Hostname: page-component-78c5997874-8bhkd Total loading time: 0 Render date: 2024-11-10T05:22:59.816Z Has data issue: false hasContentIssue false
  • English
  • Français

Vaginal Microbiota Transplantation: The Next Frontier

Published online by Cambridge University Press:  01 January 2021

Kevin DeLong ,
Fareeha Zulfiqar ,
Diane E. Hoffmann ,
Anita J. Tarzian  and
Laura M. Ensign
Get access Rights & Permissions [Opens in a new window]

Abstract

The success of fecal microbiota transplantation (FMT) as a treatment for Clostrioides difficile infection (CDI) has stirred excitement about the potential for microbiota transplantation as a therapy for a wide range of diseases and conditions. In this article, we discuss vaginal microbiota transplantation (VMT) as “the next frontier” in microbiota transplantation and identify the medical, regulatory, and ethical challenges related to this nascent field. We further discuss what we anticipate will be the first context for testing VMT in clinical trials, prevention of the recurrence of a condition referred to as bacterial vaginosis (BV). We also compare clinical aspects of VMT with FMT and comment on how VMT may be similar to or different from FMT in ways that may affect research design and regulatory decisions.

Type
Symposium 1 Articles
Information
Journal of Law, Medicine & Ethics , Volume 47 , Issue 4: Symposium 1 - The Promise and Challenges of Microbiome-based Therapies. Symposium 2 - Regulation on International Direct-to-Participant Genomic Research , Winter 2019 , pp. 555 - 567
Copyright
Copyright © American Society of Law, Medicine and Ethics 2019

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Gajer, P., Brotman, R.M., and Bai, G., et al., “Temporal Dynamics of the Human Vaginal Microbiota,” Science Translational Medicine 4, no. 132 (2012): 132ra52; Ravel, J., Gajer, P., and Abdo, Z., et al., “Vaginal Microbiome of Reproductive-Age Women,” Proceedings of the National Academies of Science U.S.A. 108, supp. 1 (2011): 4680–4687.CrossRefGoogle Scholar
Bilardi, J., Walker, S., and McNair, R., et al., “Women's Management of Recurrent Bacterial Vaginosis and Experiences of Clinical Care: A Qualitative Study,” PLoS One 11, no. 3 (2016): e0151794.CrossRefGoogle Scholar
Amsel, R., Totten, P.A., and Spiegel, C.A., et al., “Nonspecific Vaginitis. Diagnostic Criteria and Microbial and Epidemio-logic Associations,” American Journal of Medicine 74, no. 1 (1983): 14–22.CrossRefGoogle Scholar
McKinnon, L.R., Achilles, S.L., and Bradshaw, C.S., et al., “The Evolving Facets of Bacterial Vaginosis: Implications for HIV Transmission,” AIDS Research and Human Retroviruses 35, no. 3 (2019): 219–228.CrossRefGoogle Scholar
Martin, D.H. and Marrazzo, J.M., “The Vaginal Microbiome: Current Understanding and Future Directions,” Journal of Infectious Diseases 214, Supp. 1 (2016): S36–41.CrossRefGoogle Scholar
Muzny, C.A. and Schwebke, J.R., “Pathogenesis of Bacterial Vaginosis: Discussion of Current Hypotheses,” Journal of Infectious Diseases 214, Supp. 1 (2016): S1–5.CrossRefGoogle Scholar
Murphy, K. and Mitchell, C.M., “The Interplay of Host Immunity, Environment and the Risk of Bacterial Vaginosis and Associated Reproductive Health Outcomes,” Journal of Infectious Diseases 214, Supp. 1 (2016): S29–35.CrossRefGoogle Scholar
Bradshaw, C.S. and Sobel, J.D., “Current Treatment of Bacterial Vaginosis-Limitations and Need for Innovation,” Journal of Infectious Diseases 214, Supp. 1 (2016): S14–20.CrossRefGoogle Scholar
Martin and Marrazzo, supra note 5; Muzny and Schwebke, supra note 6.Google Scholar
Murphy and Mitchell, supra note 7.Google Scholar
Nugent, R.P., Krohn, M.A., and Hillier, S.L., “Reliability of Diagnosing Bacterial Vaginosis Is Improved by a Standardized Method of Gram Stain Interpretation,” Journal of Clinical Microbiology 29, no. 2 (1991): 297–301; Bautista, C.T., Wurapa, E., and Sateren, W.B., et al., “Bacterial Vaginosis: A Synthesis of the Literature on Etiology, Prevalence, Risk Factors, and Relationship with Chlamydia and Gonorrhea Infections,” Military Medical Research 3 (2016): art. no. 4. doi: 10.1186/s40779-016-0074-5; Kenyon, C., Colebunders, R., and Crucitti, T., “The Global Epidemiology of Bacterial Vaginosis: A Systematic Review,” American Journal of Obstetrics and Gynecology 209, no. 6 (2013): 505–523.CrossRefGoogle Scholar
Koumans, E.H., Sternber, M., and McQuillan, G., et al., “The Prevalence of Bacterial Vaginosis in the United States, 2001-2004; Associations with Symptoms, Sexual Behaviors, and Reproductive Health,” Sexually Transmitted Diseases 34, no. 11 (2007): 864–69.CrossRefGoogle Scholar
Bonham, V.L., Green, E.D., and Perez-Stable, E.J., “Examining How Race, Ethnicity, and Ancestry Data Are Used in Biomedical Research,” Journal of the American Medical Association 320, no. 15 (2018): 1533–1534.CrossRefGoogle Scholar
Murphy and Mitchell, supra note 7.Google Scholar
Id.Google Scholar
Ravel, Gajer, and Abdo, supra note 1.Google Scholar
McKinnon, Achilles, and Bradshaw, et al., supra note 4.Google Scholar
Gajer, Brotman, and Bai, et al., supra note 1; Ravel, J., Brotman, R.M., and Gajer, P., et al., “Daily Temporal Dynamics of Vaginal Microbiota before, during and after Episodes of Bacterial Vaginosis,” Microbiome 1, no. 1 (2013): 29, doi: 10.1186/2049-2618-1-29.CrossRefGoogle Scholar
Ravel, Gajer, and Abdo, et al., supra note 1; Anahtar, M.N., Gootenberg, D.B., Mitchell, C.M., and Kwon, D.S., “Cervicovaginal Microbiota and Reproductive Health: The Virtue of Simplicity,” Cell Host Microbe 23, no. 2 (2018): 159–168; Chen, C., Song, X., and Wei, W., et al., “The Microbiota Continuum along the Female Reproductive Tract and its Relation to Uterine-Related Diseases,” Nature Communications 8, no. 1 (2017): art. no. 875; Smith, S.B. and Ravel, J., “The Vaginal Microbiota, Host Defence and Reproductive Physiology,” Journal of Physiology 595, no. 2 (2017): 451–463.CrossRefGoogle Scholar
Amsel, supra note 3; Nugent supra note 11.Google Scholar
Bilardi, J.E., Walker, S., and Temple-Smith, M., et al., “The Burden of Bacterial Vaginosis: Women's Experience of the Physical, Emotional, Sexual and Social Impact of Living with Recurrent Bacterial Vaginosis,” PLoS One 8, no. 9 (2013): e74378.CrossRefGoogle Scholar
Id.Google Scholar
Allsworth, J.E., Lewis, V.A., and Peipert, J.F., “Viral Sexually Transmitted Infections and Bacterial Vaginosis: 2001–2004 National Health and Nutrition Examination Survey Data,” Sexually Transmitted Diseases 35, no. 9 (2008): 791–796; Brotman, R.M., Klebanoff, M.A., and Nansel, T.R., et al., “Bacterial Vaginosis Assessed by Gram Stain and Diminished Colonization Resistance to Incident Gonococcal, Chlamydial, and Trichomonal Genital Infection,” Journal of Infectious Diseases 202, no. 12 (2010): 1907–1915.Google Scholar
Mastromarino, P., Vitali, B., and Mosca, L., “Bacterial Vaginosis: a Review on Clinical Trials with Probiotics,” New Microbiologica 36, no. 3 (2013): 229–238.Google Scholar
Chen, Song, and Wei, et al., supra note 19.Google Scholar
Reid, G., and Bocking, A., “The Potential for Probiotics to Prevent Bacterial Vaginosis and Preterm Labor,” American Journal of Obstetrics and Gynecology 189, no. 4 (2003): 1202–1208; Taylor, B.D., Darville, T., and Haggerty, C.L., “Does Bacterial Vaginosis Cause Pelvic Inflammatory Disease?” Sexually Transmitted Diseases 40, no. 2 (2013): 117–122.CrossRefGoogle Scholar
Thomas-White, K., Forster, S.C., and Kumar, N., et al., “Culturing of Female Bladder Bacteria Reveals an Interconnected Urogenital Microbiota,” Nature Communications 9, no. 1 (2018): art. no. 1557.CrossRefGoogle Scholar
Stapleton, A.E., “The Vaginal Microbiota and Urinary Tract Infection,” Microbiology Spectrum 4, no. 6 (2016), doi: 10.1128/microbiolspec.UTI-0025-2016; Sumati, A.H. and Saritha, N.K., “Association of Urinary Tract Infection in Women with Bacterial Vaginosis,” Journal of Global Infectious Diseases 1, no. 2 (2009): 151–152.CrossRefGoogle Scholar
Kyrgiou, M., Mitra, A., and Moscicki, A.B., “Does the Vaginal Microbiota Play a Role in the Development of Cervical Cancer?” Translational Research 179 (2017): 168–182; Nené, N.R., Reisel, D., and Leimbach, A., et al., “Association Between the Cervicovaginal Microbiome, BRCA1 Mutation Status, and Risk of Ovarian Cancer: A Case-Control Study,” Lancet Oncology 20, no. 8 (2019): 1171–1182; Xu, W. et al., “Mini-Review: Perspective of the Microbiome in the Pathogenesis of Urothelial Carcinoma,” American Journal of Clinical and Experimental Urology 2, no. 1 (2014): 57–61.CrossRefGoogle Scholar
Bradshaw and Sobel, supra note 8.Google Scholar
Larsson, P.G. and Forsum, U., “Bacterial Vaginosis — a Disturbed Bacterial Flora and Treatment Enigma,” APMIS 113, no. 5 (2005): 305–316; Bradshaw, C.S., Morton, A.N., and Hocking, J., et al., “High Recurrence Rates of Bacterial Vaginosis over the Course of 12 Months after Oral Metronidazole Therapy and Factors Associated with Recurrence,” Journal of Infectious Diseases 193, no. 11 (2006): 1478–1486; Sobel, J.D., Schmitt, C., and Meriwether, C., Long-Term Follow-up of Patients with Bacterial Vaginosis Treated with Oral Metronidazole and Topical Clindamycin,” Journal of Infectious Diseases 167, no. 3 (1993): 783–784.CrossRefGoogle Scholar
Boskey, E.R., Moench, T.R., Hees, P.S., and Cone, R.A., “A Self-Sampling Method to Obtain Large Volumes of Undiluted Cervicovaginal Secretions,” Sexually Transmitted Diseases 30, no. 2 (2003): 107–109.CrossRefGoogle Scholar
Gardner, H.L. and Dukes, C.D., “Haemophilus Vaginalis Vaginitis: A Newly Defined Specific Infection Previously Classified Non-Specific Vaginitis,” American Journal of Obstetrics and Gynecology 69, no. 5 (1955): 962–976.CrossRefGoogle Scholar
Id.Google Scholar
Marrazzo, J.M., Koutsky, L.A., and Eschenbach, D.A., et al., “Characterization of Vaginal Flora and Bacterial Vaginosis in Women Who Have Sex with Women,” Journal of Infectious Diseases 185, no. 9 (2002): 1307–1313.CrossRefGoogle Scholar
Marrazzo, J.M., Thomas, K.K., Agnew, K., and Ringwood, K., “Prevalence and Risks for Bacterial Vaginosis in Women Who Have Sex with Women,” Sexually Transmitted Diseases 37, no. 5 (2010): 335–339.Google Scholar
Marrazzo, J.M., Antonio, M., Agnew, K., and Hillier, S.L., “Distribution of Genital Lactobacillus Strains Shared by Female Sex Partners,” Journal of Infectious Diseases 199, no. 5 (2009): 680–683.CrossRefGoogle Scholar
Id.Google Scholar
Vodstrcil, L.A., Walker, S.M., and Hocking, J.S., et al., “Incident Bacterial Vaginosis (BV) in Women Who Have Sex with Women Is Associated with Behaviors that Suggest Sexual Transmission of BV,” Clinical Infectious Diseases 60, no. 7 (2015): 1042–1053.CrossRefGoogle Scholar
Mueller, N.T. et al., “Bacterial Baptism: Scientific, Regulatory Issues Raised by Vaginal Seeding of C-Section-Born Babies,” Journal of Law, Medicine & Ethics 47, no. 4 (2019): 568–578.CrossRefGoogle Scholar
Huh, S.Y., Rifas-Shiman, S.L., and Zera, C.A., et al., “Delivery by Caesarean Section and Risk of Obesity in Preschool Age Children: A Prospective Cohort Study,” Archives of Disease in Childhood 97, no. 7 (2012): 610–616; Pistiner, M., Gold, D.R., and Abdulkerim, H., et al., “Birth by Cesarean Section, Allergic Rhinitis, and Allergic Sensitization among Children with a Parental History of Atopy,” Journal of Allergy and Clinical Immunology 122, no. 2 (2008): 274–279; Sevelsted, A., Stokholm, J., Bønnelykke, K., and Bisgaard, H., “Cesarean Section and Chronic Immune Disorders,” Pediatrics 135, no. 1 (2015): e92–98; Thavagnanam, S., Fleming, J., and Bromley, A., et al., “A Meta-Analysis of the Association between Caesarean Section and Childhood Asthma,” Clinical and Experimental Allergy 38, no. 4 (2008): 629–633. See also Mueller, N. et al., “Bacterial Baptism: Scientific, Medical and Regulatory Issues Raised by Vaginal Seeding of C-section-born babies,” Journal of Law, Medicine & Ethics 47, no. 4 (2019): 568–578.CrossRefGoogle Scholar
Olszak, T., An, D., and Zeissig, S., et al., “Microbial Exposure during Early Life Has Persistent Effects on Natural Killer T Cell Function,” Science 336, no. 6080 (2012): 489–493.CrossRefGoogle Scholar
Dominguez-Bello, M.G., De Jesus-Laboy, K.M., and Shen, N., et al., “Partial Restoration of the Microbiota of Cesarean-Born Infants Via Vaginal Microbial Transfer,” Nature Medicine 22, no. 3 (2016): 250–253. See also Mueller, supra note 40.CrossRefGoogle Scholar
Id.Google Scholar
N. Mueller et al., supra note 40.Google Scholar
Lloyd-Price, J., Abu-Ali, G., and Huttenhower, C., “The Healthy Human Microbiome,” Genome Medicine 8, no. 1 (2016): art. no. 51; Qin, J., Li, R., and Raes, J., et al., “A Human Gut Microbial Gene Catalogue Established by Metagenomic Sequencing,” Nature 464, no. 7285 (2010): 59–65.CrossRefGoogle Scholar
Theriot, C.M. and Young, V.B., “Interactions between the Gastrointestinal Microbiome and Clostridium difficile,” Annual Review of Microbiology 69 (2015): 445–461.CrossRefGoogle Scholar
Oakley, B.B., Fiedler, T.L., Marrazzo, J.M., and Fredricks, D.N., “Diversity of Human Vaginal Bacterial Communities and Associations With Clinically Defined Bacterial Vaginosis,” Applied and Environmental Microbiology 74, no. 15 (2008): 4898–4909.CrossRefGoogle Scholar
Staley, C., Kelly, C.R., and Brandt, L.J., et al., “Complete Micro-biota Engraftment Is Not Essential for Recovery from Recurrent Clostridium difficile Infection Following Fecal Microbiota Transplantation,” mBio 7, no. 6 (2016): e01965–16, DOI: 10.1128/mBio.01965-16.CrossRefGoogle Scholar
Smillie, C.S., Sauk, J., and Gevers, D., et al., “Strain Tracking Reveals the Determinants of Bacterial Engraftment in the Human Gut Following Fecal Microbiota Transplantation,” Cell Host Microbe 23, no. 2 (2018): 229–40 e5.CrossRefGoogle Scholar
Mayer, B.T., Srinavasan, S., and Fiedler, T.L., et al., “Rapid and Profound Shifts in the Vaginal Microbiota Following Antibiotic Treatment for Bacterial Vaginosis,” Journal of Infectious Diseases 212, no. 5 (2015): 793–802; Petrova, M.I., Reid, G., Vaneechoutte, M., and Lebeer, S., “Lactobacillus iners: Friend or Foe?” Trends in Microbiology 25, no. 3 (2017): 182–191.CrossRefGoogle Scholar
Gajer, Brotman, and Bai et al., supra note 1.Google Scholar
Eiseman, B., Silen, W., Bascom, G.S., and Kouvar, A.J., “Fecal Enema as an Adjunct in the Treatment of Pseudomembranous Enterocolitis,” Surgery 44, no. 5 (1958): 854–859.Google Scholar
van Nood, E., Vreize, A., amd Niewdown, M., et al., “Duodenal Infusion of Donor Feces for Recurrent Clostridium difficile,” New England Journal of Medicine 368, no. 5 (2013): 407–415.CrossRefGoogle Scholar
21 U.S. Code §§ 331(k) and 334.Google Scholar
21 U.S. Code § 379a.Google Scholar
United States v. Regenerative Sciences LLC, 741 F.3d 1314 (D.C. Cir. 2014). See also N. Mueller et al., supra note 40.Google Scholar
United States v. Kaplan, 836 F.3d 1199 (9th Cir. 2016). See also N. Mueller et al., supra note 40.Google Scholar
See N. Mueller et al., supra note 40, citing United States v. Geborde, 278 F.3d 926 (9th Cir. 2002) and United States v. Kaplan, 836 F.3d 1199 (9th Cir. 2016).Google Scholar
Reid, G., “Is Bacterial Vaginosis a Disease?” Applied Microbiology and Biotechnology 102, no. 2 (2018): 553–558.CrossRefGoogle Scholar
Hickey, R.J., Zhou, X., and Settles, M.L., et al., “Vaginal Micro-biota of Adolescent Girls prior to the Onset of Menarche Resemble Those of Reproductive-Age Women,” MBio 6, no. 2 (2015): e00097–15, doi: 10.1128/mBio.00097-15.CrossRefGoogle Scholar
Code of Federal Regulations Sections for Cosmetics Labeling (CFR Title 21, Part 701). 2017, available at <https://www.fda.gov/cosmetics/cosmetics-labeling-regulations/code-federal-regulations-sections-cosmetics-labeling-cfr-title-21-part-701> (last visited October 3, 2019).+(last+visited+October+3,+2019).>Google Scholar
Khoruts, A., Hoffman, D., and Palumbo, F., “The Impact of Regulatory Policies on the Future of Fecal Microbiota Transplantation,” Journal of Law, Medicine & Ethics 47, no. 4 (2019): 482–504.CrossRefGoogle Scholar
Sachs, R.E. and Edelstein, C.A., “Ensuring the Safe and Effective FDA Regulation of Fecal Microbiota Transplantation,” Journal of Law and the Biosciences 2, no. 2 (2015): 396–415.CrossRefGoogle Scholar
21 C.F.R. 1271.3. 2018.Google Scholar
21 C.F.R. 1271.3 (f)(2). 2018.Google Scholar
21 C.F.R. 1271.10. 2018.Google Scholar
Id.Google Scholar
21 C.F.R. 1271.85. 2018.Google Scholar
21 C.F.R. 1271.150. 2018.Google Scholar
21 C.F.R. 1271.290. 2018.Google Scholar
21 U.S. Code § 355c. 2018.Google Scholar
DeLong, K., et al., “Conceptual Design of a Universal Donor Screening Approach for Vaginal Microbiota Transplant,” Frontiers in Cellular and Infection Microbiology (2019), available at <https://www.frontiersin.org/articles/10.3389/fcimb.2019.00306/full> (last visited December 6, 2019).CrossRefGoogle Scholar
Haya, J., Garcia, A., and López-Manzanara, C. L, et al., “Importance of Lactic Acid in Maintaining Vaginal Health: A Review of Vaginitis and Vaginosis Etiopathogenic Bases and a Proposal for a New Treatment,” Open Journal of Obstetrics and Gynecology 4 (2014): 787–799.Google Scholar
Muench, D.F., Kuch, D.J., and Wu, H., et al., “Hydrogen Peroxide-Producing Lactobacilli Inhibit Gonococci in Vitro but not during Experimental Genital Tract Infection,” Journal of Infectious Diseases 199, no. 9 (2009): 1369–1378; Pascual, L., Ruiz, F., Giordano, W., and Barberis, I.L., “Vaginal Colonization and Activity of the Probiotic Bacterium Lactobacillus fermentum L23 in a Murine Model of Vaginal Tract Infection,” Journal of Medical Microbiology 59, no. 3 (2010): 360–364; Zarate, G., Santos, V., and Nader-Macias, M.E., “Protective Effect of Vaginal Lactobacillus paracasei CRL 1289 against Urogenital Infection Produced by Staphylococcus aureus in a mouse Animal Model,” Infectious Diseases in Obstetrics and Gynecology (2009): art. no. 48358.CrossRefGoogle Scholar
Yildirim, S., Yeoman, C.J., and Jange, S.C., et al., “Primate Vaginal Microbiomes Exhibit Species Specificity without Universal Lactobacillus Dominance,” The ISME Journal 8 (2014): 2431–2444.CrossRefGoogle Scholar
Spear, G.T., Gilbert, D., and Sikaroodi, M., et al., “Identification of Rhesus Macaque Genital Microbiota by 16S Pyrosequencing Shows Similarities to Human Bacterial Vaginosis: Implications for Use as an Animal Model for HIV Vaginal Infection,” AIDS Research and Human Retroviruses 26, no. 2 (2010): 193–200.CrossRefGoogle Scholar
Ensign, L.M. and Weld, E.D., “Safety and Efficacy of Vaginal Microbiota Transplant (VMT) in Women with Bacterial Vaginosis (BV),” available at <https://clinicaltrials.gov/ct2/show/NCT03769688> (last visited October 3, 2019).+(last+visited+October+3,+2019).>Google Scholar
CDC, “Nearly half a million Americans suffered from Clostridium difficile infections in a single year,” news release, February 25, 2015, available at <https://www.cdc.gov/media/releases/2015/p0225-clostridium-difficile.html> (last visited October 3, 2019).+(last+visited+October+3,+2019).>Google Scholar
DeLong et al., supra note 73.Google Scholar
21 CFR 1271.150. 2018.Google Scholar
Stegmann, B.J. and Carey, J.C., “TORCH Infections. Toxoplasmosis, Other (syphilis, varicella-zoster, parvovirus B19), Rubella, Cytomegalovirus (CMV), and Herpes infections,” Current Women's Health Reports 2, no. 4 (2002): 253–258.Google Scholar
Costello, S.P., Conlon, M.A., and Vuaran, M.S., S.P., et al., “Faecal Microbiota Transplant for Recurrent Clostridium difficile Infection Using Long-Term Frozen Stool is Effective: Clinical Efficacy and Bacterial Viability Data,” Alimentary Pharmacology and Therapeutics 42, no. 8 (2015): 1011–1018.CrossRefGoogle Scholar
Bradshaw and Sobel, supra note 8.Google Scholar
Wilson, J., “Managing Recurrent Bacterial Vaginosis,” Sexually Transmitted Infections 80, no. 1 (2004): 8–11.CrossRefGoogle Scholar
Surawicz, C.M., Brandt, L.J., and Binion, D.G., et al., “Guidelines for Diagnosis, Treatment, and Prevention of Clostridium difficile Infections,” American Journal of Gastroenterology 108, no. 4 (2013): 478–498, at 499.CrossRefGoogle Scholar
Brotman, R.M., Shardell, M.D., and Gajer, P., et al., “Association between the Vaginal Microbiota, Menopause Status, and Signs of Vulvovaginal Atrophy,” Menopause-the Journal of the North American Menopause Society 21, no. 5 (2014): 450–458.CrossRefGoogle Scholar
Brotman, R.M., Shardell, M.D., and Gajer, P., et al., “Interplay between the Temporal Dynamics of the Vaginal Microbiota and Human Papillomavirus Detection,” Journal of Infectious Diseases 210, no. 11 (2014): 1723–1733; Corey, L., Wald, A., and Patel, R., et al., “Once-daily Valacyclovir to Reduce the Risk of Transmission of Genital Herpes,” New England Journal of Medicine 350, no. 1 (2004): 11–20.CrossRefGoogle Scholar
Khoruts, Hoffmann, and Palumbo, supra note 63.Google Scholar
Ngugi, B.M., Hemmerling, A., and Bukusi, E.A., et al., “Effects of Bacterial Vaginosis-Associated Bacteria and Sexual Intercourse on Vaginal Colonization with the Probiotic Lactobacillus crispatus CTV-05,” Sexually Transmitted Diseases 38, no. 11 (2011): 1020–1027.CrossRefGoogle Scholar
Gajer, Brotman, and Bai, et al., supra note 1.Google Scholar
Woodworth, M.H., Neish, E.M., and Miller, N.S., et al., “Laboratory Testing of Donors and Stool Samples for Fecal Microbiota Transplantation for Recurrent Clostridium difficile Infection,” Journal of Clinical Microbiology 55, no. 4 (2017): 1002–1010.CrossRefGoogle Scholar
U.S. Food and Drug Administration, Bacterial Vaginosis: Developing Drugs for Treatment, Guidance for Industry, August 2019, available at <https://www.fda.gov/media/129530/download> (last visited October 3, 2019).+(last+visited+October+3,+2019).>Google Scholar
U.S. Food and Drug Administration, Guidance for Industry and Food and Drug Administration Staff, Collection of Race and Ethnicity Data in Clinical Trials, October 26, 2016, available at <https://www.fda.gov/media/75453/download> (last visited October 3, 2019).+(last+visited+October+3,+2019).>Google Scholar
Heintzman, J. and Marino, M., “Race and Ethnicity Data in Research,” JAMA 321, no. 12 (2019): 1217–1218.CrossRefGoogle Scholar
UNOS, Odds for receiving a kidney transplant now equal for black, white and Hispanic candidates, July 12, 2017, available at <https://unos.org/news/odds-equal-of-kidney-transplant-for-minorities/> (last visited October 3, 2019).+(last+visited+October+3,+2019).>Google Scholar
Id.Google Scholar
Pacheco, C.M., Daley, S.M., and Brown, T., et al., “Moving Forward: Breaking the Cycle of Mistrust Between American Indians and Researchers,” American Journal of Public Health 103, no. 12 (2013): 2152–2159.CrossRefGoogle Scholar
Alcendor, D.J., “Evaluation of Health Disparity in Bacterial Vaginosis and the Implications for HIV-1 Acquisition in African American Women,” American Journal of Reproductive Immunology 76, no. 2 (2016): 99–107.CrossRefGoogle Scholar
Hoffmann, D.E., Fortenberry, J.D., and Ravel, J., “Are Changes to the Common Rule Necessary to Address Evolving Areas of Research? A Case Study Focusing on the Human Microbiome Project,” Journal of Law, Medicine & Ethics 41, no. 2 (2013): 454–469.CrossRefGoogle Scholar
Id.Google Scholar