Lactobacillus iners: A Transitional Species with Ambiguous Clinical Significance
L. iners is fundamentally different from protective vaginal lactobacilli like L. crispatus—it functions as a transitional species that colonizes disturbed vaginal environments and offers substantially less protection against dysbiosis, bacterial vaginosis, and sexually transmitted infections. 1
Microbiological Characteristics
L. iners has the smallest genome among known vaginal Lactobacillus species, which limits its protective capabilities compared to L. crispatus, L. gasseri, and L. jensenii 1
Unlike other protective lactobacilli, L. iners produces only L-lactic acid (not the more protective D-lactic acid), and does not consistently produce hydrogen peroxide, which is a key antimicrobial defense mechanism 2
L. iners does not grow well on standard de Man-Rogosa-Sharpe agar but requires anaerobic growth on blood agar, which historically led to its underrecognition until molecular techniques became widespread 1
L. iners exhibits absolute dependence on exogenous L-cysteine for growth, lacking canonical cysteine biosynthesis pathways—a unique metabolic vulnerability not shared by L. crispatus 3
Clinical Significance in Vaginal Health
Presence in Both Health and Disease
L. iners is paradoxically found in both healthy vaginas and in high numbers during bacterial vaginosis, making it an unreliable marker of vaginal health 1
L. iners-dominated vaginal communities are associated with significantly higher risk of bacterial vaginosis compared to L. crispatus-dominated communities 3
Following standard metronidazole treatment for BV, L. iners typically becomes the dominant species, which likely contributes to the high recurrence rates (50-80% within one year) seen with BV 4, 3
Association with Adverse Outcomes
L. iners dominance is associated with increased susceptibility to sexually transmitted infections compared to communities dominated by L. crispatus 1
Vaginal microbiota dominated by L. iners correlates with adverse pregnancy outcomes, including preterm delivery and premature rupture of membranes 1
L. iners appears to function as an opportunistic pathogen under certain conditions, transitioning from commensal to contributor of dysbiosis when the vaginal environment is disrupted 1
Strain-Level Heterogeneity
L. iners exists as multiple strain combinations with widely varying functional repertoires, which explains its inconsistent associations with health outcomes 2
Standard 16S rRNA marker gene sequencing cannot capture strain-level resolution, meaning most published studies aggregate strain-specific effects and may yield imprecise risk estimates 2
Whole metagenome sequencing is required to understand the true functional diversity of L. iners strains and their differential impacts on vaginal health 2
Therapeutic Implications
Selective Targeting of L. iners
Novel bacteriocins (gassericin K7A and K7B) demonstrate highly selective inhibition of L. iners while sparing protective species like L. crispatus, with MICs as low as 2 ng/ml 5
Combining metronidazole with L. iners-selective bacteriocins completely eliminates both L. iners and Gardnerella vaginalis in coculture experiments while preserving L. crispatus 5
Cystine uptake inhibitors selectively suppress L. iners growth due to its unique cysteine dependence, offering another potential therapeutic target 3
Combining cystine uptake inhibitors with metronidazole promotes L. crispatus dominance in defined BV-like communities by preventing L. iners overgrowth 3
Probiotic Considerations
L. crispatus CTV-05 was rationally selected for vaginal probiotic use based on its predominance in healthy vaginas, though L. iners is arguably more commonly found 6
The selection of L. crispatus over L. iners for probiotic development reflects the understanding that natural predominance does not equal protective capacity 6
Key Clinical Pitfalls
Do not interpret L. iners dominance as a sign of vaginal health—unlike L. crispatus dominance, it represents an unstable intermediate state prone to dysbiosis 1
Standard BV treatment with metronidazole alone predictably results in L. iners overgrowth, which may explain why recurrence rates remain unacceptably high despite microbiological "cure" 3
Vaginal pH testing alone cannot distinguish between protective L. crispatus-dominated and less protective L. iners-dominated communities, as both can maintain acidic pH 7
Traditional culture methods will miss L. iners entirely, requiring molecular diagnostics or specialized anaerobic culture techniques for detection 1