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跨队列微生物组全研究揭示,高血压患者的肠道细菌群落存在一致变化,但肠道真菌群落无此变化。

Cross-cohort microbiome-wide study reveals consistent alterations in the gut bacteriome, but not the gut mycobiome, in patients with hypertension.

作者信息

Gao Yidan, Wang Dangrang, Lu Tong, Liu Kan, Li Shenghui, Kang Jian, Sha Shanshan, Xing Guorui, Cheng Lin, Fan Shao, Yang Wei, Yan Qiulong, Ding Yanchun, Xu Dafeng

机构信息

Cardiology II Department, The Second Hospital of Dalian Medical University, Dalian, China.

Health Management Center, The Second Hospital of Dalian Medical University, Dalian, China.

出版信息

mSystems. 2025 Aug 15:e0065725. doi: 10.1128/msystems.00657-25.

DOI:10.1128/msystems.00657-25
PMID:40815468
Abstract

UNLABELLED

Hypertension, one of the most prevalent cardiovascular diseases, has been linked to the gut microbiota. However, there is a lack of well-defined, cross-population validated gut microbial signatures associated with hypertension, particularly at both the bacterial and fungal levels. To address this gap, we conducted a metagenome-wide analysis of fecal samples from 159 hypertensive patients and 101 healthy controls, using two publicly available data sets from the Beijing and Dalian regions. Our results showed that hypertensive patients exhibit a significant reduction in gut bacterial diversity, accompanied by substantial alterations in bacterial composition. A total of 61 bacterial species were identified with significantly different relative abundance between patients and controls across both regions (combined < 0.05, = 0.25). Hypertension-enriched species included (, ) and sp. AT4, while , , and sp. AM49 4BH were significantly decreased in hypertensive patients. In contrast, no significant differences were observed in gut fungal diversity between hypertensive patients and healthy controls, and only minor differences in fungal composition were noted. Specifically, six fungal species were identified as potentially significant in the combined data set ( < 0.05, = 0.73), but they only c231 meet the same consistency across the two cohorts as the bacterial signatures. Furthermore, we developed classification models using gut bacterial and fungal signatures to distinguish hypertension patients from healthy controls. The bacterium-based models achieved area under the curves (AUCs) greater than 0.70 in cross-cohort classification and validation, while the fungus-based models only achieved AUCs between 0.55 and 0.57. In summary, our study identifies cross-cohort gut bacterial and fungal signatures associated with hypertension, suggesting that the gut bacteriome may serve as a more reliable target for hypertension intervention compared to the gut mycobiome.

IMPORTANCE

Hypertension (HTN) represents a global health burden affecting billions of individuals worldwide; however, the relationship between HTN and gut microbial ecosystems remains inadequately characterized. This study presents the first cross-cohort microbiome analysis revealing significant alterations in the gut bacteriome of HTN patients, with limited changes observed in the mycobiome. These findings highlight the critical role of the gut bacteriome in the pathogenesis of HTN and provide new microbial biomarkers for early diagnosis. Furthermore, the identification of bacterial species establishes a foundation for future intervention approaches, enhancing the applicability of microbiome research in cardiovascular health and opening new avenues for related studies in this field.

摘要

未标记

高血压是最常见的心血管疾病之一,与肠道微生物群有关。然而,缺乏明确的、经过跨人群验证的与高血压相关的肠道微生物特征,特别是在细菌和真菌水平上。为了填补这一空白,我们使用来自北京和大连地区的两个公开数据集,对159名高血压患者和101名健康对照的粪便样本进行了宏基因组分析。我们的结果表明,高血压患者的肠道细菌多样性显著降低,同时细菌组成也发生了实质性改变。在两个地区的患者和对照之间,共鉴定出61种细菌的相对丰度存在显著差异(合并P<0.05,FDR = 0.25)。高血压富集的物种包括(,)和sp. AT4,而,和sp. AM49 4BH在高血压患者中显著减少。相比之下,高血压患者和健康对照之间的肠道真菌多样性没有观察到显著差异,仅在真菌组成上有微小差异。具体而言,在合并数据集中鉴定出6种真菌物种具有潜在显著性(P<0.05,FDR = 0.73),但它们在两个队列中的一致性仅与细菌特征相同。此外,我们使用肠道细菌和真菌特征开发了分类模型,以区分高血压患者和健康对照。基于细菌的模型在跨队列分类和验证中获得的曲线下面积(AUC)大于0.70,而基于真菌的模型仅获得0.55至0.57之间的AUC。总之,我们的研究确定了与高血压相关的跨队列肠道细菌和真菌特征,表明与肠道真菌群相比,肠道细菌群可能是高血压干预更可靠的靶点。

重要性

高血压(HTN)是一项影响全球数十亿人的全球健康负担;然而,HTN与肠道微生物生态系统之间的关系仍未得到充分表征。本研究首次进行了跨队列微生物组分析,揭示了HTN患者肠道细菌群的显著改变,而真菌群的变化有限。这些发现突出了肠道细菌群在HTN发病机制中的关键作用,并为早期诊断提供了新的微生物生物标志物。此外,细菌物种的鉴定为未来的干预方法奠定了基础,增强了微生物组研究在心血管健康中的适用性,并为该领域的相关研究开辟了新途径。

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