Factors shaping vaginal microbiota long-term community dynamics in young adult women.

Tsukushi Kamiya, Nicolas Tessandier, Baptiste Elie, Claire Bernat, Vanina Boué, Sophie Grasset, Soraya Groc, Massilva Rahmoun, Christian Selinger, Michael S Humphrys, Marine Bonneau, Christelle Graf, Vinccent Foulongne, Jacques Reynes, Vincent Tribout, Michel Segondy, Nathalie Boulle, Jacques Ravel, Carmen Lía Murall, Samuel Alizon
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Abstract

The vaginal microbiota is known to affect women's health. Yet, there is a notable paucity of high-resolution follow-up studies lasting several months, which would be required to interrogate the long-term dynamics and associations with demographic and behavioural covariates. Here, we present a high-resolution longitudinal cohort study of 125 women, followed for a median duration of 8.6 months, with a median of 11 samples collected per woman. Using a hierarchical Bayesian Markov model, we characterised the patterns of vaginal microbiota community persistence and transition, simultaneously estimated the impact of 16 covariates and quantified individual variability among women. We showed that "optimal" (Community State Type (CST) I, II, and V) and "sub-optimal" (CST III) communities are more stable over time than "non-optimal" (CST IV) ones. Furthermore, we found that some covariates - most notably alcohol consumption - impacted the probability of shifting from one CST to another. We performed counterfactual simulations to confirm that alterations of key covariates, such as alcohol consumption, could shape the prevalence of different microbiota communities in the population. Finally, our analyses indicated that there is a relatively canalised pathway leading to the deterioration of vaginal microbiota communities, whereas the paths to recovery can be highly individualised among women. In addition to providing one of the first insights into vaginal microbiota dynamics over a year, our study showcases a novel application of a hierarchical Bayesian Markov model to clinical cohort data with many covariates. Our findings pave the way for an improved mechanistic understanding of microbial dynamics in the vaginal environment and the development of novel preventative and therapeutic strategies to improve vaginal health.

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影响年轻成年女性阴道微生物群长期群落动态的因素。
众所周知,阴道微生物群会影响妇女的健康。然而,持续数月的高分辨率随访研究却明显不足,而这需要对长期动态以及与人口和行为协变量的关系进行调查。在此,我们对 125 名妇女进行了高分辨率纵向队列研究,随访时间中位数为 8.6 个月,每名妇女采集的样本中位数为 11 个。通过使用分层贝叶斯马尔可夫模型,我们描述了阴道微生物群落的持续和过渡模式,同时估算了 16 个协变量的影响,并量化了妇女的个体差异。我们发现,"最优"(群落状态类型(CST)I、II 和 V)和 "次优"(CST III)群落随着时间的推移比 "非最优"(CST IV)群落更加稳定。此外,我们还发现一些协变量--最明显的是酒精消耗量--会影响从一种 CST 转向另一种 CST 的概率。我们进行了反事实模拟,以证实饮酒量等关键协变量的改变会影响不同微生物群落在人群中的流行程度。最后,我们的分析表明,导致阴道微生物群落恶化有一个相对固定的途径,而女性恢复的途径则高度个性化。我们的研究不仅首次揭示了一年内阴道微生物群的动态变化,还展示了将分层贝叶斯马尔可夫模型应用于具有多种协变量的临床队列数据的新方法。我们的研究结果为更好地从机理上理解阴道环境中的微生物动态以及开发新的预防和治疗策略以改善阴道健康铺平了道路。
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