Chapter 6 : Therapeutic Opportunities in the Vaginal Microbiome

MyBook is a cheap paperback edition of the original book and will be sold at uniform, low price.

Preview this chapter:
Zoom in

Therapeutic Opportunities in the Vaginal Microbiome, Page 1 of 2

| /docserver/preview/fulltext/10.1128/9781555819705/9781555819699_Chap06-1.gif /docserver/preview/fulltext/10.1128/9781555819705/9781555819699_Chap06-2.gif


In order to design and apply a therapeutic, there must be a vaginal disease or disorder in need of treatment or a condition influenced by the vaginal microbiota. There must also be a way for a new therapeutic agent to function through the microbiome. Those conditions include bacterial vaginosis (BV), aerobic vaginitis (AV), urinary tract infection, urethritis, cervicitis, vulvovaginal candidiasis, vulvodynia, endometriosis, and chorioamnitis. In addition, sexually transmitted infections are included, as arguably some may be prevented by vaginal microbes. Cancer is included, not only because of the association with viral infection, but also because microbial dysbiosis has been associated with cancers at other sites.

Citation: Reid G. 2018. Therapeutic Opportunities in the Vaginal Microbiome, p 149-160. In Britton R, Cani P (ed), Bugs as Drugs. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.BAD-0001-2016
Highlighted Text: Show | Hide
Loading full text...

Full text loading...


Image of Figure 1a
Figure 1a

Different mechanisms by which beneficial microbes might influence vaginal health.

Citation: Reid G. 2018. Therapeutic Opportunities in the Vaginal Microbiome, p 149-160. In Britton R, Cani P (ed), Bugs as Drugs. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.BAD-0001-2016
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 1b
Figure 1b

Different mechanisms by which beneficial microbes might influence vaginal health.

Citation: Reid G. 2018. Therapeutic Opportunities in the Vaginal Microbiome, p 149-160. In Britton R, Cani P (ed), Bugs as Drugs. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.BAD-0001-2016
Permissions and Reprints Request Permissions
Download as Powerpoint


1. Burton JP,, Reid G . 2002. Evaluation of the bacterial vaginal flora of 20 postmenopausal women by direct (Nugent score) and molecular (polymerase chain reaction and denaturing gradient gel electrophoresis) techniques. J Infect Dis 186 : 1770 1780.[CrossRef]
2. Heinemann C,, Reid G . 2005. Vaginal microbial diversity among postmenopausal women with and without hormone replacement therapy. Can J Microbiol 51 : 777 781.[CrossRef]
3. Thies FL,, König W,, König B . 2007. Rapid characterization of the normal and disturbed vaginal microbiota by application of 16S rRNA gene terminal RFLP fingerprinting. J Med Microbiol 56 : 755 761.[CrossRef]
4. Brown CJ,, Wong M,, Davis CC,, Kanti A,, Zhou X,, Forney LJ . 2007. Preliminary characterization of the normal microbiota of the human vulva using cultivation-independent methods. J Med Microbiol 56 : 271 276.[CrossRef]
5. Schellenberg J,, Links MG,, Hill JE,, Dumonceaux TJ,, Peters GA,, Tyler S,, Ball TB,, Severini A,, Plummer FA . 2009. Pyrosequencing of the chaperonin-60 universal target as a tool for determining microbial community composition. Appl Environ Microbiol 75 : 2889 2898.[CrossRef]
6. Kim TK,, Thomas SM,, Ho M,, Sharma S,, Reich CI,, Frank JA,, Yeater KM,, Biggs DR,, Nakamura N,, Stumpf R,, Leigh SR,, Tapping RI,, Blanke SR,, Slauch JM,, Gaskins HR,, Weisbaum JS,, Olsen GJ,, Hoyer LL,, Wilson BA . 2009. Heterogeneity of vaginal microbial communities within individuals. J Clin Microbiol 47 : 1181 1189.[CrossRef]
7. Hummelen R,, Fernandes AD,, Macklaim JM,, Dickson RJ,, Changalucha J,, Gloor GB,, Reid G . 2010. Deep sequencing of the vaginal microbiota of women with HIV. PLoS One 5 : e12078.[CrossRef] [PubMed]
8. Ravel J,, Gajer P,, Abdo Z,, Schneider GM,, Koenig SS,, McCulle SL,, Karlebach S,, Gorle R,, Russell J,, Tacket CO,, Brotman RM,, Davis CC,, Ault K,, Peralta L,, Forney LJ . 2011. Vaginal microbiome of reproductive-age women. Proc Natl Acad Sci USA 108( Suppl 1) : 4680 4687.[CrossRef]
9. Gajer P,, Brotman RM,, Bai G,, Sakamoto J,, Schütte UM,, Zhong X,, Koenig SS,, Fu L,, Ma ZS,, Zhou X,, Abdo Z,, Forney LJ,, Ravel J . 2012. Temporal dynamics of the human vaginal microbiota. Sci Transl Med 4 : 132ra52.[CrossRef]
10. Wylie KM,, Mihindukulasuriya KA,, Zhou Y,, Sodergren E,, Storch GA,, Weinstock GM . 2014. Metagenomic analysis of double-stranded DNA viruses in healthy adults. BMC Biol 12 : 71.[CrossRef] [PubMed]
11. DiGiulio DB,, Callahan BJ,, McMurdie PJ,, Costello EK,, Lyell DJ,, Robaczewska A,, Sun CL,, Goltsman DS,, Wong RJ,, Shaw G,, Stevenson DK,, Holmes SP,, Relman DA . 2015. Temporal and spatial variation of the human microbiota during pregnancy. Proc Natl Acad Sci USA 112 : 11060 11065.[CrossRef]
12. Tamames J,, Abellán JJ,, Pignatelli M,, Camacho A,, Moya A . 2010. Environmental distribution of prokaryotic taxa. BMC Microbiol 10 : 85.[CrossRef] [PubMed]
13. Dridi B,, Raoult D,, Drancourt M . 2011. Archaea as emerging organisms in complex human microbiomes. Anaerobe 17 : 56 63.[CrossRef]
14. Hirt RP,, Sherrard J . 2015. Trichomonas vaginalis origins, molecular pathobiology and clinical considerations. Curr Opin Infect Dis 28 : 72 79.[CrossRef]
15. Borgdorff H,, Verwijs MC,, Wit FW,, Tsivtsivadze E,, Ndayisaba GF,, Verhelst R,, Schuren FH,, van de Wijgert JH . 2015. The impact of hormonal contraception and pregnancy on sexually transmitted infections and on cervicovaginal microbiota in African sex workers. Sex Transm Dis 42 : 143 152.[CrossRef]
16. Ling Z,, Liu X,, Chen X,, Zhu H,, Nelson KE,, Xia Y,, Li L,, Xiang C . 2011. Diversity of cervicovaginal microbiota associated with female lower genital tract infections. Microb Ecol 61 : 704 714.[CrossRef] [PubMed]
17. Zheng NN,, Guo XC,, Lv W,, Chen XX,, Feng GF . 2013. Characterization of the vaginal fungal flora in pregnant diabetic women by 18S rRNA sequencing. Eur J Clin Microbiol Infect Dis 32 : 1031 1040.[CrossRef]
18. Mitchell CM,, Haick A,, Nkwopara E,, Garcia R,, Rendi M,, Agnew K,, Fredricks DN,, Eschenbach D . 2015. Colonization of the upper genital tract by vaginal bacterial species in nonpregnant women. Am J Obstet Gynecol 212 : 611e1 611e9.[CrossRef]
19. Muzny CA,, Sunesara IR,, Kumar R,, Mena LA,, Griswold ME,, Martin DH,, Lefkowitz EJ,, Schwebke JR,, Swiatlo E . 2013. Characterization of the vaginal microbiota among sexual risk behavior groups of women with bacterial vaginosis. PLoS One 8 : e80254.[CrossRef]
20. Di Bella JM,, Bao Y,, Gloor GB,, Burton JP,, Reid G . 2013. High throughput sequencing methods and analysis for microbiome research. J Microbiol Methods 95 : 401 414.[CrossRef]
21. Fernandes AD,, Reid JN,, Macklaim JM,, McMurrough TA,, Edgell DR,, Gloor GB . 2014. Unifying the analysis of high-throughput sequencing datasets: characterizing RNA-seq, 16S rRNA gene sequencing and selective growth experiments by compositional data analysis. Microbiome 2 : 15.[CrossRef]
22. Brooks JP,, Edwards DJ,, Harwich MD II,, Rivera MC,, Fettweis JM,, Serrano MG,, Reris RA,, Sheth NU,, Huang B,, Girerd P,, Vaginal Microbiome Consortium, Strauss JF III,, Jefferson KK,, Buck GA . 2015. The truth about metagenomics: quantifying and counteracting bias in 16S rRNA studies. BMC Microbiol 15 : 66.[CrossRef]
23. Macklaim JM,, Fernandes AD,, Di Bella JM,, Hammond JA,, Reid G,, Gloor GB . 2013. Comparative meta-RNA-seq of the vaginal microbiota and differential expression by Lactobacillus iners in health and dysbiosis. Microbiome 1 : 12.[CrossRef]
24. McGroarty JA,, Reid G,, Bruce AW . 1994. The influence of nonoxynol-9-containing spermicides on urogenital infection. J Urol 152 : 831 833.[PubMed]
25. Reid G,, Bruce AW,, Cook RL,, Llano M . 1990. Effect on urogenital flora of antibiotic therapy for urinary tract infection. Scand J Infect Dis 22 : 43 47.[CrossRef]
26. Ravel J,, Gajer P,, Fu L,, Mauck CK,, Koenig SS,, Sakamoto J,, Motsinger-Reif AA,, Doncel GF,, Zeichner SL . 2012. Twice-daily application of HIV microbicides alter the vaginal microbiota. MBio 3 : e00370-12.[CrossRef]
27. Brown JM,, Hess KL,, Brown S,, Murphy C,, Waldman AL,, Hezareh M . 2013. Intravaginal practices and risk of bacterial vaginosis and candidiasis infection among a cohort of women in the United States. Obstet Gynecol 121 : 773 780.[CrossRef]
28. Mayer BT,, Srinivasan S,, Fiedler TL,, Marrazzo JM,, Fredricks DN,, Schiffer JT . 2015. Rapid and profound shifts in the vaginal microbiota following antibiotic treatment for bacterial vaginosis. J Infect Dis 212 : 793 802.[CrossRef]
29. de Louvois J,, Hurley R,, Stanley VC . 1975. Microbial flora of the lower genital tract during pregnancy: relationship to morbidity. J Clin Pathol 28 : 731 735.[CrossRef]
30. Bruce AW,, Chadwick P,, Hassan A,, VanCott GF . 1973. Recurrent urethritis in women. Can Med Assoc J 108 : 973 976.[PubMed]
31. Schellenberg JJ,, Dumonceaux TJ,, Hill JE,, Kimani J,, Jaoko W,, Wachihi C,, Mungai JN,, Lane M,, Fowke KR,, Ball TB,, Plummer FA . 2012. Selection, phenotyping and identification of acid and hydrogen peroxide producing bacteria from vaginal samples of Canadian and East African women. PLoS One 7 : e41217.[CrossRef]
32. Velraeds MM,, van der Mei HC,, Reid G,, Busscher HJ . 1997. Inhibition of initial adhesion of uropathogenic Enterococcus faecalis to solid substrata by an adsorbed biosurfactant layer from Lactobacillus acidophilus . Urology 49 : 790 794.[CrossRef]
33. Velraeds MM,, van de Belt-Gritter B,, van der Mei HC,, Reid G,, Busscher HJ . 1998. Interference in initial adhesion of uropathogenic bacteria and yeasts to silicone rubber by a Lactobacillus acidophilus biosurfactant. J Med Microbiol 47 : 1081 1085.[CrossRef]
34. Absolom DR,, Lamberti FV,, Policova Z,, Zingg W,, van Oss CJ,, Neumann AW . 1983. Surface thermodynamics of bacterial adhesion. Appl Environ Microbiol 46 : 90 97.[PubMed]
35. Velraeds MMC,, van der Mei HC,, Reid G,, Busscher HJ . 1996. Physicochemical and biochemical characterization of biosurfactants released from Lactobacillus strains. Colloids Surf B Biointerfaces 8 : 51 61.[CrossRef]
36. Roelants SL,, Ciesielska K,, De Maeseneire SL,, Moens H,, Everaert B,, Verweire S,, Denon Q,, Vanlerberghe B,, Van Bogaert IN,, Van der Meeren P,, Devreese B,, Soetaert W . 2016. Towards the industrialization of new biosurfactants: biotechnological opportunities for the lactone esterase gene from Starmerella bombicola . Biotechnol Bioeng 113 : 550 559.[CrossRef]
37. Reid G,, Younes JA,, Van der Mei HC,, Gloor GB,, Knight R,, Busscher HJ . 2011. Microbiota restoration: natural and supplemented recovery of human microbial communities. Nat Rev Microbiol 9 : 27 38.[CrossRef] [PubMed]
38. Stoyancheva G,, Marzotto M,, Dellaglio F,, Torriani S . 2014. Bacteriocin production and gene sequencing analysis from vaginal Lactobacillus strains. Arch Microbiol 196 : 645 653.[CrossRef]
39. Anukam KC,, Macklaim JM,, Gloor GB,, Reid G,, Boekhorst J,, Renckens B,, van Hijum SA,, Siezen RJ . 2013. Genome sequence of Lactobacillus pentosus KCA1: vaginal isolate from a healthy premenopausal woman. PLoS One 8 : e59239.[CrossRef]
40. Verani JR,, McGee L,, Schrag SJ , Division of Bacterial Diseases, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention (CDC) . 2010. Prevention of perinatal group B streptococcal disease–revised guidelines from CDC, 2010. MMWR Recomm Rep 59( RR-10) : 1 36.[PubMed]
41. Patras KA,, Wescombe PA,, Rösler B,, Hale JD,, Tagg JR,, Doran KS . 2015. Streptococcus salivarius K12 limits group B Streptococcus vaginal colonization. Infect Immun 83 : 3438 3444.[CrossRef]
42. Li J,, Wang W,, Xu SX,, Magarvey NA,, McCormick JK . 2011. Lactobacillus reuteri-produced cyclic dipeptides quench agr-mediated expression of toxic shock syndrome toxin-1 in staphylococci. Proc Natl Acad Sci USA 108 : 3360 3365.[CrossRef]
43. Gutiérrez-Barranquero JA,, Reen FJ,, McCarthy RR,, O’Gara F . 2015. Deciphering the role of coumarin as a novel quorum sensing inhibitor suppressing virulence phenotypes in bacterial pathogens. Appl Microbiol Biotechnol 99 : 3303 3316.[CrossRef]
44. Ojala T,, Kankainen M,, Castro J,, Cerca N,, Edelman S,, Westerlund-Wikström B,, Paulin L,, Holm L,, Auvinen P . 2014. Comparative genomics of Lactobacillus crispatus suggests novel mechanisms for the competitive exclusion of Gardnerella vaginalis . BMC Genomics 15 : 1070.[CrossRef]
45. Kirjavainen PK,, Laine RM,, Carter D,, Hammond J-A,, Reid G . 2008. Expression of anti-microbial defense factors in vaginal mucosa following exposure to Lactobacillus rhamnosus GR-1. Int J Probiotics 3 : 99 106.
46. Orlando A,, Linsalata M,, Notarnicola M,, Tutino V,, Russo F . 2014. Lactobacillus GG restoration of the gliadin induced epithelial barrier disruption: the role of cellular polyamines. BMC Microbiol 14 : 19.[CrossRef]
47. Garcia AF,, Benchimol M,, Alderete JF . 2005. Trichomonas vaginalis polyamine metabolism is linked to host cell adherence and cytotoxicity. Infect Immun 73 : 2602 2610.[CrossRef]
48. Hickey RJ,, Abdo Z,, Zhou X,, Nemeth K,, Hansmann M,, Osborn TW III,, Wang F,, Forney LJ . 2013. Effects of tampons and menses on the composition and diversity of vaginal microbial communities over time. BJOG 120 : 695 704, discussion 704–706.[CrossRef] [PubMed]
49. Mobley HL,, Alteri CJ . 2015. Development of a vaccine against Escherichia coli urinary tract infections. Pathogens 5( 1).pii : E1 [CrossRef]
50. Sabharwal N,, Chhibber S,, Harjai K . 2016. Divalent flagellin immunotherapy provides homologous and heterologous protection in experimental urinary tract infections in mice. Int J Med Microbiol 306 : 29 37.[CrossRef]
51. Harrison C,, Britt H,, Garland S,, Conway L,, Stein A,, Pirotta M,, Fairley C . 2014. Decreased management of genital warts in young women in Australian general practice post introduction of national HPV vaccination program: results from a nationally representative cross-sectional general practice study. PLoS One 9 : e105967.[CrossRef]
52. Lazar E,, Varga R . 2011. Gynevac-a vaccine, containing lactobacillus for therapy and prevention of bacterial vaginosis and related diseases. Akush Ginekol (Sofiia) 50 : 36 42.
53. Demont A,, Hacini-Rachinel F,, Doucet-Ladevèze R,, Ngom-Bru C,, Mercenier A,, Prioult G,, Blanchard C . 2016. Live and heat-treated probiotics differently modulate IL10 mRNA stabilization and microRNA expression. J Allergy Clin Immunol 137 : 1264 7.e1, 10.[CrossRef] [PubMed]
54. Donders GG,, Vereecken A,, Bosmans E,, Dekeersmaecker A,, Salembier G,, Spitz B . 2002. Definition of a type of abnormal vaginal flora that is distinct from bacterial vaginosis: aerobic vaginitis. BJOG 109 : 34 43.[CrossRef]
55. Gajer P,, Brotman RM,, Bai G,, Sakamoto J,, Schütte UM,, Zhong X,, Koenig SS,, Fu L,, Ma ZS,, Zhou X,, Abdo Z,, Forney LJ,, Ravel J . 2012. Temporal dynamics of the human vaginal microbiota. Sci Transl Med 4 : 132ra52.[CrossRef]
56. Yeoman CJ,, Thomas SM,, Miller ME,, Ulanov AV,, Torralba M,, Lucas S,, Gillis M,, Cregger M,, Gomez A,, Ho M,, Leigh SR,, Stumpf R,, Creedon DJ,, Smith MA,, Weisbaum JS,, Nelson KE,, Wilson BA,, White BA . 2013. A multi-omic systems-based approach reveals metabolic markers of bacterial vaginosis and insight into the disease. PLoS One 8 : e56111.[CrossRef]
57. McMillan A,, Rulisa S,, Sumarah M,, Macklaim JM,, Renaud J,, Bisanz JE,, Gloor GB,, Reid G . 2015. A multi-platform metabolomics approach identifies highly specific biomarkers of bacterial diversity in the vagina of pregnant and non-pregnant women. Sci Rep 5 : 14174.[CrossRef]
58. Srinivasan S,, Morgan MT,, Fiedler TL,, Djukovic D,, Hoffman NG,, Raftery D,, Marrazzo JM,, Fredricks DN . 2015. Metabolic signatures of bacterial vaginosis. mBio 6 : e00204 e00215.[CrossRef]
59. Steidler L,, Wells JM,, Raeymaekers A,, Vandekerckhove J,, Fiers W,, Remaut E . 1995. Secretion of biologically active murine interleukin-2 by Lactococcus lactis subsp. lactis . Appl Environ Microbiol 61 : 1627 1629.[PubMed]
60. Steidler L,, Neirynck S,, Huyghebaert N,, Snoeck V,, Vermeire A,, Goddeeris B,, Cox E,, Remon JP,, Remaut E . 2003. Biological containment of genetically modified Lactococcus lactis for intestinal delivery of human interleukin 10. Nat Biotechnol 21 : 785 789.[CrossRef]
61. Vandenbroucke K,, Hans W,, Van Huysse J,, Neirynck S,, Demetter P,, Remaut E,, Rottiers P,, Steidler L . 2004. Active delivery of trefoil factors by genetically modified Lactococcus lactis prevents and heals acute colitis in mice. Gastroenterology 127 : 502 513.[CrossRef]
62. Mercenier A,, Müller-Alouf H,, Grangette C . 2000. Lactic acid bacteria as live vaccines. Curr Issues Mol Biol 2 : 17 25.[PubMed]
63. Chang TL,, Chang CH,, Simpson DA,, Xu Q,, Martin PK,, Lagenaur LA,, Schoolnik GK,, Ho DD,, Hillier SL,, Holodniy M,, Lewicki JA,, Lee PP . 2003. Inhibition of HIV infectivity by a natural human isolate of Lactobacillus jensenii engineered to express functional two-domain CD4. Proc Natl Acad Sci USA 100 : 11672 11677.[CrossRef]
64. Marcobal A,, Liu X,, Zhang W,, Dimitrov A,, Jia L,, Lee PP,, Fouts T,, Parks TP,, Lagenaur LA . 2016. Expression of human immunodeficiency virus type 1neutralizing antibody fragments using human vaginal Lactobacillus . AIDS Res Hum Retroviruses 32 : 964 971.[PubMed]
65. Liu JJ,, Reid G,, Jiang Y,, Turner MS,, Tsai CC . 2007. Activity of HIV entry and fusion inhibitors expressed by the human vaginal colonizing probiotic Lactobacillus reuteri RC-14. Cell Microbiol 9 : 120 130.[CrossRef]
66. Barbonetti A,, Vassallo MR,, Cinque B,, Filipponi S,, Mastromarino P,, Cifone MG,, Francavilla S,, Francavilla F . 2013. Soluble products of Escherichia coli induce mitochondrial dysfunction-related sperm membrane lipid peroxidation which is prevented by lactobacilli. PLoS One 8 : e83136.[CrossRef]
67. Weng SL,, Chiu CM,, Lin FM,, Huang WC,, Liang C,, Yang T,, Yang TL,, Liu CY,, Wu WY,, Chang YA,, Chang TH,, Huang HD . 2014. Bacterial communities in semen from men of infertile couples: metagenomic sequencing reveals relationships of seminal microbiota to semen quality. PLoS One 9 : e110152.[CrossRef]
68. Fuentes S,, van Nood E,, Tims S,, Heikamp-de Jong I,, ter Braak CJ,, Keller JJ,, Zoetendal EG,, de Vos WM . 2014. Reset of a critically disturbed microbial ecosystem: faecal transplant in recurrent Clostridium difficile infection. ISME J 8 : 1621 1633.[CrossRef]
69. Anderson GG,, Palermo JJ,, Schilling JD,, Roth R,, Heuser J,, Hultgren SJ . 2003. Intracellular bacterial biofilm-like pods in urinary tract infections. Science 301 : 105 107.[CrossRef]
70. Goneau LW,, Hannan TJ,, MacPhee RA,, Schwartz DJ,, Macklaim JM,, Gloor GB,, Razvi H,, Reid G,, Hultgren SJ,, Burton JP . 2015. Subinhibitory antibiotic therapy alters recurrent urinary tract infection pathogenesis through modulation of bacterial virulence and host immunity. mBio 6 : e00356–e15.[CrossRef]
71. Petrof EO,, Gloor GB,, Vanner SJ,, Weese SJ,, Carter D,, Daigneault MC,, Brown EM,, Schroeter K,, Allen-Vercoe E . 2013. Stool substitute transplant therapy for the eradication of Clostridium difficile infection: ‘RePOOPulating’ the gut. Microbiome 1 : 3.[CrossRef]

This is a required field
Please enter a valid email address
Please check the format of the address you have entered.
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error