PDF(Pubmed)
Abstract：
The human microbiome contains genetic information that regulates metabolic processes in response to host health and disease. While acidic vaginal pH is maintained in normal conditions, the pH level increases in infectious vaginitis. We propose that this change in the vaginal environment triggers the biosynthesis of anti-vaginitis metabolites. Gene expression levels of Chryseobacterium gleum, a vaginal symbiotic bacterium, were found to be affected by pH changes. The distinctive difference in the metabolic profiles between two C. gleum cultures incubated under acidic and neutral pH conditions was suggested to be an anti-vaginitis molecule, which was identified as phenylacetic acid (PAA) by spectroscopic data analysis. The antimicrobial activity of PAA was evaluated in vitro, showing greater toxicity toward Gardnerella vaginalis and Candida albicans, two major vaginal pathogens, relative to commensal Lactobacillus spp. The activation of myeloperoxidase, prostaglandin E2, and nuclear factor-κB, and the expression of cyclooxygenase-2 were reduced by an intravaginal administration of PAA in the vaginitis mouse model. In addition, PAA displayed the downregulation of mast cell activation. Therefore, PAA was suggested to be a messenger molecule that mediates interactions between the human microbiome and vaginal health.
摘要：
人类微生物组包含调节代谢过程以响应宿主健康和疾病的遗传信息。虽然酸性阴道pH值维持在正常条件下，感染性阴道炎的pH值升高。我们认为阴道环境的这种变化会触发抗阴道炎代谢物的生物合成。回肠金黄杆菌的基因表达水平，一种阴道共生细菌，被发现受pH变化的影响。在酸性和中性pH条件下孵育的两种C.gleum培养物之间的代谢谱的独特差异被认为是抗阴道炎分子。通过光谱数据分析鉴定为苯乙酸（PAA）。体外评价PAA的抗菌活性，对阴道加德纳菌和白色念珠菌表现出更大的毒性，两种主要的阴道病原体，相对于共生乳杆菌属。髓过氧化物酶的激活，前列腺素E2和核因子-κB，在阴道炎小鼠模型中，阴道内给予PAA可降低环氧合酶-2的表达。此外,PAA显示肥大细胞活化的下调。因此,PAA被认为是介导人类微生物组和阴道健康之间相互作用的信使分子。
