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Vaginal Microbiota Of Recurrent Bacterial Vaginosis Patients Under Oral Metronidazole Therapy: Prognosis Based On Specific Species Of Gardnerella And Other Bacterial Vaginosis Associated Species In Association With The Vaginal Microbiome
Date of Award
Biochemistry and Molecular Biology
Bacterial Vaginosis (BV) is a state of vaginal dysbiosis in which BV-associated species displace the typically dominant species of Lactobacillus. This urogenital disease elevates the risk for complications such as pre-term birth, STDs and HIV. Currently, there is no consensus on the etiology of BV. Standard of care treatment is oral metronidazole; however, therapy has high rates of recurrence. Our previous qPCR study of recurrent BV patients (3+ episodes/year) found strong associations of Gardnerella_Gsp07, G. swidsinksii, and G. leopoldii with refractory and recurrent responses, and a robust recovery of Lactobacillus in remission patients. However, these findings were not applicable across all patients, suggesting the involvement of other microbial organisms. This current research analyzed a subset of the initial recurrent BV patient samples (n = 41), collected before and after oral metronidazole treatment, by next generation sequencing of the V4 domain of the 16S ribosomal RNA. Our research identified a collection of species with diagnostic or prognostic value. Elevated pre-treatment levels of Gardnerella_Gsp07 strongly predicted a refractory response in most patients; however, there were a portion of patients, with a refractory response that had low levels of Gardnerella_Gsp07. As an alternate source of virulence, our data showed high titers of Mageeibacillus indolicus (BVAB3) and P. timonensis. While combinations of low levels of Gardnerella_Gsp07 or Finegoldia magna with high levels of Megasphaera lornae, from the pre-treatment visit, were prognostic for a long-term remission response, Megasphaera lornae, individually, predicted long-term remission with high accuracy. Post-treatment, high levels of Gardnerella, Aerococcus christensenii, A. vaginae, L. jensenii, and Megasphaera_2 combined with lower levels of Megasphaera lornae were prognostic to those who would recur compared to those that would achieve long-term remission. We have proposed a model that offers testable hypotheses about the causes of these clinical responses. Our results have shown indirect evidence of refractory responses being associated with the resistance and/or tolerance to metronidazole by means of sequestration and inactivation. Future direction will involve whole genome shotgun sequencing on a larger set of patient samples to overcome the limited phylogeny of 16S rRNA gene along with potential in vitro experiments and clinical trials to improve drug therapies targeting BV.
Mollin, Ashomathi Ashok Sudhamathi, "Vaginal Microbiota Of Recurrent Bacterial Vaginosis Patients Under Oral Metronidazole Therapy: Prognosis Based On Specific Species Of Gardnerella And Other Bacterial Vaginosis Associated Species In Association With The Vaginal Microbiome" (2022). Wayne State University Theses. 864.