Explore This Lab

Overview

Mitchell Lab

The human vaginal bacterial community has important links to reproductive health. The vaginal bacteria most associated with health are Lactobacillus species, which make lactic acid and keep the vaginal pH low. When vaginal Lactobacillus are absent, the many different types of bacteria that are present often lead to a condition known as bacterial vaginosis (BV).

BV is a syndrome, which means it doesn’t have a clear single cause. One focus of the lab is identifying key features of bacteria which may be protective against BV and those which may be linked to the adverse consequences of BV. We perform experiments in the lab to identify the genes and pathways involved in host-microbe interactions. We also enroll participants in cohort studies to collect samples that help us define the impact of different bacteria on people’s symptoms, immunity and health.

Current treatment for BV is antibiotics—either vaginal or oral—and the success of this treatment is limited. Up to 50% of women will have a recurrence of BV after antibiotic treatment. There hasn’t been a fundamentally new treatment or prevention strategy in decades. 

A second focus of the lab is developing new treatments for BV and interventions to promote a health vaginal microbiome.

Our Current Projects

MOTIF (Modifying Organisms Transvaginally in Females)
This is a 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.

Interested in being a healthy donor? LEARN MORE

Interested in being part of the VMT trial? LEARN MORE

KINETICS
This is a study 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 what the best timing for prevention interventions will be, and when people are most vulnerable to re-infection after antibiotic treatment.

VMRC
As part of the Vaginal Microbiome Research Consortium (VMRC), which is funded by the Bill and Melinda Gates Foundation, we are designing a clinical trial to test a novel vaginal live biotherapeutic product to prevent recurrent bacterial vaginosis. The novel treatment 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.

RituxiVag
This is a study of women receiving rituximab, a medication that decreases B-cells in the bloodstream, for treatment of autoimmune disorders. 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.


Lab Members

Learn more about the researchers in our lab.

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

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.

Briah Cooley
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.

Julia Oppenheim

Originally from Chicago, IL, Julia is a rising junior at Tufts University. She is a Psychology major combined with a double minor in Entrepreneurship and Nutrition. She is passionate about learning how different macronutrients and micronutrients affect how our bodies function. She first became interested in women’s health when, at 17, she lost her menstrual cycle for a year. No one could figure out what the root cause was for this change to her body. Her instinct is that her nutrition, or lack thereof, may have played a significant role as to why she lost her menstruation. She believes that proper nutrition starts from having a healthy environment in the womb, which is why vaginal microbiome research is so crucial and something she is proud to be a part of.

Joe Shi, MD
Clinical Research Fellow

Joe grew up around Boston and completed his undergraduate education and medical training in St Louis, MO. He was drawn to women's health due to the patient centered nature of this field as well as the need for better women's health care in many areas of the country and around the world. Joe’s clinical interests involve pelvic floor dysfunction, surgical outcomes, and medical and surgical education. His current research thesis investigates the impact of the vaginal microbiome on epithelial cell healing.

Ashley Tartarilla, MPH
Clinical Research Project Manager

Ashley Tartarilla is a Clinical Research Project Manager in the Mitchell Lab. She has a Master of Arts in Psychology from Boston University and recently completed her Master of Public Health at the University of Massachusetts Amherst, focusing her studies on health equity and public health ethics. Ashley's interest in sexual health began while minoring in gender studies as an undergraduate, and continued during her graduate studies, which included researching the relationship between coping styles and health outcomes among women living with HIV. Ashley is excited to be part of a team dedicated to improving vaginal health for people with chronic bacterial vaginosis. In her free time, Ashley enjoys backpacking in the White Mountains, baking cakes, and spending time with her family in Maine.

In the News

First Vaginal Bacteria Transplants in the US to Begin at Massachusetts General Hospital - WGBH

Publications

Selected 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..

View list of all publications