Vaginal lactobacilli produce anti-inflammatory beta-carboline compounds

The optimal vaginal microbiome is a Lactobacillus-dominant, human-adapted community consistentlyfound in people around the world. Presence of Lactobacillus-dominant vaginal microbial communities,apart from Lactobacillus iners, is associated with reduced vaginal inflammation and reduced levels of pro-inflammatory cytokines. Loss of Lactobacillus-dominance is associated with inflammatory conditions suchas bacterial vaginosis. It remains unclear how health-associated lactobacilli actively promote the anti-inflammatory homeostasis of the vaginal mucosa. We have identified that Lactobacillus crispatusproduces a family of beta-carboline compounds with anti-inflammatory activity. These compounds suppressNFkB and interferon signaling downstream of multiple pattern recognition receptors in primary humancells and significantly dampen type I interferon receptor activation in monocytes. Topical vaginalapplication of an anti-inflammatory b-carboline compound, perlolyrine, was sufficient to significantlyreduce vaginal inflammation in a mouse model of genital herpes infection. These compounds areenriched in cervicovaginal lavage of healthy people compared to people with bacterial vaginosis