Angela Kelly, MA and Michael Stanclift, ND
This is the last installment of a three-part series on bacterial vaginosis (BV). In part one, we discussed a healthy vaginal microbiome, symptoms, and diagnostic criteria. In part two , we highlighted the risk factors that contribute to BV, the health impacts it can cause, and conventional antimicrobial treatments, along with their propensity for resistance.

As we saw in part two , conventional antimicrobials often only temporarily resolve BV, and contribute to antibiotic resistance. For this reason, many patients turn to alternative treatments. In addition, new therapeutics are appearing and some show great promise. It is important to note that treatments such as boric acid, prebiotics, garlic, vaginal microbiome transplantation, Zataria Multiflora cream, vitamin C, antiseptics, and seaweed extracts have limited clinical data to support their use.  However, multiple clinical trials can be found supporting the use of probiotics for the treatment of BV.

Boric acid
Though toxic if taken orally, boric acid administered intravaginally has been used to treat vaginal infections for over 100 years.1 It can lower the rate of BV recurrences when used as a complementary therapy to antimicrobials.2 A recent study shows the potential for boric acid as a standalone treatment for BV.3 Side effects are uncommon (< 10% of cases) but include watery discharge during treatment, vaginal burning sensations, and vaginal erythema.4

Prebiotics
Prebiotics feed beneficial microorganisms. In a randomized double-blind study from 2012, a prebiotic gel containing prebiotics from the glucooligosaccharides (GOS) family was shown to quickly restore the vaginal microbiota.5 Additionally a clinical study from 2017 showed that prebiotic gels may also improve the success of BV treatments.6

Garlic
A 2013 study comparing garlic tablets to oral metronidazole found that garlic tablets were as effective as metronidazole with far fewer reported side effects.7 Side effects of garlic tablets were more tolerable than metronidazole and included heartburn and nausea.7

Vaginal microbiome transplantation
Vaginal microbiome transplantation (VMT) involves seeding a recipient’s vaginal microbiome with the bacteria from a healthy donor. A 2019 study of VMT successfully treated four out of five participants with intractable and recurrent BV.8 In some cases, multiple VMT treatments may be necessary.8

Zataria multiflora cream
Also known as Shirazian thyme, Zataria multiflora is a plant native to Iran, Afghanistan, and Pakistan. The plant’s essential oil contains thymol and carvacrol, which have antibacterial properties.9 A 2008 clinical trial revealed Zataria multiflora vaginal cream to be as effective in treating BV as metronidazole vaginal cream.9 Adverse side effects of treatment included nausea, vaginal dryness, and burning.

Vitamin C
In a 2011 clinical trial it was shown that when administered intravaginally, silicon-coated vitamin C tablets were as effective as metronidazole gel in treating BV and were beneficial in preventing recurrences.10 However, not all participants were able to tolerate treatment due to itching, burning, and pain.10

Antiseptics
In a study of patients with recurrent BV, Octenidine showed high initial cure rates over 87%; however, the development of bacterial resistance to Octenidine was very high with 37.5% of patients showing complete resistance at three treatments/one-year follow-ups.11 At six months the relapse rate of patients included in this study were as high as 66.6%.11

Seaweed extracts
Preclinical research found that ethanol extract of green seaweed (U. Pertusa) possesses robust antimicrobial activity against G. vaginalis, which may have potential as a future treatment for BV.12

Probiotics: Lactobacillus reuteri RC-14 and Lactobaciullus rhamnosus GR-1
Probiotics are “live microorganisms which when administered in adequate amounts confer a health benefit on the host.”13 Currently, probiotics are not recommended as a standalone treatment for BV. However, supplementation with probiotics appears to be beneficial in managing BV, regardless of concurrent antimicrobial treatment.14
Probiotics are a promising complementary therapy to antimicrobials for the treatment of BV.15-20  Studies have shown that when taken orally, lactobacillus probiotics are safe and can improve the vaginal microbiota.16,21 Lactobacillus reuteri RC-14, which was first isolated from a healthy woman’s urogenital tract, can displace G. vaginalis biofilms in vitro.22Studies combining L. reuteri RC-14 and L. rhamnosus GR-1 show success in colonizing and rebalancing the vaginal microflora.16,21,23 Women treated with a combination of metronidazole, L. rhamnosus GR-1, and L. reuteri RC-14 were more than twice as likely to achieve cure than withantimicrobials alone (88% vs. 40%).15 Another study showed using tinidazole for treating BV was improved when combined with L. rhamnosus GR-1 and L. reuteri RC-14.24 In that study, researchers showed an 87.5% cure rate in probiotic group vs. 50% cure rate in the antibiotic/placebo group.24

​A randomized, double-blind, placebo-controlled trial (RCT) in postmenopausal women with L. rhamnosus GR-1 and L. reuteri RC-14 as a standalone preventative therapy resulted in a shift from “indeterminate” to “normal” vaginal microbiota in 60% of the women in the probiotic group vs. 16% of women in the control group.25 Another RCT revealed that L. rhamnosus GR-1 and L. reuteri RC-14 may prevent BV infections in women with HIV.26
So how do these probiotics, which are taken orally, work to help the vaginal microbiome? L. rhamnosus GR-1 and L. reuteri RC-14 can colonize the vagina from the intestinal tract via the perineum.16,27 Lactobacilli weaken biofilms by producing lactic acid, hydrogen peroxide, bacteriocins, and antiadhesive biosurfactants.20 Biosurfactants produced by L. rhamnosus GR-1 and L. reuteri RC-14 work to disrupt the biofilms created by Gardnerella and residing multispecies anaerobes.20 This disruption allows probiotic strains to displace/crowd out pathogenic bacteria.20 L. rhamnosus GR-1 may also positively impact mucosal immunity, allowing the host to defend against pathogenic bacteria through colonization of the gut or vagina or both.16
With the low long-term cure rate of antibiotics in treating BV and the growing threat of antibiotic resistance, the use of probiotics in treating BV should continue to be explored further.

Final thoughts
BV infections can result in devastating physical, reproductive, and emotional health consequences for women and their partners. The high rate of recurrence underlines the need to improve the current standard of care. Finding personalized, effective, long-term solutions to BV requires ingenuity and tenacity. Emerging BV treatments offer clinicians better solutions to help patients stop the revolving door of BV. Liberating women from a cycle of recurring BV is well worth the endeavor.
Citations

1. Zeron Mullins M et al. BASIC study: is intravaginal boric acid non-inferior to metronidazole in symptomatic bacterial vaginosis? Study protocol for a randomized controlled trial. 2015;16(315).
2. Reichman O et al. Boric acid addition to suppressive antimicrobial therapy for recurrent bacterial vaginosis. Sex Transm Dis. 2009;36:732–734.
3. Marrazzo JM et al. Safety and efficacy of a novel vaginal anti-infective, TOL-463, in the treatment of bacterial vaginosis and vulvovaginal candidiasis: a randomized, single-blind, phase 2, controlled trial. Clin Infect Dis. 2019;68(5):803-809.
4. Iavazzo C et al. Boric acid for recurrent vulvovaginal candidiasis: the clinical J Womens Health. 2011;20:1245–1255.
5. Coste I et al. Safety and efficacy of an intravaginal prebiotic gel in the prevention of recurrent bacterial vaginosis: a randomized double-blind study. Obstet Gynecol Int. 2012;2012:147867.
6. Hakimi S et al. The effect of prebiotic vaginal gel with adjuvant oral metronidazole tablets on treatment and recurrence of bacterial vaginosis: a triple-blind randomized controlled study. Arch Gyn Obstet. 2017;297(1):109-116.
7. Mohammadzadeh F et al. Comparing the therapeutic effects of garlic tablet and oral metronidazole on bacterial vaginosis: a randomized controlled clinical trial. Iran Red Crescent Med J. 2014;16(7):e
8. Lev-Sagie et al. Vaginal microbiome transplantation in women with intractable bacterial vaginosis. Nat Med. 2019;25(10):1500-1504.
9. Simbar M et al. A comparative study of the therapeutic effects of the Zataria multiflora vaginal cream and metronidazole vaginal gel on bacterial vaginosis. Phytomedicine. 2008;15(12):1025-1031.
10. Petersen EE et al. Efficacy of vitamin C vaginal tablets in the treatment of bacterial vaginosis: a randomised, double blind, placebo controlled clinical trial. Arzneimittelforschung. 2011;61(4):260-265.
11. Swidsinski A et al. Polymicrobial Gardnerella biofilm resists repeated intravaginal antiseptic treatment in a subset of women with bacterial vaginosis: a preliminary report. Arch Gynecol Obstet. 2015;291(3):605-609.
12. Ha YM et al. Inhibitory effects of seaweed extracts on the growth of the vaginal bacterium Gardnerella vaginalis. J Environ Biol. 2014;35(3):537-542.
13. FAO/WHO. Evaluation of health and nutritional properties of powder milk and live lactic acid bacteria. http://www.fao.org/es/ESN/Probio/probio.htm. Accessed March 10, 2022.
14. Joseph RJ et al. Finding a balance in the vaginal microbiome: how do we treat and prevent the occurrence of bacterial vaginosis?. Antibiotics (Basel). 2021;10(6):719.
15. Anukam K et al. Augmentation of antimicrobial metronidazole therapy of bacterial vaginosis with oral probiotic Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14: randomized, double-blind, placebo-controlled trial. Microbes Infect. 2006;8(6):1450-1454.
16. Reid G et al. Use of Lactobacillus rhamnosus GR-1 and fermentum RC-14 significantly alters vaginal flora: randomized, placebo-controlled trial in 64 healthy women. FEMS Immunol Med Microbiol. 2003;35:131–134.
17. Petricevic L et al. Randomized, double-blind, placebo-controlled study of oral Lactobacilli to improve the vaginal flora of postmenopausal women. Eur J Obstet Gynecol Reprod Biol. 2008;141(1):54-57.
18. Martinez et al. Improved cure of bacterial vaginosis with single dose of tinidazole (2 g), Lactobacillus rhamnosus GR-1, and Lactobacillus reuteri RC-14: a randomized, double-blind, placebo-controlled trial. Can J Microbiol. 55(2):133-138.
19. Hummelen R et al. Deep sequencing of the vaginal microbiota of women with HIV. PLoS One. 2010;58:12078.
20. McMillan et al. Disruption of urogenital biofilms by lactobacilli. Colloids Surf B Biointerfaces. 2011;86(1):58-64.
21. Liu CM et al. Penile microbiota and female partner bacterial vaginosis in Rakai, Uganda. 2015;6:e00589.
22. Saunders S et al. Effect of Lactobacillus challenge on Gardnerella vaginalis biofilms. Colloids Surf B Biointerfaces. 2007;55(2):138-142.
23. Reid G. The scientific basis for probiotic strains of Lactobacillus. Appl Environ Microbiol. 1999;65:3763-766.
24. Martinez et al. Improved cure of bacterial vaginosis with single dose of tinidazole (2 g), Lactobacillus rhamnosus GR-1, and Lactobacillus reuteri RC-14: a randomized, double-blind, placebo-controlled trial. Can J Microbiol. 55(2):133-138.
25. Petricevic L et al. Randomized, double-blind, placebo-controlled study of oral Lactobacilli to improve the vaginal flora of postmenopausal women. Eur J Obstet Gynecol Reprod Biol. 2008;141(1):54-57.
26. Hummelen R et al. Deep sequencing of the vaginal microbiota of women with HIV. PLoS One. 2010;58:12078.
27. Yang S et al. Effect of oral probiotic Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14 on the vaginal microbiota, cytokines and chemokines in pregnant women. Nutrients. 2020;12(2):368.

Angela Kelly, MA and Michael Stanclift, ND
This is part two in a three-part series about bacterial vaginosis (BV). In part one we discussed a healthy vaginal microbiome, BV’s characteristics, and diagnostic criteria. In this section, we’ll explore risk factors for developing BV, the health impacts of it, and current conventional therapies.

BV risk factors
While the precise causes of BV are still being investigated, researchers have discovered the following risk factors that can contribute to its development:

• Having a sexual partner with a history of BV1
• Douching2-3
• Smoking4-5
• Recent antibiotic use5-6
• Being a Black or Mexican-American woman1,3,7-9
• Menstruation2,5,10-11
• Pregnancy5,12
• Having an IUD (especially copper)13
• New sexual partner(s)—result in a 2.5-fold increased risk1,4
• Uncircumcised sexual partner(s)4,14
• Inconsistent condom use4
• Previous STI diagnosis15-16Having female sexual partners or both female and male sexual partners1,4,17
• Becoming sexually active at 14 years of age or younger18
• Socioeconomic status5,19
• Chronic stress20-21
• Obesity22

Health impact of BV
Although most cases of BV are asymptomatic, BV can still have devastating health consequences. Even without symptoms, BV can cause:

• Genital inflammation23
• Increased risk of contracting and passing STIs, including a 60% increase in the acquisition of HIV23-30
• Impaired healing of the epithelial barrier11,31
• Increased risk of HPV infection and resulting cervical cancer11,32
• Infertility33-35
• Increased risk of pelvic inflammatory disease (PID)36-38
• Failure of in vitro fertilization39
• Miscarriage12,39,40
• Amniotic fluid infection41
• Preterm birth42-44,45-46
• Postsurgical infections47

Beyond the raised physical health risks, BV is associated with a significant negative impact on self-esteem, sexual relationships, and quality of life.48 Women report feelings of shame, stress, anxiety over loss of control over recurrent infections, and fear of others’ detection of odor or discharge. With approximately 29% of women in the US suffering from BV, more effective and lasting treatments are needed to reduce the health and economic burden of bacterial vaginosis.22

Current antimicrobial therapeutics and resistance
Current antimicrobial therapeutics often provide only temporary relief and ultimately contribute to antibiotic resistance. BV is usually treated with metronidazole, clindamycin, or a combination of oral and intravaginal antibiotic therapies.49Occasionally other antibiotics such as rifaximin, secnidazole, and tinidazole are prescribed.49-51 A 2020 in vitro study showed clindamycin had greater initial effectiveness against G. vaginalis than metronidazole; however, clindamycin is strongly associated with antibiotic resistance.52-53 In a randomized clinical trial 17% of cases had baseline clindamycin resistance, and 53% showed resistance to it after therapy.53 Also of consideration, clindamycin has been linked to Clostridioides difficile (C. diff) colonization and pseudomembranous colitis.13,50,54 Studies demonstrate G. vaginalis and A. vaginae also show resistance to metronidazole, although to a lesser extent than clindamycin.52,55 When metronidazole is used to treat BV, it can break up the biofilm created by G. vaginalis and A. Vaginae; however, live cells can persist within the biofilm, allowing for recurrences.56 Microbial profiling shows metronidazole temporarily reduces vaginal microbial diversity, and the reestablished microbiota rarely returns to a balanced lactobacilli-dominant state.57 Treatment with metronidazole frequently causes the adverse effects of nausea, vomiting, GI disturbances, and metallic taste.54,58 Occasionally metronidazole may also cause seizures, peripheral neuropathy, transient neutropenia, and allergic reactions, including anaphylaxis.58

These findings highlight that effective and lasting treatments for BV are urgently needed. The pipeline of antibiotics continues to dwindle, and bacteria grow more resistant with the antibiotic treatment of each episode.59 The treatment of protracted or recurring cases of BV often results in a revolving door of relapses for patients.59 Identifying lasting treatments for BV that rely less on antibiotics is of the utmost urgency.60,61

BV recurrence after antimicrobials
The recurrence rate following treatment of BV with antibiotics is high, with a study revealing that 58% of participants experienced a recurrence within a year and 69% returned to abnormal vaginal profiles.50,58  The high rate of recurrence appears to be multifaceted, linked to biofilms created by G. vaginalis and A. vaginae, impaired immune system response, antibiotic resistance, hygiene practices, and, according to some researchers, sexual transmission and reinfection by a woman’s sexual partner(s).60-63 Although there are variations in studies, a recent study showed improved BV recurrence rates when male partners were treated with oral and topical antibiotics. More research on the efficacy of treating sexual partners is needed.64 Having an untreated sexual partner is linked to a raised risk of recurrence of BV, although more research is needed.63,65
We can see the contributing factors for BV are multifactorial and that simple antimicrobial therapies are failing the majority of women they are prescribed to help. In our next and final installment in this series  we’ll explore alternative and emerging treatments for BV, including the role of probiotics. We’ll see how a problem characterized by microbial overgrowth may ultimately need more microbes to see its resolution.
Citations

1. Plummer EL et al. Combined oral and topical antimicrobial therapy for male partners of women with bacterial vaginosis: acceptability, tolerability and impact on the genital microbiota of couples – a pilot study. PLoS One. 2018;13(1):e
2. Borges S et al. The role of lactobacilli and probiotics in maintaining vaginal health. Arch Gynecol Obstet. 2014;289:479-489.
3. Ness S et al. Can known risk factors explain racial differences in the occurrence of bacterial vaginosis? J Natl Med Assoc. 2003;95:201-212.
4. Bradshaw CS et al. High recurrence rates of bacterial vaginosis over the course of 12 months after oral metronidazole therapy and factors associated with recurrence. J Infect Dis. 2006;193:1478–1489.
5. Amabebe E et al. Mechanistic insights into immune suppression and evasion in bacterial vaginosis. Curr microbiol. 2022;79(3):84.
6. Wilks M et al. Identification and H(2)O(2) production of vaginal lactobacilli from pregnant women at high risk of preterm birth and relation with outcome. J Clin Microbiol. 2004;42(2):713-717.
7. Peebles K et al. High global burden and costs of bacterial vaginosis: a systematic review and meta-analysis. Sex Transm Dis. 2019;46(5):304-311.
8. https://www.cdc.gov/std/bv/stats.htm. Accessed September 19, 2022.
9. Hensel KJ et al. Pregnancy-specific association of vitamin D deficiency and bacterial vaginosis. Am J Obstet Gynecol. 2011;204(1):e1-41.e419.
10. Reid G et al. Use of Lactobacillus rhamnosus GR-1 and fermentum RC-14 significantly alters vaginal flora: randomized, placebo-controlled trial in 64 healthy women. FEMS Immunol Med Microbiol. 2003;35:131–134.
11. Coudray MS et al. Bacterial vaginosis-a brief synopsis of the literature. Eur J Obstet Gynecol Reprod Biol. 2020;245:143-148.
12. Nelson DB et al. Bacterial vaginosis in pregnancy: current findings and future directions. Epidemiol Rev. 2002;24(2):102-108.
13. Joseph RJ et al. Finding a balance in the vaginal microbiome: how do we treat and prevent the occurrence of bacterial vaginosis?. Antibiotics (Basel). 2021;10(6):719.
14. Plummer EL et al. Lactic acid-containing products for bacterial vaginosis and their impact on the vaginal microbiota: A systematic review. PloS One. 2021;16(2):e0246953-e0246953.
15. Nelson DB et al. Bacterial vaginosis in pregnancy: current findings and future directions. Epidemiol Rev. 2002;24(2):102-108.
16. Moi H. Prevalence of bacterial vaginosis and its association with genital infections, inflammation and contraceptive methods in women attending sexually transmitted disease and primary health clinics. Int J STD AIDS. 1990;1:86–94.
17. Marrazzo JM et al. Safety and efficacy of a novel vaginal anti-infective, TOL-463, in the treatment of bacterial vaginosis and vulvovaginal candidiasis: a randomized, single-blind, phase 2, controlled trial. Clin Infect Dis. 2019;68(5):803-809.
18. Hensel KJ et al. Pregnancy-specific association of vitamin D deficiency and bacterial vaginosis. Am J Obstet Gynecol. 2011;204(1):e1-41.e419.
19. Allsworth JE et al. Severity of bacterial vaginosis and the risk of sexually transmitted infection. Am J Obstet Gynecol. 2011;205(2):113.e1-113.e1136.
20. Culhane JF et al. Maternal stress is associated with bacterial vaginosis in human pregnancy. Matern Child Health J. 2001;5(2):127-134.
21. Amabebe E et al. The vaginal microenvironment: the physiologic role of lactobacilli. Front Med (Lausanne). 2018;5:181.
22. Koumans EH et al. The prevalence of bacterial vaginosis in the United States, 2001-2004; associations with symptoms, sexual behaviors, and reproductive health. Sex Transm Dis. 2007;34(11):864-869.
23. McKinnon et al. The evolving facets of bacterial vaginosis: implications for HIV transmission. AIDS Res Hum Retrovir. 2019;35(3):219-228.
24. Cherpes et al. Association between acquisition of herpes simplex virus type 2 in women and bacterial vaginosis. Clin Infect Dis. 2003;37:319–325.
25. Wiesenfeld et al. Bacterial vaginosis is a strong predictor of Neisseria gonorrhoeae and Chlamydia trachomatis infection. Clin Infect Dis. 2003;36:663–668.
26. Dareng EO et al. Prevalent high-risk HPV infection and vaginal microbiota in Nigerian women. Epidemiol Infect. 2015:1–15.
27. Atashili J et al. Bacterial vaginosis and HIV acquisition: a meta-analysis of published studies. 2008;22(12):1493–1501.
28. Sharami SH et al. Urinary tract infections in pregnant women with bacterial vaginosis. J Obstet Gynaecol. 2007;27(3):252-254.
29. Afrakhteh M et al. Relationship between bacterial vaginosis and urinary tract infection. J Zanjan Univ Med Sci H Serv. 2003;42:37–42.
30. Harmanli OH et al. Urinary tract infections in women with bacterial vaginosis. Obstet Gynecol (NY 1953). 2000;95(5):710-712.
31. Zevin AS et al. Microbiome composition and function drives wound-healing impairment in the female genital tract. PLoS Pathog. 2016;12(9):e1005889-e1005889.
32. Suehiro TT et al. Association of human papillomavirus and bacterial vaginosis with increased risk of high-grade squamous intraepithelial cervical lesions. Int J Gynecol Cancer. 2019;29(2):242-249.
33. Ravel J et al. Bacterial vaginosis and its association with infertility, endometritis, and pelvic inflammatory disease. Am J Obstet Gynecol. 2021;224(3):251-257.
34. Damke E et al. Male partners of infertile couples with seminal positivity for markers of bacterial vaginosis have impaired fertility. Am J Mens Health. 2018;12(6):2104-2115.
35. He Y et al. Evaluation of the inhibitory effects of Lactobacillus gasseri and Lactobacillus crispatus on the adhesion of seven common lower genital tract infection-causing pathogens to vaginal epithelial cells. Front Med (Lausanne). 2020;7:284.
36. Wiesenfeld et al. Lower genital tract infection and endometritis: insight into subclinical pelvic inflammatory disease. Am J Obstet Gynecol. 2002;100(3):456-463.
37. Soper DE et al. Observations concerning the microbial etiology of acute salpingitis. Am J Obstet Gynecol. 1994;170:1008–1014.
38. Hillier SL et al. Role of bacterial vaginosis-associated microorganisms in endometritis. Am J Obstet Gynecol. 1996;175:435– 441.
39. Moreno I et al. Evidence that the endometrial microbiota has an effect on implantation success or failure. Am J Obstet Gynecol. 2016;215(6):684-703.
40. Ralph et al. Influence of bacterial vaginosis on conception and miscarriage in the first trimester: cohort study. BMJ. 1999;319:220-223.
41. Silver HM et al. Evidence relating bacterial vaginosis to intraamniotic infection. Am J Obstet Gynecol. 1989;161:808–812.
42. Kurki T et al. Bacterial vaginosis in early pregnancy and pregnancy outcome. Obstet Gynecol. 1992;80:173–177.
43. Hillier SL et al. Association between bacterial vaginosis and preterm delivery of a low- birth-weight infant. N Engl J Med.1995;333:1737–1742.
44. Gratocos E et al. Spontaneous recovery of bacterial vaginosis during pregnancy is not associated with an improved perinatal outcome. Acta Obstet Gynecol Scand. 1998;77:37–40.
45. Meis PJ et al. The preterm prediction study: significance of vaginal infections. Am J Obstet Gynecol. 1995;173:1231–1235.
46. Goldenberg RL et al. The preterm prediction study: fetal fibronectin, bacterial vaginosis, and peripartum infection. Obstet Gynecol. 1996;87:656–660.
47. Persson E et al. Infections after hysterectomy. A prospective nation-wide Swedish study. The Study Group on Infectious Diseases in Obstetrics and Gynecology within the Swedish Society of Obstetrics and Gynecology. Acta Obstet Gynecol Scand. 1996;75(8):757-761.
48. Bilardi J et al. Women’s management of recurrent bacterial vaginosis and experiences of clinical care: a qualitative study. PLoS One. 2016;11(3): e0151794.
49. Muzny CA et al. The role of antimicrobial resistance in refractory and recurrent bacterial vaginosis and current recommendations for treatment. Antibiotics (Basel). 2022;11(4):500.
50. Bradshaw CS et al. Current treatment of bacterial vaginosis-limitations and need for innovation. J Infect Dis. 2016;214:S14-S20.
51. Ravel J et al. Bacterial vaginosis and its association with infertility, endometritis, and pelvic inflammatory disease. Am J Obstet Gynecol. 2021;224(3):251-257.
52. Li T et al. Antimicrobial susceptibility testing of metronidazole and clindamycin against gardnerella vaginalis in planktonic and biofilm formation. Can J Infect Dis Med Microbio. 2020;2020:1361825-1361827.
53. Beigi RH et al. Antimicrobial resistance associated with the treatment of bacterial vaginosis. Am J Obstet Gynecol. 2004;191(4):1124-1129.
54. Bagnall P et al. Bacterial vaginosis: a practical review. JAAPA. 2017;30(12):15-21.
55. Nagaraja P et al. Antibiotic resistance of Gardnerella vaginalis in recurrent bacterial vaginosis. Indian J Med Microbiol. 2008;26(2):155-157.
56. McMillan et al. Disruption of urogenital biofilms by lactobacilli. Colloids Surf B Biointerfaces. 2011;86(1):58-64.
57. Hummelen R et al. Deep sequencing of the vaginal microbiota of women with HIV. PLoS One. 2010;58:12078.
58. Sobel R et al. Metronidazole for the treatment of vaginal infections. Expert Opin Pharmacother. 2015;16(7):1109-1115.
59. Bannatyne RM et al. Recurrent bacterial vaginosis and metronidazole resistance in Gardnerella vaginalis. Sex Transm Infect. 1998;74:455–456.
60. Swidsinski A et al. Polymicrobial Gardnerella biofilm resists repeated intravaginal antiseptic treatment in a subset of women with bacterial vaginosis: a preliminary report. Arch Gynecol Obstet. 2015;291(3):605-609.
61. Eschenbach DA. Bacterial vaginosis: resistance, recurrence, and/or reinfection? Clin Infect Dis. 2007;44:220–221.
62. Klebanoff MA et al. Personal hygienic behaviors and bacterial vaginosis. Sex Transm Dis. 2010;37(2):94-99.
63. Plummer EL et al. A prospective, open-label pilot study of concurrent male partner treatment for bacterial vaginosis. MBio. 2021;12(5):e
64. Plummer EL et al. Combined oral and topical antimicrobial therapy for male partners of women with bacterial vaginosis: Acceptability, tolerability and impact on the genital microbiota of couples – a pilot study. PloS One. 2018;13(1):e0190199-e0190199.
65. Amaya-Guio J et al. Antibiotic treatment for the sexual partners of women with bacterial vaginosis. Cochrane Database Syst Rev. 2016;10(10):CD011701.

Angela Kelly, MA and Michael Stanclift, ND
In part one of this three-part series, we’ll discuss a healthy vaginal microbiome, symptoms, and the diagnostic criteria of bacterial vaginosis (BV).

A healthy vaginal microbiome
The vaginal microbiome is the lesser-known heroine of the body’s microbiomes and the first line of defense against pathogens that can cause infections.1-5 Like the gut microbiome, the vaginal microbiome is seeded from mother to daughter and the surrounding environment within 24 hours of birth.6-7Hormonal fluctuations related to puberty, the menstrual cycle, pregnancy, and menopause each contribute to the constantly changing landscape of the vaginal microbiome.8

During the reproductive years, the vaginal vault is populated by 90–95% lactobacilli in a balanced, healthy state. 9-10 Vaginal epithelial cells deposit glycogen, and the “friendly” lactobacilli ferment the polysaccharide, producing lactic acid.11 This fermentation process serves to lower vaginal pH, inhibit potentially harmful anaerobes’ growth, and discourage pathogens’ attachment to the vaginal epithelium.11 Additionally, lactobacilli produce antimicrobials such as hydrogen peroxide and bacteriocins, which deter biofilms and keep pathogenic anaerobes dormant.11 But what happens when the bacterial balance of the vagina is thrown out of whack?

Bacterial vaginosis characteristics
Bacterial vaginosis (BV) is the often silent, sometimes maddening, and quite common vaginal microbiome dysbiosis that affects 29.2% of women of reproductive age in the United States.12 The dysbiosis of BV is characterized by decreased “friendly” lactobacilli and an overgrowth of potentially pathogenic bacteria that may multiply to 1,000-10,000 times normal levels.13 Many studies suggest asymptomatic BV poses serious threats to reproductive and urogenital health and increases the risk of contracting and transmitting STIs.9,14-15 While the exact cause of BV is still under debate, the initial disruption of the vaginal microbiome is likely due to sexual transmission.16-17 Although with significantly lower frequency, females who have never been sexually active can also develop BV.18

BV is found globally, with higher incidences in certain countries and ethnicities.9 In the United States, Black and Mexican-American women are more likely to be affected by BV.9,19-20 Despite being the most common vaginal dysbiosis, women’s awareness of BV prior to their first infection is very low.21

Symptoms of bacterial vaginosis and diagnostic criteria
While most BV cases occur asymptomatically, the CDC describes the following common symptoms that may occur:12,22

• A thin white or gray vaginal discharge
• Pain, itching, or burning in the vagina
• A strong fish-like odor, especially after sex
• Burning when peeing
• Itching around the outside of the vagina

BV can be diagnosed using Amsel’s criteria or the Nugent scoring system.

Amsel’s criteria for the diagnosis of BV are met when 3 out of 4 of the following clinical signs are present:23

1. Abnormal vaginal discharge
2. Amine (fish-like) odor when vaginal fluid is exposed to 10% potassium hydroxide (KOH)
3. Clue cells on wet mount
4. Vaginal pH > 4.5

Alternatively, the Nugent scoring system can be used to diagnose BV using a Gram stain, microscope, and a 0-10 score based on the amounts of the following microorganisms seen per high-powered field:24

• Curved rods (Mobiluncus species morphotypes)
• Gram variable rods (Garderella vaginalis morphotypes)
• Lactobacillus morphotypes

So now that we have some of the basic background knowledge of the vaginal microbiome and how to detect BV in our patients, part two of this series will look at causes and risk factors, health impacts, and current conventional therapies for BV. In part three, we’ll look at alternative and emerging treatments, the role of probiotics, and discuss the mechanisms behind these approaches.

Citations

1. Brotman RM. Vaginal microbiome and sexually transmitted infections: An epidemiologic perspective. J Clin Invest. 2011;121(12):4610-4617.
2. Graver MA et al. The role of acidification in the inhibition of Neisseria gonorrhoeae by vaginal lactobacilli during anaerobic growth. Ann Clin Micro Antimicrob. 2011;10(1):8-8.
3. O’Hanlon DE et al. In vaginal fluid, bacteria associated with bacterial vaginosis can be suppressed with lactic acid but not hydrogen peroxide. BMC Inf Dis. 2011;11(1):200.
4. Gong Z et al. Lactobacilli inactivate Chlamydia trachomatis through lactic acid but not H2O2. PloS One. 2014;9(9):e107758-e107758.
5. Nunn KL et al. Enhanced trapping of HIV-1 by human cervicovaginal mucus is associated with Lactobacillus crispatus-dominant microbiota. MBio. 2015;6(5):1-9.
6. Rotimi VO et al. The development of the bacterial flora in normal neonates. J Med Microbiol. 1981;14:51-62.
7. Borges S et al. The role of lactobacilli and probiotics in maintaining vaginal health. Arch Gynecol Obstet. 2014;289(3):479–895.
8. Joseph RJ et al. Finding a balance in the vaginal microbiome: how do we treat and prevent the occurrence of bacterial vaginosis? Antibiotics (Basel). 2021;10(6):719.
9. Coudray MS et al. Bacterial vaginosis-a brief synopsis of the literature. Eur J Obstet Gynecol Reprod Biol. 2020;245:143-148.
10. Bautista CT et al. Association of bacterial vaginosis with chlamydia and gonorrhea among women in the U.S. army. Am J Prev Med. 2017;52(5):632-639.
11. Amabebe E et al. The vaginal microenvironment: the physiologic role of lactobacilli. Front Med (Lausanne). 2018;5:181.
12. Koumans EH et al. The prevalence of bacterial vaginosis in the United States, 2001-2004; associations with symptoms, sexual behaviors, and reproductive health. Sex Transm Dis. 2007;34(11):864-869.
13. Larsson PG et al. Diagnosis of bacterial vaginosis: need for validation of microscopic image area used for scoring bacterial morphotypes. Sex Transm Infect. 2004;80(1):63-67.
14. McKinnon et al. The evolving facets of bacterial vaginosis: implications for HIV transmission. AIDS Res Hum Retrovir. 2019;35(3):219-228.
15. Allsworth JE et al. Severity of bacterial vaginosis and the risk of sexually transmitted infection. Am J Obstet Gynecol. 2011;205(2):113.e1-113.e1136.
16. Zozaya M et al. Bacterial communities in penile skin, male urethra, and vaginas of heterosexual couples with and without bacterial vaginosis. Microbiome. 2016;4(16):16.
17. Liu CM et al. Penile microbiota and female partner bacterial vaginosis in Rakai, Uganda. 2015;6:e00589.
18. Yen S et al. Bacterial vaginosis in sexually experienced and non-sexually experienced young women entering the military. Obstet Gynecol. 2003;102:927–933.
19. Ness S et al. Can known risk factors explain racial differences in the occurrence of bacterial vaginosis? J Natl Med Assoc. 2003;95:201-212.
20. https://www.cdc.gov/std/bv/stats.htm. Accessed September 19, 2022.
21. Bilardi J et al. Women’s management of recurrent bacterial vaginosis and experiences of clinical care: a qualitative study. PLoS One. 2016;11(3):
22. https://www.cdc.gov/std/bv/stdfact-bacterial-vaginosis.htm. Accessed September 19, 2022.
23. Amsel R et al. Nonspecific vaginitis. Diagnostic criteria and microbial and epidemiological associations. Am J Med. 1983;74:14-22.
24. Udayalaxmi J et al. Comparison of the methods of diagnosis of bacterial vaginosis. J Clin Diag Res. 2011;5(3):498–501.

A growing to-do list, meetings that drag into the late evening, financial strains, relationship issues, trouble sleeping: When it comes to stress, many men struggle to find an outlet. Yet, without the right coping mechanisms, chronic stress can deeply, and adversely, affect men’s health.1

How can men reduce the stress in their lives?
No matter the source, chronic stress has significant effects on the body. Studies have linked it to a variety of health issues involving mood, sleep, appetite, and more.1 And while researchers have yet to pinpoint the specific ways long-term stress affects the heart, and other systems, men under seemingly constant pressure are also more likely to eat unhealthy foods, adopt a sedentary lifestyle, and smoke.2
​
Fortunately, men don’t have to let stress get the better of them. There are a number of strategies men can leverage to take charge of their wellbeing. Here are three stress-busting tips men should know about:

Exercise on a near-daily basis

• Only 21.9% of adults in the US make time for light-to-moderate exercise at least five days a week.3 Some men feel they need to achieve the impossible in their personal and professional lives and often let physical activity fall to the wayside. However, exercise produces mood-elevating chemicals that relieve stress.3 In addition, physical activity helps lower blood pressure, strengthen the heart muscle, and promote a healthy weight.4 These improved outcomes may also increase productivity.
• Men might consider taking just 20 minutes to perform a few sets of crunches, jumping jacks, and burpees. Or cut back on electronics and go on a walk during the time they would have spent scrolling through social media feeds. It will quickly be evident that it is possible to enjoy a flexible, rewarding fitness routine. Even short spurts of exercise can go a long way.

Improve diet and consider supplementation

• Good nutrition helps the body recover from stress. And while of course we’d like to emphasize the importance of a balanced, nutrient-rich diet, supplementation is also a strategy to consume more of certain nutrients that can support the body’s stress response.

Accordingly, we suggest that men look into the following dietary supplements:

• MetaRelax® features an appealing orange citrus flavor in a dissolvable stick pack and promotes a positive mood, restful sleep, and relaxation.*
• Adreset® is designed to support resilience and stamina in individuals who are feeling mild weakness and fatigue due to stress.*
• NuSera® is a chocolate-flavored chewable featuring Lactium, which research suggests promotes a healthy response to stress.*
• Exhilarin® offers a formula rooted in Ayurvedic tradition, designed to help support energy and stress tolerance.*

• Adrenogen® pairs raw adrenal concentrate with select B vitamins to encourage a healthy adrenal function.*

Change the things that can be changed (and accept those that cannot be changed)

• Stress generally involves feeling overwhelmed or out of control. An ideal stress-busting solution is to adjust one’s outlook by addressing stressors that are within your control and letting go of the things that cannot be changed. For instance, maybe you can’t change the length of your commute—but you can spend the hour listening to an inspiring podcast or generating ideas for an upcoming presentation.

• Similarly, if you aren’t getting the recommended eight hours of rest each night, make changes that can help you sleep more soundly. Reduce your caffeine intake and store your phone and laptop in another room. Figure out what’s adding to your stress and go right to the source.

References

1. Mariotti A. (2015). The effects of chronic stress on health: new insights into the molecular mechanisms of brain-body communication. Future science OA, 1(3), FSO23. doi:10.4155/fso.15.21.
2. Elder S. Admit It, Men: You’re Stressed. https://www.webmd.com/men/features/admit-it-men-youre-stressed. Accessed November 28, 2018.
3. Harvard Medical School Staff. 5 ways to de-stress and help your heart. Harvard Health Publishing, HEALTHbeat. https://www.health.harvard.edu/heart-health/5-ways-to-de-stress-and-help-your-heart. Accessed November 28, 2018.
4. Centers for Disease Control.Prevalence of self-reported physically active adults—United States. MMWR Morb Mortal Weekly Report. 2008;57:1297–300.