Caroline Mitchell, MD, MPH

Mitchell Lab: Caroline Mitchell, MD, MPH

The goal of the Mitchell Lab is to understand how vaginal microbes influence reproductive health and disease. We approach this in two ways: basic science experiments in the lab, and translational studies using patient samples.

Overview

We have as many bacterial cells living in and on us as we do human cells in our bodies. New technologies that test for bacterial DNA and allow identification of slight variations between species and strains have allowed a more comprehensive analysis of microbial communities. A world of new possibilities for learning about the causes of disease is now available.

The human vaginal bacterial community is very different from the gastrointestinal community. While a healthy intestinal community has many different types of bacteria, a healthy vaginal community is dominated by a single species: Lactobacillus.

No other primate species has this same pattern. Absence of vaginal Lactobacillus has been associated with preterm birth, miscarriage, increased risk for HIV and infertility.

Learn more about Dr. Mitchell's research: the microbial population in the female reproductive tract.

Group Members

Principal Investigator:

Caroline Mitchell, MD, MPH
Investigator, Vincent Center for Reproductive Biology, Massachusetts General Hospital
Director, Vulvovaginal Disorders Program, Massachusetts General Hospital
Associate Professor of Obstetrics, Gynecology and Reproductive Biology, Harvard Medical School

Clinical Research Fellow

Patricia Hudson, MD

Laboratory Staff

  • Agnes Bergerat, Research Technologist Sr.
  • Alissa Mitchell, Research Technician I
  • Laura Yockey, Student

.

Research Projects

V2 —Understanding Vulvovaginal Disorders

There are over 10 million office visits yearly for vaginal complaints – and in over 30% of those cases a diagnosis cannot be made. Even when a diagnosis is made, treatment is often ineffective or benefit is of short duration. We are collecting samples from healthy women and those with vulvovaginal complaints to allow us to identify novel microbes or immune pathways that might be causing symptoms, and to develop better ways to treat symptoms. This work is funded by grants from the NIH and the American Association of Obstetricians and Gynecologists Foundation.


OriGiN – The Origin of Gut microbiota in Neonates

Where do babies get their intestinal bacteria? Is it from their mother? Their environment? Studies have shown that being born vaginally leads to a different gastrointestinal bacterial community than being born via C-section, but we don’t know why. In collaboration with Dr. Moran Yassour from the Broad Institute, we are enrolling pregnant women and to try and better understand how the vaginal microbiota influence the infant gastrointestinal microbiome.


Reproductive Immune Response to Microbes

In our basic science lab work, we are using in vitro models of vaginal tissue to study how individual species of bacteria interact with the vaginal immune response. Inflammation in the reproductive tract has been linked to higher risk of HIV acquisition, preterm birth, miscarriage and infertility. By understanding the pathways involved in these responses, we hope to develop strategies to intervene and improve reproductive health. This work is funded by the Doris Duke Charitable Foundation and the MGH Claflin Award.


MsFlash – Living a Healthy Menopause

Dr. Mitchell is a collaborator in a Seattle-based menopause research network that is studying how the vaginal microbial community and vaginal immune response might influence the vaginal symptoms experienced by over half of menopausal women. This work is funded by the NIH.

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..

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