Candidate: Dr. Rebecca Brotman is an Assistant Professor with the Institute for Genome Sciences and the Department of Epidemiology and Preventive Medicine at the University of Maryland School of Medicine. This career development award would allow the candidate to expand her training from classical epidemiology to the analysis and translation of metagenomic data. The candidate will be uniquely trained by the end of the award period to integrate microbiome data in molecular epidemiological studies. Background: Vaginal microbiota play an important protective role in maintaining the health of women. Disruption of the mutualistic relationship that exists between bacterial communities in the vagina and their hosts can lead to bacterial vaginosis (BV), a condition in which lactic acid-producing bacteria are supplanted by a diverse array of strictly anaerobic bacteria. Epidemiologically, BV has been shown to be an independent risk factor for adverse outcomes including preterm birth, acquisition of sexually transmitted infections and HIV, and development of pelvic inflammatory disease. National surveys indicate the prevalence of BV among U.S. women is 29%, and yet, despite considerable effort, the cause of BV remains unknown. Moreover, there are no broadly effective therapies for the treatment of BV and recurrence is common. The overarching goal of this project is to better define BV by linking epidemiologic research on risk factors for BV with genomic research on vaginal microbiota to search for the mechanisms that mediate onset and remission. Methods: We will utilize archived vaginal swabs which were collected twice-weekly by 39 women in a 16-week prospective study (1,107 samples). The specimens capture molecular events that take place before, during, and after the spontaneous remission of BV episodes and over the time course of the menstrual cycle. We will apply cultivation-independent methods based on the analysis of 16S rRNA gene sequences amplified from whole genomic DNA isolated from the vaginal swabs. The specimens provide a unique opportunity to investigate four specific aims: 1) Characterize the changes in structure (species composition and rank abundance) of vaginal microbial communities over time;2) Develop a molecular model for the diagnosis of BV;3) Apply model-based statistical approaches to evaluate the relationship between time-varying factors and behaviors with shifts in microbial community composition;and 4) Evaluate the effect of vaginal douching cessation on the vaginal microbiota. Significance: Currently, there is no molecular component to the diagnosis of BV. Use of modern metagenomic technologies in this study will allow us to identify vaginal microbial communities and patterns that are predictive of BV. The proposed studies will facilitate our understanding of vaginal microbiota, drive the development of diagnostic tools for BV and may lead to improved methods for preventing and treating BV. Bacterial vaginosis (BV) is the most common vaginal disease in women, and yet its cause and effective treatment remain unknown. BV is associated with many adverse health outcomes, such as preterm delivery of low birth weight babies and increased risk for infection by HIV. This research will contribute valuable information on the causes of BV, help develop improved methods for diagnosing, preventing and treating BV, and may help reduce major reproductive health problems associated with BV.

Public Health Relevance

Bacterial vaginosis (BV) is the most common vaginal disease in women, and yet its cause and effective treatment remain unknown. BV is associated with many adverse health outcomes, such as preterm delivery of low birth weight babies and increased risk for infection by HIV. This research will contribute valuable information on the causes of BV, help develop improved methods for diagnosing, preventing and treating BV, and may help reduce major reproductive health problems associated with BV.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Scientist Development Award - Research & Training (K01)
Project #
5K01AI080974-05
Application #
8610224
Study Section
Microbiology and Infectious Diseases B Subcommittee (MID)
Program Officer
David, Hagit S
Project Start
2010-03-15
Project End
2015-02-28
Budget Start
2014-03-01
Budget End
2015-02-28
Support Year
5
Fiscal Year
2014
Total Cost
$128,835
Indirect Cost
$9,335
Name
University of Maryland Baltimore
Department
Public Health & Prev Medicine
Type
Schools of Medicine
DUNS #
188435911
City
Baltimore
State
MD
Country
United States
Zip Code
21201
Brotman, Rebecca M; Shardell, Michelle D; Gajer, Pawel et al. (2014) Association between the vaginal microbiota, menopause status, and signs of vulvovaginal atrophy. Menopause 21:450-8
Liu, Su-Hsun; Cummings, Derek A T; Zenilman, Jonathan M et al. (2014) Characterizing the temporal dynamics of human papillomavirus DNA detectability using short-interval sampling. Cancer Epidemiol Biomarkers Prev 23:200-8
Brotman, Rebecca M; Shardell, Michelle D; Gajer, Pawel et al. (2014) Interplay between the temporal dynamics of the vaginal microbiota and human papillomavirus detection. J Infect Dis 210:1723-33
Brotman, Rebecca M; He, Xin; Gajer, Pawel et al. (2014) Association between cigarette smoking and the vaginal microbiota: a pilot study. BMC Infect Dis 14:471
Brotman, Rebecca M; Ravel, Jacques; Bavoil, Patrik M et al. (2014) Microbiome, sex hormones, and immune responses in the reproductive tract: challenges for vaccine development against sexually transmitted infections. Vaccine 32:1543-52
Liu, Su-Hsun; Brotman, Rebecca M; Zenilman, Jonathan M et al. (2013) Menstrual cycle and detectable human papillomavirus in reproductive-age women: a time series study. J Infect Dis 208:1404-15
Shew, Marcia L; Ermel, Aaron C; Weaver, Bree A et al. (2013) Association of Chlamydia trachomatis infection with redetection of human papillomavirus after apparent clearance. J Infect Dis 208:1416-21
Gajer, Pawel; Brotman, Rebecca M; Bai, Guoyun et al. (2012) Temporal dynamics of the human vaginal microbiota. Sci Transl Med 4:132ra52
Brotman, Rebecca M (2011) Vaginal microbiome and sexually transmitted infections: an epidemiologic perspective. J Clin Invest 121:4610-7
Brotman, R M; Melendez, J H; Ghanem, K G (2011) A case control study of anovaginal distance and bacterial vaginosis. Int J STD AIDS 22:231-3

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