Every year, millions of women seek treatment for bacterial vaginosis—yet more than half experience recurrence within six months. Growing evidence suggests one reason may be that clinicians are treating only half of a two-person problem.
The lower genital tract, which is most relevant to genital health and infection risk, consists of the vagina and cervix in females, and the penile glans, foreskin, coronal sulcus, and urethra in males. These sites represent dynamic mucosal ecosystems, and increasing evidence points to how the genital microbiome shapes local immunology, infection susceptibility, and reproductive outcomes. An optimal and protective vaginal microbiome is dominated by Lactobacillus crispatus, associated with lower vaginal pH (between 3.8–4.5), decreased inflammation, and increased protective innate factors. In contrast, bacterial vaginosis (BV) is characterized by a non-optimal vaginal microbiome marked by higher abundances of proinflammatory facultative anaerobes, and is associated with adverse clinical symptoms (i.e., vaginal discharge, malodour) and a 60% increase in acquisition risk for human immunodeficiency virus (HIV). Furthermore, non-optimal microbiomes also increase susceptibility for sexually transmitted infections (STI), enhanced urogenital inflammation, and pregnancy complications such as preterm birth. Although the penile microbiota is less studied, it is similarly associated with HIV risk, especially among uncircumcised men with anaerobe-rich penile microbiomes. Sexual partners also exchange microbiota and immune factors during condomless intercourse, making genital health and treatment a shared outcome.
Clinically, microbiome profiles may identify women at elevated risk of STIs and adverse reproductive health outcomes before symptoms arise. Unfortunately, however, such testing is not standard of care. Providers managing recurrent BV or repeat STI exposure should consider partner factors, not only individual treatment. We explore the clinical implications of non-optimal genital microbiomes in the following sections.
Optimal Lactobacillus dominance
Lactobacillus-rich communities protect the vaginal mucosa through acidification, antimicrobial peptides, epithelial barrier reinforcement, and immune modulation. L. crispatus promotes a more acidic vaginal pH at 3.5–4.5 via lactic acid production, while hydrogen peroxide and bacteriocins (antimicrobial peptides) further suppress pathogen growth and colonization. Critically, L. crispatus fortifies the vaginal epithelium by strengthening tight and adherens junctions between epithelial cells, limiting the penetration of viruses and bacteria into subepithelial tissue where cells prone to infection are often targeted. Not all Lactobacillus species are equal; L. crispatus is the most stable and protective against STI infections in the female genital tract, but other species (i.e., L. gasseri, L. iners, or L. jensenii) are also common but offer less protection. In turn, Lactobacillus iners is highly debated as a semi-pathogenic species, with its detection being linked to persistent BV and treatment failure rather than protection against microbiome dysbiosis. Its presence is usually linked to greater inflammation and the presence of other non-favourable bacterial species, and women with L. iners-dominant vaginal microbiotas warrant enhanced STI screening and preconception counselling even when asymptomatic.
Dysbiosis: ecosystem failure with reproductive and transmission consequences
A non-optimal vaginal microbiome, also known as bacterial vaginosis (BV), is characterized by decreased levels of Lactobacillus and an increased density of facultative anaerobes that are often associated with inflammation and adverse clinical outcomes like abnormal vaginal discharge, fishy odour, and irritation. The most common anaerobes detected in BV belong to the Gardnerella, Prevotella, Mobiluncus, and Megasphaera genera. Many women are asymptomatic despite carrying these proinflammatory anaerobes in the vagina, making clinical diagnosis and treatment decisions challenging.
On a molecular scale, BV is associated with elevated vaginal inflammation and HIV target cell recruitment to the vaginal epithelium. Vaginal epithelial damage, which could be due to mechanical trauma from sex, further create an activated, permeable environment that is susceptible to HIV, HSV-2, chlamydia, gonorrhoea, and HPV infection, as well as pelvic inflammatory disease. BV also impacts reproductive health and pregnancy outcomes, where non-optimal bacteria can travel upwards to the cervix/uterus, triggering inflammation and infections that are strongly linked to preterm birth. Clinically, these phenomena raise the risk of serious illness or death in newborns, long hospital stays, and long-term neurodevelopmental complications for infants born preterm.
In contrast to the largely singular bacterial niche of the vagina, the penis consists of distinct niches; the most relevant to HIV and STI risk are the subpreputial space (underlying the foreskin of uncircumcised men), which supports a high abundance of bacteria, as well as the foreskin, urethra, and glans, all of which represent significantly different risk to HIV and STI infections. Similar to the vagina, a non-optimal penile microbiome is one depleted of skin-type bacteria (i.e., Corynebacterium, Streptococcus species) and elevated in facultative anaerobe density. Voluntary medical male circumcision can reduce HIV acquisition risk by ~50–60%, with parallel reductions in anaerobic taxa, inflammation, foreskin target cells, and improved epithelial integrity. To date, no penile bacteria or immune factors have been identified as directly protective against male HIV susceptibility.
Team effort: couple-level prevention in genital health and microbiota optimization
While the male and female genital microbiomes may seem distinct, emerging evidence demonstrates that sexual partners exchange genital bacteria during condomless penile-vaginal sex, In fact, the penis acts as a reservoir for BV-associated bacteria that re-enter the vagina during sex, which can drive BV recurrence and vaginal inflammation. As such, a man’s penile microbiome accurately predicts BV recurrence in his female partner, where over 50% of men with detectable BV-associated bacteria on the penis have a BV-positive female partner. Therefore, there is increased recognition that optimization of the vaginal or penile microbiome requires considering both partners’ microbiota.
For example, penile circumcision effectively lowers male HIV risk by decreasing the abundance of pathogenic penile bacteria while also limiting the opportunity for BV-associated bacteria to be acquired during sex or transmitted to the female partner. More proactive interventions to optimize the vaginal microbiome include standard antibiotic treatment for BV (such as metronidazole or clindamycin) to eliminate BV-associated bacteria. However, antibiotics often lead to high failure rates, with more than 50% of treated women reporting BV recurrence 6 months later. Therefore, coupling antibiotics with L. crispatus live biotherapeutics can restore optimal bacteria in the vagina to prevent BV recurrence. Clinical trials have also show “protective” against HIV and STI infections to create a live biotherapeutic equivalent to Lactobacillus products in the vagina.
Jinny Tsang
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