美国哈佛医学院Douglas S. Kwon等研究人员合作发现，阴道乳酸杆菌脂肪酸反应机制揭示针对代谢物的细菌性阴道病治疗策略。2024年8月19日，国际知名学术期刊《细胞》在线发表了这一成果。

研究人员表示，细菌性阴道病（BV），一种以乳酸杆菌缺乏为特征的常见综合症，与不良健康结果相关。BV在标准抗生素治疗后经常复发，部分原因是抗生素促进了Lactobacillus iners的微生物群主导地位，而不是Lactobacillus crispatus，这种菌株具有更有利的健康关联。因此，需要促进L. crispatus和抑制L. iners的策略。

研究人员发现，油酸（OA）和类似的长链脂肪酸能够同时抑制L. iners和增强L. crispatus的生长。这些表型需要OA诱导的基因，这些基因在L. crispatus和相关的乳酸杆菌中保守，包括油酸水合酶（ohyA）和推测的脂肪酸外排泵（farE）。FarE介导了对OA的抗性，而OhyA在阴道微生物群中活性强，通过生化方式将OA隔离为仅ohyA携带的生物体可以利用的衍生形式，从而提高了细菌的适应性。OA在体外BV模型中比抗生素更有效地促进了L. crispatus的主导地位，表明代谢物基础的治疗方法可能是一种有效的干预策略。

附：英文原文

Title: Vaginal Lactobacillus fatty acid response mechanisms reveal a metabolite-targeted strategy for bacterial vaginosis treatment

Author: Meilin Zhu, Matthew W. Frank, Christopher D. Radka, Sarah Jeanfavre, Jiawu Xu, Megan W. Tse, Julian Avila Pacheco, Jae Sun Kim, Kerry Pierce, Amy Deik, Fatima Aysha Hussain, Joseph Elsherbini, Salina Hussain, Nondumiso Xulu, Nasreen Khan, Vanessa Pillay, Caroline M. Mitchell, Krista L. Dong, Thumbi Ndungu, Clary B. Clish, Charles O. Rock, Paul C. Blainey, Seth M. Bloom, Douglas S. Kwon

Issue&Volume: 2024-08-19

Abstract: Bacterial vaginosis (BV), a common syndrome characterized by Lactobacillus-deficient vaginal microbiota, is associated with adverse health outcomes. BV often recurs after standard antibiotic therapy in part because antibiotics promote microbiota dominance by Lactobacillus iners instead of Lactobacillus crispatus, which has more beneficial health associations. Strategies to promote L. crispatus and inhibit L. iners are thus needed. We show that oleic acid (OA) and similar long-chain fatty acids simultaneously inhibit L. iners and enhance L. crispatus growth. These phenotypes require OA-inducible genes conserved in L. crispatus and related lactobacilli, including an oleate hydratase (ohyA) and putative fatty acid efflux pump (farE). FarE mediates OA resistance, while OhyA is robustly active in the vaginal microbiota and enhances bacterial fitness by biochemically sequestering OA in a derivative form only ohyA-harboring organisms can exploit. OA promotes L. crispatus dominance more effectively than antibiotics in an in vitro BV model, suggesting a metabolite-based treatment approach.

DOI: 10.1016/j.cell.2024.07.029

Source: https://www.cell.com/cell/fulltext/S0092-8674(24)00823-7