Protective Mechanisms of Vaginal Lactobacilli against Sexually Transmitted Viral Infections Original paper

What was reviewed?

This paper is a comprehensive narrative review that examined how vaginal lactobacilli protect against sexually transmitted viral infections by shaping the vaginal microenvironment, strengthening epithelial defenses, and modulating host immune responses. The authors synthesized molecular, microbiological, immunological, and clinical evidence to explain why Lactobacillus-dominated vaginal ecosystems are associated with reduced acquisition and persistence of viral pathogens, particularly human papillomavirus, human immunodeficiency virus, and herpes simplex virus. Rather than focusing on a single mechanism, the review emphasized a systems-level perspective in which microbial metabolites, epithelial barrier function, mucus integrity, and immune signaling act together to limit viral infectivity and inflammation.

Who was reviewed?

The review integrated data from multiple human populations, including healthy reproductive-age women, pregnant individuals, women with bacterial vaginosis or recurrent vulvovaginal infections, and cohorts at high risk for viral sexually transmitted infections. These clinical findings were supported by in vitro epithelial models, ex vivo human tissue systems, and animal studies designed to isolate specific microbial and immune mechanisms. By combining epidemiological associations with mechanistic experiments, the authors linked vaginal microbiota composition to clinically meaningful outcomes.

What were the most important findings?

The review established that vaginal lactobacilli exert antiviral protection through several converging mechanisms that extend beyond simple pathogen exclusion. Major microbial associations included Lactobacillus crispatus, Lactobacillus jensenii, Lactobacillus gasseri, and Lactobacillus vaginalis, which consistently correlated with lower prevalence and viral load of HPV, HIV, and HSV infections. Central to this protection was lactic acid production, which maintained vaginal pH at or below 4 and directly inactivated viral particles by destabilizing viral envelopes and fusion machinery. The authors highlighted that the D-lactic acid isomer, preferentially produced by L. crispatus, L. jensenii, and L. gasseri, preserved epithelial integrity by suppressing matrix metalloproteinases and reinforcing cell–cell adhesion. Hydrogen peroxide production by select Lactobacillus strains further contributed to virucidal activity and suppressed co-infecting bacteria that exacerbate inflammation.

Beyond direct antiviral effects, lactobacilli reduced epithelial permissivity to infection by enhancing tight junctions, maintaining mucus structure, and preventing degradation of protective mucins. Immunologically, lactobacilli dampened pro-inflammatory cytokines such as IL-6, IL-8, TNF-α, and RANTES while promoting antiviral interferon responses, thereby limiting immune activation that otherwise increases HIV susceptibility. In contrast, dysbiotic communities dominated by Gardnerella vaginalis, Prevotella, Atopobium, and Sneathia disrupted these defenses, raised vaginal pH, degraded mu

cus, and amplified inflammatory signaling, creating a permissive environment for viral transmission and persistence.

What are the greatest implications of this review?

For clinicians, this review underscores that vaginal viral susceptibility is tightly linked to microbial function rather than pathogen exposure alone. It supports therapeutic strategies that restore or preserve Lactobacillus-dominated ecosystems as adjuncts to antiviral prevention and treatment. Targeted probiotic or postbiotic approaches may reduce viral transmission risk while avoiding the collateral damage caused by repeated antimicrobial use.