Explore This Lab
The primary goal of research in the Mitchell Lab is to increase our understanding of the role of the vaginal microbiome in reproductive health in order to drive novel interventions to improve women’s health. Our work includes clinical studies, translational analyses and experiments at the bench to identify key pathways in host-microbe interactions, and ways to intervene to promote vaginal health. Humans are the only species with a Lactobacillus-dominant vaginal microbiota, thus all of our work involves human samples or human cell lines.
Our Current Projects
MOTIF (Modifying Organisms Transvaginally in Females)
This is an NIH-funded, randomized trial of vaginal microbiome transplant (VMT) to prevent recurrent bacterial vaginosis. In this study, people with a history of recurrent BV are given antibiotic treatment and then randomized to either transplant of Lactobacillus rich vaginal fluid (which is pre-tested to ensure no infections) or sterile water placebo. This study will help us identify what features of healthy vaginal fluid can transfer protection from BV and will allow development of new preventive therapies. This study is part of a close collaboration between the Mitchell Lab and the Kwon Lab at the Ragon Institute of MGH, MIT and Harvard.
Interested in being a healthy donor? LEARN MORE
Interested in being part of the VMT trial? LEARN MORE
This is a study funded by the Bill and Melinda Gates Foundation to evaluate how antibiotic treatment of BV changes the vaginal bacterial community and if/when vaginal Lactobacillus return after treatment. This will provide insight into the best timing for prevention interventions, and when people are most vulnerable to re-infection after antibiotic treatment.
Interested in being a study participant? LEARN MORE
The Vaginal Microbiome Research Consortium (VMRC), is funded by the Bill and Melinda Gates Foundation to develop a novel live biotherapeutic for prevention of bacterial vaginosis. Dr. Mitchell is the sponsor for the Phase 1 clinical trial of this novel product, which is being developed by scientists from around the U.S. and South Africa, and will be tested both here in Boston and in South Africa.
This is an NIH-funded study of women receiving rituximab (a medication that decreases B-cells in the bloodstream) for treatment of autoimmune disorders. The study arose from clinical observations in patients shared between Dr. Mitchell and Dr. John Niles of the Vasculitis and Glomerulonephritis Center. Our goal is to identify the impact of B-cells on the vaginal microbiome and vaginal immunity. This will help us better understand vaginal immunity overall.
Patients seen in the MGH Gynecology clinic, and in Dr. Mitchell’s vulvovaginitis clinic have the opportunity to contribute to an observational cohort study collecting vaginal samples from a wide range of women to improve our understanding of the basic biology of the human vaginal mucosa and microbiota. Samples from this study have already helped us examine links between symptoms, microbiome and inflammatory markers.
In collaboration with Dr. Moran Yassour of the Hebrew University in Jerusalem, we enrolled a cohort of pregnant people and collected maternal and infant samples to better understand the link between C-section delivery and changes in the infant gut microbiome. Our initial findings challenged existing frameworks by showing that the microbiome changes were also seen in babies born by C-section after labor, suggesting that exposure to maternal vaginal microbiota was not sufficient to prevent the changes due to surgical delivery.
Who We Are
Meet Our Team
Caroline Mitchell, MD, MPH
Director, Vulvovaginal Disorders Program, OB/GYN, Mass General
Associate Professor, Obstetrics, Gynecology & Reproductive Biology
Dr. Mitchell is a faculty member in the Vincent Center for Reproductive Biology at Massachusetts General Hospital in Boston and is the director of the Vulvovaginal Disorders Program at the Mass General main campus. Dr. Mitchell received her undergraduate degree from Harvard college, spent two years in the Peace Corps in Southern Africa, then returned to medical school at Harvard. She did her OB/Gyn residency training at the University of Washington in Seattle, where she also received her MPH degree. She spent seven years on faculty at the UW before returning to Boston and Mass General in 2014. Dr. Mitchell spends the majority of her time in the lab doing translational and basic science research, funded by NIH and foundation grants. Her work focuses on the relationship between the vaginal microbiota, mucosal immune responses and reproductive health.
Ofri Bar, MD
Ofri is a joint PhD student in Caroline Mitchell’s lab and Moran Yassour’s lab (The Hebrew University of Jerusalem in Israel). Ofri is interested in studying the mother-to-child transmission of bacteria and how it affects the establishment of the infant gut microbiome in early life.
Prior to beginning PhD research, Ofri completed an MD degree at The Hebrew University. Ofri’s long-term goal is to continue medical practice and training with clinical research, and bring them together.
In Ofri’s free time, she enjoys running, yoga, hiking in nature with her family and messy baking with her son.
Agnes Bergerat-Thompson, PhD
Sr. Research Technologist
Agnes joined the Mitchell Lab in August 2016 to investigate the female reproductive tract microbiome. Her work focuses on developing in vitro models to study the host flora-interaction. She is also studying the mucosal immune system of patients with dysbiotic flora using flow cytometry.
Clinical Research Coordinator I
Briah is a Clinical Research Coordinator in the Mitchell Lab and recently graduated from Macalester College in May 2021 with a BA in Biology. She plans to attend medical school and study obstetrics and gynecology. She is extremely interested in prevention of mother-to-child transmission of HIV (PMTCT) and the development of an HIV vaccine. Briah is interested in studying the vaginal microbiome because it is still an understudied area, and is interested in possible vaginal microbiome differences linked to race and ethnicity.
Vi Duong, MD
Clinical Research Fellow
Originally from Northern Virginia, Vi completed her medical and residency training at Georgetown University Medical Center in Washington, D.C. She was initially drawn to women’s health while volunteering as an undergraduate student in a program aimed at increasing access to high-quality prenatal education for WIC-eligible women. She is currently pursuing a three-year fellowship in Female Pelvic Medicine and Reconstructive Surgery. Her clinical interests include pelvic floor disorders, overactive bladder, and surgical outcomes. Her current research thesis investigates the impact of the vaginal microbiome on primary fibroblast cell healing and proliferation
Wafae El-arar is originally from Morocco and has lived in the Boston area for 19 years. She is a Research Technician in the Mitchell Lab and recently graduated from Stonehill College in May 2021 with a BS in Biology. Wafae is interested in women's health especially because it is an area that is overlooked in healthcare. She hopes that her contributions would make an impact for women around the world.
News Coverage and Publications
Bull ME, Mitchell C, Soria J, Styrchak S, Williams-Wietzikoski C, Legard J, McKernan-Mullin J, Kraft K, Onchiri F, Stern J, Holte S, Ryan KJ, Acosta EP, La Rosa A, Coombs RW, Ticona E, Frenkel LM. Monotypic low-level HIV viremias during antiretroviral therapy are associated with disproportionate production of X4 virions and systemic immune activation. AIDS. 2018 Jul 17;32(11):1389-1401. doi: 10.1097/QAD.0000000000001824.PMID:29683841
Anahtar MN, Gootenberg DB, Mitchell CM, Kwon DS. Cervicovaginal Microbiota and Reproductive Health: The Virtue of Simplicity. Cell Host Microbe. 2018 Feb 14;23(2):159-168. doi: 10.1016/j.chom. 2018.01.013. Review.PMID:29447695
Mitchell CM, Reed SD, Diem S, Larson JC, Newton KM, Ensrud KE, LaCroix AZ, Caan B, Guthrie KA. Efficacy of Vaginal Estradiol or Vaginal Moisturizer vs Placebo for Treating Postmenopausal Vulvovaginal Symptoms: A Randomized Clinical Trial. JAMA Intern Med. 2018 May 1;178(5):681-690. doi: 10.1001/jamainternmed.2018.0116. PMID:29554173
Zhao N, Zhan X, Guthrie KA, Mitchell CM, Larson J. Generalized Hotelling's test for paired compositional data with application to human microbiome studies. Genet Epidemiol. 2018 Jul;42(5):459-469. doi: 10.1002/gepi.22127. Epub 2018 May 7.PMID:29737047
Diem SJ, Guthrie KA, Mitchell CM, Reed SD, Larson JC, Ensrud KE, LaCroix AZ. Effects of vaginal estradiol tablets and moisturizer on menopause-specific quality of life and mood in healthy postmenopausal women with vaginal symptoms: a randomized clinical trial. Menopause. 2018 Oct;25(10):1086-1093. doi: 10.1097/GME.0000000000001131. PMID:29738424
Mitchell CM, Reed SD, Guthrie KA. Good Clinical Practice in Diagnosis of Vulvovaginal Symptoms-Reply. JAMA Intern Med. 2018 Aug 1;178(8):1136-1137. doi: 10.1001/jamainternmed.2018.2856. No abstract available. PMID:30083740
Mitchell CM, Reed SD, Guthrie KA. Time to advocate for better science, and better treatments for women. Menopause. 2018 Oct;25(10):1065-1068. doi: 10.1097/GME.0000000000001175. No abstract available. PMID:30085982
Murphy K, Mitchell CM. The interplay of host immunity and environment on risk for bacterial vaginosis and associated reproductive health outcomes. Journal of Infectious Diseases. 2016 Aug 15;214 Suppl 1:S29-35.
Herbst-Kralovetz M, Pyles R, Ratner A, Sycuro L, Mitchell CM. New Systems for Studying Intercellular Interactions in Bacterial Vaginosis. Journal of Infectious Diseases. 2016 Aug 15;214 Suppl 1:S6-S13
Ticona E, Bull M, Soria J, Tapia K, Legard J, Styrchak S, Williams C, Mitchell CM, La Rosa A, Coombs R, Frenkel L. Biomarkers of inflammation in HIV-infected Peruvian men and women before and during suppressive anti-retroviral therapy (ART). 2015 Aug 24;29(13):1617-22
Dingens A, Carlson T, Reed S, Mitchell CM. Bacterial Vaginosis and Adverse Outcomes Among Full-Term Infants: A Cohort Study. BMC Pregnancy Childbirth. 2016 Sep 22;16(1):278
Mitchell CM, Fredricks D, Agnew K, Hitti J. Hydrogen-peroxide producing lactobacilli are associated with lower levels of vaginal IL1β, independent of bacterial vaginosis. Sex Transm Dis. 2015 Jul;42(7):358-63.
Mitchell CM, Haick A, Nkwopara E, Garcia R, Rendi M, Agnew K, Fredricks DN, Eschenbach D. Colonization of the upper genital tract by vaginal bacterial species in non-pregnant women. Am J Obstet Gynecol. 2014 Dec 16. pii: S0002-9378(14)02438-7.
Gordon D, Gardella C, Eschenbach D, Mitchell CM. High Prevalence of Sexual Dysfunction in a Vulvovaginal Specialty Clinic. J Low Genit Tract Dis. 2014 Sep 25.
Mitchell CM, McLemore L, Westerberg K, Astronomo R, Smythe K, Gardella C, Mack M, Magaret A, Patton D, Agnew K, McElrath MJ, Hladik F, Eschenbach D. Long-term effect of depot medroxyprogesterone acetate on vaginal microbiota, epithelial thickness and HIV target cells. J Infect Dis. 2014 Aug 15;210(4):651-5.
Reed SD, Mitchell CM, Joffe H, Cohen L, Shifren JL, Newton KM, Freeman EW, Larson JC, Manson JE, LaCroix AZ, Guthrie KA. Sexual function in women on estradiol or venlafaxine for hot flushes: a randomized controlled trial. Obstet Gynecol. 2014 Aug;124(2 Pt 1):233-41.
Mitchell CM, Marrazzo J. Bacterial vaginosis and the cervicovaginal immune response. Am J Reprod Immunol. June 2014
Mitchell CM, Gottsch M, Liu C, Fredricks D, Nelson D. Associations between vaginal bacteria and levels of vaginal defense in pregnant women. Am J Obstet Gynecol 2013;208:132.e1-7. [Epub 2012 Nov 19]
Mitchell CM, Fredricks D, Winer R, Koutsky L. Effect of sexual debut on the vaginal microbiota in a cohort of young women. Obstet Gynecol 2012;120:1306-13.
Mitchell C, Balkus J, Fredricks D, et al. Interaction between lactobacilli, bacterial vaginosis-associated bacteria and HIV type 1 RNA and DNA genital shedding in U.S. and Kenyan women. AIDS Res Hum Retroviruses 2013;29:13-9. Epub 2012 Nov 5.
Balkus J, Mitchell C, Agnew K, et al. Detection of hydrogen peroxide-producing Lactobacillus species in the vagina: a comparison of culture and quantitative PCR among HIV-1 seropositive women. BMC Infect Dis 2012;12:188.
Mitchell C, Manhart L, Thomas KK, Agnew K, Marrazzo J. Effect of sexual activity on vaginal colonization with hydrogen-peroxide producing lactobacilli and Gardnerella vaginalis. Sex Transm Dis 2011;38:1137-44.
Mitchell C, Manhart L, Thomas K, Fiedler T, Fredricks D, Marrazzo J. Behavioral predictors of colonization with Lactobacillus crispatus or Lactobacillus jensenii after treatment for bacterial Vaginosis: a cohort study. Infect Dis Obstet Gynecol ;38:1137-44..