overall less protection against vaginal dysbiosis and, subsequently, leads to BV, sexually transmitted infections, and adverse pregnancy outcomes. Accordingly, under certain conditions, L. iners is a genuine vaginal symbiont, but it also seems to be an opportunistic pathogen. Further studies are necessary to identify the exact role of this intriguing species in vaginal health and diseases.

Abstract Background Genital immunology is a key determinant of human immunodeficiency virus (HIV) susceptibility. Both factors are modulated by bacterial vaginosis (BV) and, to some extent, by Lactobacillus iners, the genital Lactobacillus spp. that predominates in African, Caribbean, and other Black (ACB) women. We conducted a clinical trial to assess the impact of oral metronidazole treatment on the genital immune parameters of HIV acquisition risks in Kenyan women with BV. Methods The primary endpoint was ex vivo cervical CD4+ T-cell HIV susceptibility after 1 month; secondary endpoints included genital cytokine/chemokine levels, cervical immune cell populations, and the composition of the cervico-vaginal microbiota by 16S ribosomal RNA gene amplicon sequencing. Results BV resolved (Nugent score ≤ 3) at 1 month in 20/45 participants, and cervical CD4+ T-cell HIV entry was moderately reduced in all participants, regardless of treatment outcome. Resolution of BV and reduced abundances of BV-associated gram-negative taxa correlated with reduced genital interleukin (IL)-1α/β. However, BV resolution and the concomitant colonization by Lactobacillus iners substantially increased several genital chemokines associated with HIV acquisition, including interferon-γ inducible protein (IP)-10, macrophage inflammatory protein (MIP)-3α, and monokine induced by gamma interferon (MIG). In an independent cohort of ACB women, most of whom were BV-free, vaginal chemokines were again closely linked with L. iners abundance, though not other Lactobacillus spp. Conclusions BV treatment reduced genital CD4+ T-cell HIV susceptibility and IL-1 levels, but dramatically increased the genital chemokines that may enhance HIV susceptibility; the latter effect was related to the restoration of an Lactobacillus iners–dominated microbiota. Further studies are needed before treatment of asymptomatic BV can be recommended for HIV prevention in ACB communities. Bacterial vaginosis increases human immunodeficiency virus (HIV) acquisition risks; however, its treatment paradoxically reduces endocervical CD4 T-cell susceptibility to HIV while increasing Lactobacillus iners abundance, causing a broad and dramatic increase in the genital chemokines linked to HIV acquisition risks.

Background The bacterial community present in the female lower genital tract plays an important role in maternal and neonatal health. Imbalances in this microbiota have been associated with negative reproductive outcomes, such as spontaneous preterm birth (sPTB), but the mechanisms underlying the association between a disturbed microbiota and sPTB remain poorly understood. An intrauterine infection ascending from the vagina is thought to be an important contributor to the onset of preterm labour. Our objective was to characterize the vaginal microbiota of pregnant women who had sPTB ( n  = 46) and compare to those of pregnant women who delivered at term ( n  = 170). Vaginal swabs were collected from women at 11–16 weeks of gestational age. Microbiota profiles were created by PCR amplification and pyrosequencing of the cpn 60 universal target region. Results Profiles clustered into seven community state types: I ( Lactobacillus crispatus dominated), II ( Lactobacillus gasseri dominated), III ( Lactobacillus iners dominated), IVA ( Gardnerella vaginalis subgroup B or mix of species), IVC ( G. vaginalis subgroup A dominated), IVD ( G. vaginalis subgroup C dominated) and V ( Lactobacillus jensenii dominated). The microbiota of women who experienced preterm birth (< 37 weeks gestation) had higher richness and diversity and higher Mollicutes prevalence when compared to those of women who delivered at term. The two groups did not cluster according to CST, likely because CST assignment is driven in most cases by the dominance of one particular species, overwhelming the contributions of more rare taxa. In conclusion, we did not identify a specific microbial community structure that predicts sPTB, but differences in microbiota richness, diversity and Mollicutes prevalence were observed between groups. Conclusions Although a causal relationship remains to be determined, our results confirm previous reports of an association between Mollicutes and sPTB and further suggest that a more diverse microbiome may be important in the pathogenesis of some cases.

There has recently been an explosion of studies implicating the human microbiome in playing a critical role in many disease and wellness states. The etiology of abnormal semen analysis (SA) parameters is not identified in 30% of cases; investigations involving the semen microbiome may bridge this gap. Here, we explore the relationship between the semen microbiome and alterations of sperm parameters. We recruited men presenting for fertility evaluation or vasectomy consultation with proven biological paternity. SA and next generation sequencing was performed. Differential abundance testing using Analysis of composition of Microbiota with Bias Correction (ANCOM-BC) was performed along with canonical correlational analysis for microbial community profiling. Men with abnormal (N = 27) sperm motility showed a higher abundance of Lactobacillus iners compared to those with normal (N = 46) sperm motility (mean proportion 9.4% versus 2.6%, p  = 0.046). This relationship persisted on canonical correlational analysis (r = 0.392, p  = 0.011). Men with abnormal sperm concentration (N = 20) showed a higher abundance of Pseudomonas stutzeri (2.1% versus 1.0%, p  = 0.024) and Pseudomonas fluorescens (0.9% versus 0.7%, p  = 0.010), but a lower abundance of Pseudomonas putida (0.5% versus 0.8%, p  = 0.020), compared to those with normal sperm concentration (N = 53). Major limitations are related to study design (cross-sectional, observational). Our results suggest that a small group of microorganisms may play a critical role in observed perturbations of SA parameters. Some of these microbes, most notably Lactobacillus iners , have been described extensively within other, fertility-related, contexts, whereas for others, this is the first report where they have potentially been implicated. Advances in our understanding of the semen microbiome may contribute to potentially new therapeutic avenues for correcting impairments in sperm parameters and improving male fertility.

Cervicovaginal mucus (CVM) can provide a barrier that precludes HIV and other sexually transmitted virions from reaching target cells in the vaginal epithelium, thereby preventing or reducing infections. However, the barrier properties of CVM differ from woman to woman, and the causes of these variations are not yet well understood. Using high-resolution particle tracking of fluorescent HIV-1 pseudoviruses, we found that neither pH nor Nugent scores nor total lactic acid levels correlated significantly with virus trapping in unmodified CVM from diverse donors. Surprisingly, HIV-1 was generally trapped in CVM with relatively high concentrations of d -lactic acid and a Lactobacillus crispatus -dominant microbiota. In contrast, a substantial fraction of HIV-1 virions diffused rapidly through CVM with low concentrations of d -lactic acid that had a Lactobacillus iners -dominant microbiota or significant amounts of Gardnerella vaginalis , a bacterium associated with bacterial vaginosis. Our results demonstrate that the vaginal microbiota, including specific species of Lactobacillus , can alter the diffusional barrier properties of CVM against HIV and likely other sexually transmitted viruses and that these microbiota-associated changes may account in part for the elevated risks of HIV acquisition linked to bacterial vaginosis or intermediate vaginal microbiota. IMPORTANCE Variations in the vaginal microbiota, especially shifts away from Lactobacillus -dominant microbiota, are associated with differential risks of acquiring HIV or other sexually transmitted infections. However, emerging evidence suggests that Lactobacillus iners frequently colonizes women with recurring bacterial vaginosis, raising the possibility that L. iners may not be as protective as other Lactobacillus species. Our study was designed to improve understanding of how the cervicovaginal mucus barrier against HIV may vary between women along with the vaginal microbiota and led to the finding that the vaginal microbiota, including specific species of Lactobacillus , can directly alter the diffusional barrier properties of cervicovaginal mucus. This work advances our understanding of the complex barrier properties of mucus and highlights the differential protective ability of different species of Lactobacillus , with Lactobacillus crispatus and possibly other species playing a key role in protection against HIV and other sexually transmitted infections. These findings could lead to the development of novel strategies to protect women against HIV. Variations in the vaginal microbiota, especially shifts away from Lactobacillus -dominant microbiota, are associated with differential risks of acquiring HIV or other sexually transmitted infections. However, emerging evidence suggests that Lactobacillus iners frequently colonizes women with recurring bacterial vaginosis, raising the possibility that L. iners may not be as protective as other Lactobacillus species. Our study was designed to improve understanding of how the cervicovaginal mucus barrier against HIV may vary between women along with the vaginal microbiota and led to the finding that the vaginal microbiota, including specific species of Lactobacillus , can directly alter the diffusional barrier properties of cervicovaginal mucus. This work advances our understanding of the complex barrier properties of mucus and highlights the differential protective ability of different species of Lactobacillus , with Lactobacillus crispatus and possibly other species playing a key role in protection against HIV and other sexually transmitted infections. These findings could lead to the development of novel strategies to protect women against HIV.

Vaginal microbiota composition affects many facets of reproductive health. Lactobacillus iners -dominated microbial communities are associated with poorer outcomes, including higher risk of bacterial vaginosis (BV), compared with vaginal microbiota rich in L. crispatus . Unfortunately, standard-of-care metronidazole therapy for BV typically results in dominance of L. iners , probably contributing to post-treatment relapse. Here we generate an L. iners isolate collection comprising 34 previously unreported isolates from 14 South African women with and without BV and 4 previously unreported isolates from 3 US women. We also report an associated genome catalogue comprising 1,218 vaginal Lactobacillus isolate genomes and metagenome-assembled genomes from >300 women across 4 continents. We show that, unlike L. crispatus , L. iners growth is dependent on l -cysteine in vitro and we trace this phenotype to the absence of canonical cysteine biosynthesis pathways and a restricted repertoire of cysteine-related transport mechanisms. We further show that cysteine concentrations in cervicovaginal lavage samples correlate with Lactobacillus abundance in vivo and that cystine uptake inhibitors selectively inhibit L. iners growth in vitro. Combining an inhibitor with metronidazole promotes L. crispatus dominance of defined BV-like communities in vitro by suppressing L. iners growth. Our findings enable a better understanding of L. iners biology and suggest candidate treatments to modulate the vaginal microbiota to improve reproductive health for women globally. l -cysteine is required for the growth of Lactobacillus iners , a vaginal microbiome species typically associated with adverse outcomes that lacks cysteine biosynthesis pathways and key uptake mechanisms present in other lactobacilli. Cystine uptake inhibitors can be used to suppress L. iners abundance in vitro in favour of L. crispatus , a species associated with favourable outcomes.

The vaginal microbiome, a relatively simple, low diversity ecosystem crucial for female health, is often dominated by Lactobacillus spp. Detailed strain-level data, facilitated by shotgun sequencing, can provide a greater understanding of the mechanisms of colonization and host-microbe interactions. We analysed 354 vaginal metagenomes from pregnant women in Ireland to investigate metagenomic community state types and strain-level variation, focusing on cell surface interfaces. Our analysis revealed multiple subspecies, with Lactobacillus crispatus and Lactobacillus iners being the most dominant. We found genes, including putative mucin-binding genes, distinct to L. crispatus subspecies. Using 337 metagenome-assembled genomes, we observed a higher number of strain-specific genes in L. crispatus related to cell wall biogenesis, carbohydrate and amino acid metabolism, many under positive selection. A cell surface glycan gene cluster was predominantly found in L. crispatus but absent in L. iners and Gardnerella vaginalis . These findings highlight strain-specific factors associated with colonisation and host-microbe interactions.

Group B Streptococcus (GBS) asymptomatically colonises the vagina of up to 40% of pregnant women and can transmit to neonates during birth, causing neonatal pneumonia, sepsis, meningitis, and significant mortality. Vaginal GBS colonisation can be attributed to a range of host and bacterial factors, which may include the composition of the vaginal microbial community. There are few studies that have examined the vaginal community composition in relation to GBS colonisation throughout pregnancy. Here, we performed 16S rRNA sequencing (V3-V4) on vaginal swabs from women at 24- and 36-weeks’ gestation, who were GBS culture-negative or GBS culture-positive at either 24 weeks or 36 weeks’ gestation or at both timepoints. Vaginal swabs from 93 women were analysed; 46 women were culture-negative, 11 women GBS culture-positive at 24 weeks only, 21 women GBS culture-positive at 36 weeks only and 15 women GBS culture-positive at both timepoints on Brilliance GBS agar. V3-V4 16S rRNA gene amplicon sequencing demonstrated that in women that were GBS culture-positive at 36 weeks gestation only, G. vaginalis was significantly more abundant at 24-weeks’ gestation despite a lack of significant changes in community richness between the 24- and 36-week samples. The vaginal microbial communities of women persistently colonised with GBS, had a significantly higher abundance of Lactobacillus iners , compared to other groups where L. crispatus, L. gasseri or L. jensenii were dominant. We have characterised the vaginal microbial community composition during pregnancy in relation to GBS colonisation status, in a longitudinal study for the first time. The most interesting finding was that in women that were persistently colonised with GBS throughout pregnancy, there was a significant increase in L. iners and significant reduction in L. crispatus abundance. Given the lack of detail of the role that the vaginal microbial community plays in GBS colonisation in the literature, it is imperative that the relationship between L. iners and GBS in this unique environmental niche is further investigated.

Cervicovaginal dysbiosis is an established co-factor of high-risk human papillomavirus (HPV) persistence and cervical neoplastic development, yet most studies address the bacterial compartment in isolation, leaving fungal communities and bacterial-fungal cross-kingdom interactions underexplored, particularly in Central Asian populations. We performed shotgun metagenomic sequencing (mNGS) of cervicovaginal samples from 311 Kazakhstani women undergoing routine cervical screening. HPV status was determined using combined PCR and mNGS methods, and cervical screening was completed using liquid-based cytology (NILM, ASC-US, LSIL, ASC-H). Bacterial, viral, and fungal taxa were profiled from a single shotgun dataset with Kraken2 pipeline. Bacterial community state types (CSTs) were determined based on dominant bacterial species, functional gene content was annotated against KEGG using eggNOG, and covariate-adjusted associations were estimated using MaAsLin3. Mycobiome β-diversity differed significantly by HPV status ( = 0.003). In particular, positivity was significantly associated with HPV presence and with high-risk α-9 HPV in cytologically normal (NILM) samples (OR = 3.6, [1.6-9.6], ≤ 0.001). Covariate-adjusted analysis was consistent with this positive association (q < 0.05). Concurrently, among CSTs, -dominated CST III and dysbiotic -dominated CST IV showed a 3-fold higher prevalence ( < 0.01). Further analysis demonstrated that, functionally, both of these CSTs had depleted capacity for lactate metabolism (ko00620, < 0.0001) and, in particular, for the genetic capacity for pyruvate-dependent H O generation (half that of the -dominated CST I). These findings support as a metabolically permissive rather than protective and suggest cross-kingdom functional signatures as candidate biomarkers for HPV acquisition and persistence in Central Asia, a region previously absent from the cervicovaginal microbiome literature.

We characterized the composition and structure of the vaginal microbiota in a cohort of 149 women with genital Chlamydia trachomatis infection at baseline who were followed quarterly for 9 months after antibiotic treatment. At time of diagnosis, the vaginal microbiota was dominated by Lactobacillus iners or a diverse array of bacterial vaginosis–associated bacteria including Gardnerella vaginalis. Interestingly, L. iners–dominated communities were most common after azithromycin treatment (1 g monodose), consistent with the observed relative resistance of L. iners to azithromycin. Lactobacillus iners–dominated communities have been associated with increased risk of C. trachomatis infection, suggesting that the impact of antibiotic treatment on the vaginal microbiota could favor reinfections. These results provide support for the dual need to account for the potential perturbing effect(s) of antibiotic treatment on the vaginal microbiota, and to develop strategies to protect and restore optimal vaginal microbiota.