Vaginal lactobacilli's anti-inflammatory superpowers

A healthy vaginal microbiome, typically dominated by Lactobacillus (sidenote: Lactobacillus A group of beneficial bacteria commonly found in the vaginal microbiome. They produce lactic acid, helping maintain a low pH to protect against infections. ) species, is central to gynecological health. Yet, the mechanisms through which these microbes modulate inflammation have long eluded researchers. A new study ¹ led by Virginia J. Glick, published in Cell Host & Microbe, unveils that certain strains of Lactobacillus crispatus produce β-carboline alkaloids - small molecules that exhibit targeted anti-inflammatory properties.

This discovery offers a fresh perspective on how these bacteria contribute to immune homeostasis and sets the stage for potential therapeutic applications.

β-carbolines: Precision immunomodulators

The study identified β-carboline compounds, including perlolyrine (BC6) (sidenote: Perlolyrine (BC6) A potent β-carboline compound identified in Lactobacillus crispatus that reduces inflammation while preserving immune defense. ) , as potent suppressors of inflammatory signaling. Using a dual reporter system in human monocyte-derived THP1 cells, researchers demonstrated that L. crispatus-derived β-carbolines inhibited NF-kB and type I interferon (sidenote: Interferon (IFN) Signaling A key immune pathway that fights infections but can drive inflammation when overactive. ) (IFNAR) pathways. These molecules uniquely suppressed pro-inflammatory cytokine production in immune cells while leaving antiviral responses intact in epithelial and barrier cells - a level of selectivity rare among anti-inflammatory agents.

Notably, this is the first time that β-carboline, previously linked to plants and soil microbes, have been identified as products of vaginal Lactobacillus strains. Their discovery highlights a new dimension in microbiota-host interactions. Furthermore, cervicovaginal lavage samples from individuals with healthy vaginal microbiomes (low Nugent scores (sidenote: Nugent score A diagnostic scoring system used to assess bacterial vaginosis based on the presence and proportions of certain bacteria in a Gram-stained vaginal sample. ) ) were significantly enriched with β-carboline compared to those with bacterial vaginosis (sidenote: Bacterial vaginosis Bacterial vaginosis (BV) is a type of vaginal inflammation caused by an imbalance of the bacterial species that are normally present in the vagina. ) (high Nugent scores), underscoring their potential as biomarkers for microbiome health.

Translating science into therapeutics

To explore the clinical relevance of these compounds, researchers applied BC6 topically in a mouse model of vaginal inflammation induced by herpes simplex virus-2 (HSV-2). The results were striking:

• BC6 significantly reduced inflammation
• Dampened pro-inflammatory cytokines like IL-1β and IL-18
• And improved disease scores without affecting viral titers

The treatment maintained innate immune cell populations while decreasing the inflammatory signaling driving tissue damage.

Even more intriguing, some mice pre-treated with L. crispatus supernatant remained asymptomatic despite similar viral burdens as untreated controls. This suggests a role for these compounds in enhancing disease tolerance - a concept gaining traction in immunological research.