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.

中文翻译：

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阴道乳酸杆菌产生抗炎 β-咔啉化合物


最佳的阴道微生物组是乳酸菌为主的群落。除了乳酸菌 iners 外，乳酸菌属的存在与阴道炎症的减少和促炎细胞因子水平的降低有关。乳酸菌优势的丧失与炎症状况有关，例如细菌性阴道病 （BV）。我们已经确定 Lactobacillus crispatus 是一种关键的阴道细菌物种，可产生具有抗炎活性的 β-咔啉化合物家族。这些化合物抑制原代人类细胞中多个模式识别受体下游的核因子 κB （NF-κB） 和干扰素 （IFN） 信号传导，并显著抑制单核细胞中 I 型 IFN 受体 （IFNAR） 的激活。局部应用抗炎 β-咔啉化合物 perlolyrine 足以显着减轻生殖器疱疹感染小鼠模型中的阴道炎症。与 BV 患者相比，这些化合物在健康人的宫颈阴道灌洗 （CVL） 中富集。本研究确定了阴道乳酸杆菌介导宿主免疫稳态的化合物家族，并强调了阴道炎症的潜在治疗途径。