scholarly journals Quantitative modeling predicts mechanistic links between pre-treatment microbiome composition and metronidazole efficacy in bacterial vaginosis

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Christina Y. Lee ◽  
Ryan K. Cheu ◽  
Melissa M. Lemke ◽  
Andrew T. Gustin ◽  
Michael T. France ◽  
...  
Keyword(s):  
Bacterial Vaginosis ◽  
Critical Factor ◽  
Equation Model ◽  
Gardnerella Vaginalis ◽  
Recurrence Rates ◽  
Associated Bacteria ◽  
Microbiome Composition ◽  
Complex Interactions ◽  
Pre Treatment ◽  
Antibiotic Efficacy

AbstractBacterial vaginosis is a condition associated with adverse reproductive outcomes and characterized by a shift from a Lactobacillus-dominant vaginal microbiota to a polymicrobial microbiota, consistently colonized by strains of Gardnerella vaginalis. Metronidazole is the first-line treatment; however, treatment failure and recurrence rates remain high. To understand complex interactions between Gardnerella vaginalis and Lactobacillus involved in efficacy, here we develop an ordinary differential equation model that predicts bacterial growth as a function of metronidazole uptake, sensitivity, and metabolism. The model shows that a critical factor in efficacy is Lactobacillus sequestration of metronidazole, and efficacy decreases when the relative abundance of Lactobacillus is higher pre-treatment. We validate results in Gardnerella and Lactobacillus co-cultures, and in two clinical cohorts, finding women with recurrence have significantly higher pre-treatment levels of Lactobacillus relative to bacterial vaginosis–associated bacteria. Overall results provide mechanistic insight into how personalized differences in microbial communities influence vaginal antibiotic efficacy.

scholarly journals Novel systems analysis elucidates the influence of personalized variation in microbiome composition on metronidazole efficacy in bacterial vaginosis

2020 ◽  
Author(s):  
Christina Lee ◽  
Ryan Cheu ◽  
Melissa Lemke ◽  
Andrew Gustin ◽  
Michael France ◽  
...  
Keyword(s):  
Bacterial Vaginosis ◽  
Reproductive Tract ◽  
Critical Factor ◽  
Female Reproductive Tract ◽  
Drug Uptake ◽  
Gardnerella Vaginalis ◽  
Lactobacillus Species ◽  
Target Species ◽  
Recurrence Rates ◽  
Pre Treatment

Abstract Bacterial vaginosis (BV) is a syndrome of the female reproductive tract associated with adverse reproductive outcomes and characterized by a shift from a Lactobacillus (LB)-dominant vaginal microbiota to a polymicrobial, anaerobic microbiota, consistently colonized by strains of Gardnerella vaginalis (Gv). The first-line treatment for BV is metronidazole (MNZ); however, treatment failure and recurrence rates remain high. To gain insight into complex interactions between target species (Gv) and non-target Lactobacillus species (Lactobacillus iners (Li)) with MNZ and understand their respective roles in efficacy, we developed an ordinary differential equation model that predicts bacterial growth as a function of drug uptake, metabolism, proliferation, and MNZ sensitivity. Model findings revealed a critical factor in MNZ efficacy may be Li sequestration of MNZ, and that efficacy decreases when the relative abundance of Li is higher pre-treatment. These results were validated in Gv and Li co-cultures (p < 0.001), and in two clinical cohorts, finding women with recurrent BV had significantly lower pre-treatment levels of BV-associated bacteria relative to Lactobacillus spp. (p = 0.0366; p = 0.0484). Overall, model results support a mechanism where non-target Lactobacillus species sequester MNZ from BV-associated target species, such as Gv, promoting BV recurrence by reducing MNZ bioavailability.

scholarly journals NMR metabolomics of symbioses between bacterial vaginosis associated bacteria

2021 ◽  
Author(s):  
Victoria Horrocks ◽  
Charlotte K Hind ◽  
Matthew E Wand ◽  
Joel Chan ◽  
Jade Caitlin Hopkins ◽  
...  
Keyword(s):  
Bacterial Vaginosis ◽  
Gardnerella Vaginalis ◽  
Sequence Variant ◽  
Spontaneous Preterm Birth ◽  
Acetate Production ◽  
Acid Fermentation ◽  
Associated Bacteria ◽  
Symbiotic Relationships ◽  
Mixed Acid ◽  
Metabolic Strategies

Bacterial vaginosis (BV) is a dysbiosis of the vaginal microbiome, characterised by low levels of lactobacilli and overgrowth of a diverse group of bacteria, and associated with higher risk of a variety of infections, surgical complications, cancer and spontaneous preterm birth (PTB). Despite the lack of a consistently applicable aetiology, Prevotella spp. are often associated with both BV and PTB and P. bivia has known symbiotic relationships with both Peptostreptococcus anaerobius and Gardnerella vaginalis. Higher risk of PTB can also be predicted by a composite of metabolites linked to bacterial metabolism but their specific bacterial source remains poorly understood. Here we characterise diversity of metabolic strategies among BV associated bacteria and lactobacilli and the symbiotic metabolic relationships between P. bivia and its partners and show how these influence the availability of metabolites associated with BV/PTB and/or pro- or anti-inflammatory immune responses. We confirm a commensal relationship between Pe. anaerobius and P. bivia, refining its mechanism; P. bivia supplies tyrosine, phenylalanine, methionine, uracil and proline, the last of which leads to a substantial increase in overall acetate production. In contrast, our data indicate the relationship between P. bivia and G. vaginalis strains, with sequence variant G2, is mutualistic with outcome dependent on the metabolic strategy of the G. vaginalis strain. Seven G. vaginalis strains could be separated according to whether they performed mixed acid fermentation (MAF) or bifid shunt (BS). In co-culture, P. bivia supplies all G. vaginalis strains with uracil and received substantial amounts of asparagine in return. Acetate production, which is lower in BS strains, then matched that of MAF strains while production of aspartate increased for the latter. Taken together, our data show how knowledge of inter- and intra-species metabolic diversity and the effects of symbiosis may refine our under-standing of the mechanism and approach to risk prediction in BV and/or PTB.

scholarly journals Two Novel Vaginal Microbicides (Polystyrene Sulfonate and Cellulose Sulfate) Inhibit Gardnerella vaginalis and Anaerobes Commonly Associated with Bacterial Vaginosis

2002 ◽  
Vol 46 (8) ◽  
pp. 2692-2695 ◽  
Author(s):  
Jose A. Simoes ◽  
Diane M. Citron ◽  
Alla Aroutcheva ◽  
Robert A. Anderson ◽  
Calvin J. Chany ◽  
...  
Keyword(s):  
Bacterial Vaginosis ◽  
Gardnerella Vaginalis ◽  
Polystyrene Sulfonate ◽  
Cellulose Sulfate ◽  
Transmitted Infection ◽  
Vaginal Microbicides ◽  
Associated Bacteria ◽  
Sexually Transmitted ◽  
Immunodeficiency Virus

ABSTRACT This is the first report demonstrating the in vitro inhibitory activity of two novel microbicides (cellulose sulfate and polystyrene sulfonate) against bacterial vaginosis (BV)-associated bacteria. Vaginal application of these microbicides not only may reduce the risk of acquisition of human immunodeficiency virus and other sexually transmitted infection-causing organisms but may also decrease the incidence of BV.

scholarly journals Bacterial vaginosis: evaluation of the effectiveness of simultaneous treatment of sexual partners

2020 ◽  
Vol 23 (6) ◽  
pp. 422-431
Author(s):  
V. A. Okhlopkov ◽  
S. V. Barinov ◽  
Yu. I. Tirskaya ◽  
Turan Shakhin kyzy Babaeva ◽  
L. B. Sinelnikova ◽  
...  
Keyword(s):  
Bacterial Vaginosis ◽  
Comparison Group ◽  
Clinical Symptoms ◽  
Sexual Partners ◽  
Main Group ◽  
Reproductive Age ◽  
Gardnerella Vaginalis ◽  
Male Partners ◽  
Associated Bacteria ◽  
Atopobium Vaginae

BACKGROUND: Bacterial vaginosis (BV) is one of the most common diseases affecting women of reproductive age. The main problem of BV is the low efficiency of traditional methods of treatment with a frequent recurrence of up to 50%. MATERIALS AND METHODS: A total of 59 patients were examined and treated with the diagnosis of BV, which was confirmed in accordance with the Amsel criteria. The main group included women with BV and their male partners, whereas the compared group included only women with BV. All women were treated with systemic metronidazole and topical clindamycin, and suppositories with lactic acid were prescribed at the second stage. The men partners were treated systemically with metronidazole and topically with clindamycin. RESULTS: Gardnerella vaginalis, Atopobium vaginae, and Prevotella were the most commonly identified bacteria in the vaginal discharge. In men, BV-associated bacteria were found in the foreskin of the glans penis and distal urethra. The similarity of the microflora of the genital organs of women and their male partners was determined. In women with sexual partners who were treated 6 months after the therapy, the number of BV-associated bacteria was detected two or more times less frequently than in patients in the comparison group. For the men, the number of complaints and clinical symptoms significantly decreased after the treatment. Significant decreases in Gardnerella vaginalis, Atopobium vaginae, Prevotella spp., Leptotrichia amnionii, and Mobiluncus were achieved in the foreskin and Gardnerella in the urethra. In the main group of women, the frequency of BV recurrences recorded was 2.3 times less than that in the comparison group. CONCLUSION: The treatment of partners of women with BV effectively reduces the growth of BV-associated bacteria and significantly decreases the frequency of recurrences.

scholarly journals Human beta defensin levels and vaginal microbiome composition in post-menopausal women diagnosed with lichen sclerosus

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Alexandra Brunner ◽  
Márta Medvecz ◽  
Nóra Makra ◽  
Miklós Sárdy ◽  
Kinga Komka ◽  
...  
Keyword(s):  
Lichen Sclerosus ◽  
Gardnerella Vaginalis ◽  
Control Group ◽  
Vaginal Microbiome ◽  
Microbiome Composition ◽  
Streptococcus Anginosus ◽  
Menopausal Women ◽  
Post Menopausal ◽  
The Individual ◽  
Level Production

AbstractHuman beta defensins (hBDs) may play an important role in the progression of lichen sclerosus (LS), due to their ability to induce excessive stimulation of extracellular matrix synthesis and fibroblast activation. The genetic ability of the individual to produce defensins, the presence of microbes influencing defensin production, and the sensitivity of microbes to defensins together regulate the formation of an ever-changing balance between defensin levels and microbiome composition. We investigated the potential differences in postmenopausal vaginal microbiome composition and vaginal hBD levels in LS patients compared to non-LS controls. LS patients exhibited significantly lower levels of hBD1 (p = 0.0003), and significantly higher levels of hBD2 (p = 0.0359) and hBD3 (p = 0.0002), compared to the control group. The microbiome of the LS patients was dominated by possibly harmful bacteria including Lactobacillus iners, Streptococcus anginosus or Gardnerella vaginalis known to initiate direct or indirect damage by increasing defensin level production. Our observations highlight that correcting the composition of the microbiome may be applicable in supplementary LS therapy by targeting the restoration of the beneficial flora that does not increase hBD2-3 production.

scholarly journals Genome Sequences of 15 Gardnerella vaginalis Strains Isolated from the Vaginas of Women with and without Bacterial Vaginosis: TABLE 1 

2016 ◽  
Vol 4 (5) ◽  
Author(s):  
Lloyd S. Robinson ◽  
Justin Perry ◽  
Sai Lek ◽  
Aye Wollam ◽  
Erica Sodergren ◽  
...  
Keyword(s):  
Preterm Birth ◽  
Health Outcomes ◽  
Bacterial Vaginosis ◽  
Draft Genome ◽  
Gardnerella Vaginalis ◽  
Genome Sequences ◽  
Predominant Species ◽  
Adverse Health ◽  
Adverse Health Outcomes

Gardnerella vaginalis is a predominant species in bacterial vaginosis, a dysbiosis of the vagina that is associated with adverse health outcomes, including preterm birth. Here, we present the draft genome sequences of 15 Gardnerella vaginalis strains (now available through BEI Resources) isolated from women with and without bacterial vaginosis.

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