Vaginal lactobacilli produce anti-inflammatory β-carboline compounds

The optimal vaginal microbiome is a Lactobacillus-dominant community. Apart from Lactobacillus iners, the presence of Lactobacillus species is associated with reduced vaginal inflammation and reduced levels of pro-inflammatory cytokines. Loss of Lactobacillus-dominance is associated with inflammatory conditions, such as bacterial vaginosis (BV). We have identified that Lactobacillus crispatus, a key vaginal bacterial species, produces a family of β-carboline compounds with anti-inflammatory activity. These compounds suppress nuclear factor κB (NF-κB) and interferon (IFN) signaling downstream of multiple pattern recognition receptors in primary human cells and significantly dampen type I IFN receptor (IFNAR) activation in monocytes. Topical application of an anti-inflammatory β-carboline compound, perlolyrine, was sufficient to significantly reduce vaginal inflammation in a mouse model of genital herpes infection. These compounds are enriched in cervicovaginal lavage (CVL) of healthy people compared with people with BV. This study identifies a family of compounds by which vaginal lactobacilli mediate host immune homeostasis and highlights a potential therapeutic avenue for vaginal inflammation. [Display omitted] •Identified β-carbolines (BCs) with anti-inflammatory activity in vaginal lactobacilli•BCs suppress TLR and IFNAR signaling in immune cells but only TLR in barrier cells•Topical BC treatment suppresses vaginal inflammation in mice•BCs are enriched in healthy people compared with people with BV How vaginal lactobacilli promote health and reduce inflammation remains unclear. Glick, Webber et al. identify a family of anti-inflammatory compounds produced by vaginal lactobacilli. β-carbolines suppress inflammatory signaling in cells, and topical application reduces vaginal inflammation in mice. These compounds are enriched in the vaginas of healthy people.