Hu Tianqi, Meng Ya, Zhao Changying, Sheng Dashuang, Yang Sijie, Dai Junhui, Wei Tiantian, Zhang Yiming, Zhao Guoping, Liu Yanan, Wang Qinghua, Zhang Lei
Microbiome-X, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan, China.
State Key Laboratory of Reproductive Medicine and Offspring Health, Center for Reproductive Medicine, Institute of Women, Children and Reproductive Health, Shandong University, Jinan, China.
Microbiol Spectr. 2025 Jun 3;13(6):e0298424. doi: 10.1128/spectrum.02984-24. Epub 2025 Apr 16.
As the predominant constituents of the vaginal microbiome in healthy women, species are considered essential in maintaining a homeostatic vaginal microbiome. Specific species can produce beneficial metabolites to support their persistence within the host environment and inhibit colonization. Due to the extensive diversity of species and their metabolites, comprehensively investigating all possible interactions remains challenging. This study employed an integrative approach combining genome-scale metabolic modeling, metagenomic sequencing, and validation to explore and interactions. Pairwise simulations of 159 strains with revealed that most strains exhibit inhibitory effects, altering fungal amino acid and carbohydrate metabolism. Key inhibitory metabolites identified included formate, L-lactate, and L-malate. Metagenomic analysis of vaginal swabs from 20 vulvovaginal candidiasis (VVC) patients and 20 healthy women showed a correlation between species abundance and reduced colonization. experiments confirmed the inhibitory effects of these metabolites and the selected strains on growth, thereby validating our computational predictions. These findings provide insights into the metabolic interactions within the vaginal microbiome and pave the way for targeted microbial or metabolite-based therapeutic strategies to manage VVC.IMPORTANCEVulvovaginal candidiasis is a prevalent fungal infection with significant implications for women's health, caused primarily by . Although the protective role of a -dominated vaginal microbiome is well established, the metabolic mechanisms underlying the interactions between species and remain inadequately understood. Specifically, the species that effectively inhibit and the metabolic pathways involved warrant further investigation. This study offers novel insights into the metabolic mechanisms underlying antagonism against . By identifying critical metabolic pathways and inhibitory metabolites, this study enhances our understanding of vaginal microbiome dynamics and host-microbe interactions. The findings suggest that key strains and their metabolites could significantly reduce harmful levels of , paving the way for future therapeutic strategies that leverage these microbial characteristics to promote vaginal health.
作为健康女性阴道微生物群的主要组成部分，[某种细菌]物种被认为对于维持阴道微生物群的稳态至关重要。特定的[某种细菌]物种可以产生有益的代谢产物，以支持它们在宿主环境中的持续存在并抑制[白色念珠菌]的定殖。由于[某种细菌]物种及其代谢产物具有广泛的多样性，全面研究所有可能的相互作用仍然具有挑战性。本研究采用了一种综合方法，结合基因组规模的代谢建模、宏基因组测序和[实验]验证，以探索[某种细菌]和[白色念珠菌]之间的相互作用。对159株[某种细菌]菌株与[白色念珠菌]的成对模拟显示，大多数菌株表现出抑制作用，改变了真菌的氨基酸和碳水化合物代谢。鉴定出的关键抑制性代谢产物包括甲酸、L-乳酸和L-苹果酸。对20名外阴阴道念珠菌病（VVC）患者和20名健康女性的阴道拭子进行的宏基因组分析表明，[某种细菌]物种丰度与[白色念珠菌]定殖减少之间存在相关性。[实验]证实了这些代谢产物和所选[某种细菌]菌株对[白色念珠菌]生长的抑制作用，从而验证了我们的计算预测。这些发现为了解阴道微生物群内的代谢相互作用提供了见解，并为基于微生物或代谢产物的靶向治疗策略管理VVC铺平了道路。
重要性
外阴阴道念珠菌病是一种常见的真菌感染，对女性健康有重大影响，主要由[白色念珠菌]引起。尽管以[某种细菌]为主的阴道微生物群的保护作用已得到充分证实，但[某种细菌]物种与[白色念珠菌]之间相互作用的代谢机制仍未得到充分了解。具体而言，有效抑制[白色念珠菌]的[某种细菌]物种及其涉及的代谢途径值得进一步研究。本研究为[某种细菌]对[白色念珠菌]的拮抗作用的代谢机制提供了新的见解。通过识别关键的代谢途径和抑制性代谢产物，本研究增强了我们对阴道微生物群动态和宿主-微生物相互作用的理解。研究结果表明，关键的[某种细菌]菌株及其代谢产物可以显著降低[白色念珠菌]的有害水平，为未来利用这些微生物特性促进阴道健康的治疗策略铺平了道路。
