Lactic Acid’s Untapped Potential to Optimise the Vaginal Microbiota and Mucosal Environment

April 8, 2026 Professor Gilda Tachedjian BSc (Hons) PhD Editor's Choice, Pharma & Human Health
Professor Gilda Tachedjian BSc (Hons) PhD

Head, Life Sciences Discipline

Burnet Institute

Across women’s health, there is growing recognition of the urgent need for antibiotic‑sparing strategies that restore and sustain an optimal vaginal microbiota. Such an ecosystem is typically dominated by Lactobacillus crispatus, a species strongly associated with reduced risk of sexually transmitted infections (STIs), improved reproductive outcomes, and protection against adverse obstetric outcomes1. Yet for millions of women worldwide, this optimal state is disrupted2.

Vaginal dysbiosis—most commonly presenting as bacterial vaginosis (BV)—is characterised by a depletion of protective lactobacilli and an overgrowth of obligate and facultative anaerobes1. BV affects approximately one in three women of reproductive age globally2. While often asymptomatic, its clinical and public‑health consequences are substantial. BV is associated with increased genital inflammation, heightened susceptibility to HIV and other STIs, an increased risk of cervical dysplasia, and a significantly elevated likelihood of spontaneous preterm birth 1,3.

The Limitations of Current Approaches

Standard treatment for symptomatic BV relies on antibiotics such as metronidazole or clindamycin3. Although these therapies often provide short‑term resolution, recurrence rates remain extraordinarily high—up to 60% within six months when male partners are not treated3. More importantly, antibiotic therapy rarely restores the vaginal microbiota to a L. crispatus‑dominated state. Instead, women typically transition to a microbiota dominated by Lactobacillus iners, a species frequently associated with BV, microbial instability, and reduced protection4,5.

Given these limitations—and the absence of approved treatments for asymptomatic vaginal dysbiosis—there is growing interest in strategies that directly repopulate the vagina with L. crispatus. These include vaginally administered live biotherapeutic products (LBPs)6,7,8 and vaginal microbiome transplants (VMTs) from donors with optimal microbiota9. Most approaches follow a “weed-and-seed” strategy, using antibiotics to disrupt and reduce the existing microbial community before introducing beneficial lactobacilli6,7. While promising, this approach has important limitations: not all women can be successfully colonised with L. crispatus, and even when colonisation occurs, it may not persist after treatment ends.

The use of antibiotics solely for “weeding” also presents challenges. BV‑associated bacteria can exhibit resistance to antibiotics, such as metronidazole, that do not eliminate L. iners, which often occupies the ecological niche post‑treatment. As a result, alternative approaches are being exploring, including selective agents such as oleic acid to target L. iners10, and broad‑spectrum antiseptics like chlorhexidine11—although these may be harsh on the cervicovaginal mucosa.

Here, I propose an alternative strategy: harnessing lactic acid as a biologically active, mucosa‑compatible agent for both microbial reduction “weeding” and long-term maintenance. This approach could be used before seeding with L. crispatusand periodically thereafter—such as after sexual activity or menses—to help sustain a protective microbiota.

Lactic Acid: More Than a Vaginal Acidifier

In an optimal vaginal microbiota, L. crispatus produces lactic acid that acidifies the vaginal environment to around pH 3.812. Crucially, the biologically active form is protonated lactic acid, which predominates at pH <3.86. In contrast, in women with BV, vaginal pH is elevated (>4.5), and lactic acid exists mainly as the lactate anion, which lacks the same biological activity12.

  1. L. crispatus produces both D‑ and L‑isomers of lactic acid, whereas L. iners produces only the L‑isomer and at lower total concentrations12. This difference in lactic acid production may provide an opportunity to selectively suppress L. iners while preserving L. crispatus.

Importantly, lactic acid is not simply an acidifier. It exhibits potent, irreversible in vitro virucidal activity against HIV—far exceeding the effects of low pH alone or other vaginal acids such as acetic, propionic, and butyric acids, which predominate in BV13. Enhanced trapping of HIV in cervicovaginal mucus is strongly associated with L. crispatus dominance14, and intrinsic lactic acid in cervicovaginal fluid is a key mediator of anti-HIV activity15.

Immunobiological Benefits

Beyond its antimicrobial effects, lactic acid directly modulates the cervicovaginal epithelium. In vitro, lactic acid has been shown to:

  • Suppress pro‑inflammatory cytokines associated with increased HIV risk16
  • Strengthen epithelial barrier integrity, potentially reducing susceptibility to pathogen penetration17
  • Render epithelial cells less susceptible to Chlamydia trachomatis infection18
  • Exert effects that are more potent than media acidified to the same pH with HCl13,16,17

Notably, these benefits require only brief exposure (as little as 30 minutes) and persist for up to 24 hours16,17.

A Targeted Weeding Strategy

Lactic acid’s bactericidal activity is significantly more potent than low pH alone and more effective than other vaginal acids19. This earlier study showed that lactic acid kills a broad range of BV‑associated bacteria while sparing vaginal lactobacilli, including L. iners19. However, our recent work under physiological anaerobic conditions reveals a more nuanced picture.

We found that under these conditions, lactic acid can kill L. iners while sparing L. crispatus20. In mixed cultures containing Gardnerella vaginalis, L. iners, and L. crispatus, lactic acid shifted the competitive balance decisively in favour of L. crispatus20. In the absence of lactic acid, G. vaginalis and L. iners dominated. These findings were determined using taxon‑specific PCR assays that detect viable bacteria20.

Moreover, combining lactic acid with metronidazole suppressed BV‑associated bacteria and L. iners20, suggesting a weeding strategy that could enhance subsequent seeding with L. crispatus.

The Gap: Lack of High‑Quality In Vivo Evidence

Despite compelling in vitro data, robust clinical evidence remains limited3. Many currently available lactic acid‑containing vaginal gels are hyperosmolal and have been shown to be cytotoxic and/or pro‑inflammatory in a validated 3‑D human vaginal tissue model. This raises safety concerns and complicates efforts to evaluate the true biological potential of lactic acid in vivo21. In addition, no high‑quality studies have assessed lactic acid–metronidazole combinations using molecular microbiome characterisation.

A Next‑Generation Lactic Acid Gel

To address these gaps, we have developed a next‑generation lactic acid vaginal gel along with a matched placebo, specifically formulated to be safe and non‑inflammatory in a validated 3‑D human vaginal tissue model. Preclinical studies are nearing completion. We have completed a pharmacokinetic study in a sheep vaginal model—which closely mimics human vaginal anatomy—to determine optimal dosing to achieve lactic acid concentrations sufficient to suppress BV‑associated bacteria and L. iners, while supporting conditions favourable for L. crispatus.

Our next step is to evaluate the safety of this formulation in women, laying the groundwork for future trials to assess its ability to optimise the vaginal microbiota and sustain L. crispatus dominance.

 

Citations

  1. McKinnon LR., et al 2019. The evolving facets of bacterial vaginosis: implications for HIV transmission. AIDS Res Hum Retroviruses 35(3):219-228
  2. Peebles K., et al 2019. High global burden and costs of bacterial vaginosis: a systematic review and meta-analysis. Sex Transm Dis 46(5): 204-311
  3. Bradshaw CS., et al 2025. Bacterial vaginosis. Nat Rev Dis Primers 11(1):43
  4. Munoz A., et al 2021. Modeling the temporal dynamics of cervicovaginal microbiota identifies targets that may promote reproductive health. Microbiome 9(1):163.
  5. Gosmann C., et al 2017. Lactobacillus-deficient cervicovaginal bacterial communities are associated with increased HIV acquisition in young South African women. Immunity 46(1): 29-37.
  6. Cohen CR., et al 2020. Randomized trial of Lactin-V to prevent recurrence of bacterial vaginosis. N Engl J Med 382(20): 1906-1915.
  7. Potloane D., et al 2026. VIBRANT: A phase I randomized trial of multi-strain vaginal L. crispatus live biotherapeutic products in people with bacterial vaginosis. Cell Host & Microbe March 18:S1931-3128(26)00084-3.
  8. Ravel J., et al 2025. Impact of a multi-strain L. crispatus-based vaginal symbiotic on the vaginal microbiome: a randomized placebo-controlled trial. NPJ Biofilms Microbiomes 11(1): 158
  9. Wronding T., et al (2023). Antibiotic-free vaginal microbiota transplant with donor engraftment, dysbiosis resolution and live birth after recurrent pregnancy loss: a proof of concept case study. eCinicalMedicine 61:102070.
  10. Zhu M., et al (2024). Vaginal Lactobacillus fatty acid response mechanisms reveal a metabolite-targeted strategy for bacterial vaginosis treatment. Cell 187(19):5413-5430.e29
  11. Wronding T., et al (2026). Vaginal microbiota transplantation for treatment of vaginal dysbiosis without the use of antibiotics: a double-blind randomised controlled trial in women with vaginal dysbiosis. Lancet Microbe. Mar 26:101294.
  12. Tachedjian G., et al (2017). The role of lactic acid production by probiotic Lactobacillus species in vaginal health. Res Microbiol 168(9-10):782-792.
  13. Aldunate M., et al (2025). Lactic acid produced by optimal vaginal Lactobacillus spp. potently and specifically inactivates HIV-1 in vitro by targeting the viral RNA genome and reverse transcriptase. PLoS Pathog 21(10): e1013594.
  14. Nunn KL., et al (2015). Enhanced trapping of HIV-1 by human cervicovaginal mucus is associated with Lactobacillus crispatus-dominant microbiota. mBio 6(5):e01084-15
  15. Tyssen D., et al (2018). Anti-HIV activity of lactic acid in human cervicovaginal fluid. mSphere 3(4):e00055-18.
  16. Hearps AC., et al (2017). Vaginal lactic acid elicits an anti-inflammatory response from human cervicovaginal epithelial cells and inhibits production of pro-inflammatory mediators associated with HIV acquisition. Mucosal Immunol. 10(6): 1480-1490.
  17. 17.Delgado-Diaz DJ., et al (2022). Lactic acid from vaginal microbiota enhances cervicovaginal epithelial barrier integrity by promoting tight junction protein expression. Microbiome 10(1): 141.
  18. Edwards VL., et al (2019). The cervicovaginal microbiota-host interaction modulates Chlamydia trachomatis infection. mBio 10(4): e01548-19.
  19. O’Hanlon DE., et al (2011). In vaginal fluid, bacteria associated with bacterial vaginosis can be suppressed with lactic acid but not hydrogen peroxide. BMC Infect Dis 11:200.
  20. Ellenberg P., et al (2024) Inhibitory activity of lactic acid isomers against L. iners and BV-associated vaginal bacteria to prevent HIV transmission. Abstract OA2203. Special Issue: Abstracts from HIVR4P 2024, the 5th HIV Research for Prevention Conference, 6 – 10 October, Lima, Peru & Virtual. J Int AIDS Soc; Suppl5:e26351
  21. Tyssen D., et al (2022). The impact of over-the-counter lactic acid containing vaginal gels on the integrity and inflammatory state of the vaginal epithelium in vitro. Front Reprod Health 4:915948.

Conflict of interest. I am a coinventor on a granted US patent on the immunomodulatory effects of lactic acid on cervicovaginal epithelial cells. I am also an inventor on a submitted patent application on a novel vaginal lactic acid gel formulation.