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对36项肠道微生物组研究的人群规模分析揭示了常见疾病的普遍物种特征

A population-scale analysis of 36 gut microbiome studies reveals universal species signatures for common diseases

Nature 等信源发布 2024-10-01 09:02

可切换为仅中文


AbstractThe gut microbiome has been implicated in various human diseases, though findings across studies have shown considerable variability. In this study, we reanalyzed 6314 publicly available fecal metagenomes from 36 case-control studies on different diseases to investigate microbial diversity and disease-shared signatures.

摘要肠道微生物组与各种人类疾病有关,尽管各项研究的结果显示出相当大的差异。在这项研究中,我们重新分析了来自36个不同疾病病例对照研究的6314个公开可用的粪便宏基因组,以调查微生物多样性和疾病共享特征。

Using a unified analysis pipeline, we observed reduced microbial diversity in many diseases, while some exhibited increased diversity. Significant alterations in microbial communities were detected across most diseases. A meta-analysis identified 277 disease-associated gut species, including numerous opportunistic pathogens enriched in patients and a depletion of beneficial microbes.

使用统一的分析流程,我们观察到许多疾病的微生物多样性降低,而一些疾病的多样性增加。在大多数疾病中检测到微生物群落的显着变化。一项荟萃分析确定了277种与疾病相关的肠道物种,包括许多富含患者的机会性病原体和有益微生物的消耗。

A random forest classifier based on these signatures achieved high accuracy in distinguishing diseased individuals from controls (AUC = 0.776) and high-risk patients from controls (AUC = 0.825), and it also performed well in external cohorts. These results offer insights into the gut microbiome’s role in common diseases in the Chinese population and will guide personalized disease management strategies..

基于这些特征的随机森林分类器在区分患病个体与对照(AUC=0.776)和高危患者与对照(AUC=0.825)方面取得了很高的准确性,并且在外部队列中也表现良好。这些结果提供了对肠道微生物组在中国人群常见疾病中的作用的见解,并将指导个性化疾病管理策略。。

IntroductionThe gut microbiota is currently considered a key factor contributing to the regulation of host health1,2. Generally, the overall structure of the gut microbiota is relatively stable despite acute perturbations because of its plasticity, which allows it to quickly return to its initial composition3.

引言肠道微生物群目前被认为是调节宿主健康的关键因素1,2。一般来说,肠道微生物群的整体结构相对稳定,尽管由于其可塑性而受到严重干扰,这使得它能够迅速恢复到其初始组成3。

However, when hosts are continuously exposed to various pollutants, stresses and diseases, the composition of the gut microbiota might change (dysbiosis), promoting the selection of more virulent microorganisms and potentially harming host health3. With the advancement of amplification-based and whole-metagenomic sequencing technologies, gut microbiota dysbiosis has been widely reported in many common diseases, including autoimmune disorders4,5,6, cardiometabolic conditions7,8, infectious diseases9, psychiatric disorders10,11, and cancers12,13,14.

然而,当宿主持续暴露于各种污染物,压力和疾病时,肠道微生物群的组成可能会改变(生态失调),促进选择更具毒性的微生物,并可能损害宿主健康3。随着基于扩增和全宏基因组测序技术的进步,肠道微生物群生态失调已在许多常见疾病中得到广泛报道,包括自身免疫性疾病4,5,6,心脏代谢状况7,8,传染病9,精神疾病10,11和癌症12,13,14。

The altered microbiome likely plays a crucial role in these diseases. The varying microbial changes across different diseases emphasize the diverse roles of the microbiota in health and disease states15,16,17,18. However, due to the lack of unified reference databases, the low accuracy of bacterial species annotation and quantification in high-throughput sequencing datasets, and the highly variable experimental and analytical methods used, the signatures of the gut microbiota in different disease states are often incomparable.

改变的微生物组可能在这些疾病中起着至关重要的作用。不同疾病的不同微生物变化强调了微生物群在健康和疾病状态中的不同作用15,16,17,18。然而,由于缺乏统一的参考数据库,高通量测序数据集中细菌物种注释和定量的准确性低,以及使用的高度可变的实验和分析方法,不同疾病状态下肠道微生物群的特征通常是不可比的。

Additionally, the precise cause of microbial dysfunction in these diseases is not completely understood. Therefore, uniform methods to characterize the gut microbiota in multiple diseases, especially using publicly available datasets, are necessary to identify the overall pattern of disease-associated microbiota shifts.Meta-analysis, which combines data from multiple studies, can help avoid biases .

此外,这些疾病中微生物功能障碍的确切原因尚不完全清楚。因此,有必要采用统一的方法来表征多种疾病中的肠道微生物群,特别是使用公开可用的数据集,以确定疾病相关微生物群变化的总体模式。荟萃分析结合了多项研究的数据,可以帮助避免偏见。

Data availability

数据可用性

The metadata, gut microbial profiles of all analyzed samples, and statistical scripts are available on the GitHub website (https://github.com/yexianingyue/GM_common_diseases). The authors declare that all other data supporting the findings of the study are available in the paper and supplementary materials or from the corresponding authors upon request..

所有分析样品的元数据、肠道微生物谱和统计脚本都可以在GitHub网站上找到(https://github.com/yexianingyue/GM_common_diseases)。作者声明,支持研究结果的所有其他数据均可在论文和补充材料中获得,或应要求从通讯作者处获得。。

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Download referencesAcknowledgementsThis work was supported by grants from the National Natural Science Foundation of China (81902037, 81503455, and 82370563), and Beijing University of Chinese Medicine (NO.5050071720001 and NO.2180072120049).Author informationAuthor notesThese authors contributed equally: Wen Sun, Yue Zhang, Ruochun Guo, Shanshan Sha, Changming Chen.Authors and AffiliationsCentre for Translational Medicine, Shenzhen Bao’an Chinese Medicine Hospital, Guangzhou University of Chinese Medicine, Shenzhen, 518000, ChinaWen SunKey Laboratory of Health Cultivation of the Ministry of Education, Beijing University of Chinese Medicine, Beijing, 100029, ChinaWen SunSchool of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, 100700, ChinaWen Sun & Jie MaPuensum Genetech Institute, Wuhan, 430076, ChinaYue Zhang, Ruochun Guo, Jinxin Meng, Qingbo Lv & Shenghui LiDepartment of Microbiology, Department of Biochemistry and Molecular Biology, College of Basic Medical Sciences, Dalian Medical University, Dalian, 116044, ChinaShanshan Sha, Hayan Ullah, Lin Cheng, Shao Fan, Rui Li & Qiulong YanDepartment of Rheumatology and Immunology, The Second Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, Guiyang, 550001, ChinaChangming ChenDepartment of Traditional Chinese Medicine, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, ChinaYan ZhangDepartment of Acupuncture and Moxibustion, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, 100010, ChinaWei YouDepartment Orthopedics, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, 100700, ChinaXiaohong MuSchool of Chemistry, Chemical Engineering and Life Science, Hubei Key Laboratory of .

下载参考文献致谢这项工作得到了国家自然科学基金(819020378150345和82370563)和北京中医药大学(NO.5050071720001和NO.2180072120049)的资助。作者信息作者注意到这些作者做出了同样的贡献:孙文,张悦,郭若春,沙珊珊,陈昌明。作者和附属机构广州中医药大学深圳宝安中医医院转化医学中心,深圳,518000,北京中医药大学教育部健康培育国家重点实验室,北京,100029,北京中医药大学中医学院,北京,100700,武汉,430076,张跃跃,郭若春,孟金新,吕庆波和盛辉,大连医科大学基础医学院生物化学与分子生物学系,微生物学系,大连,116044,中国上海,海山贵州中医药大学第二附属医院风湿免疫科,贵阳,550001,中国陈昌明北京友谊医院中医科,首都医科大学,北京,100050,中国张燕首都医科大学北京中医院针灸科,北京,100010,中国北京中医药大学东直门医院骨科,北京,100700,中国小红化学化工与生命科学学院,湖北省重点实验室。

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PubMed Google ScholarContributionsS.L., Q.Y., Yue Z., R.G., X.M., and W.S. contributed to the conception and design of the study. Yue Z., L.C., S.F., and R.L. downloaded and processed the publicly available datasets. Yue Z., Yan Z., S.L., R.G., S.S., J.M., H.U. and Q.L. performed the bioinformatics analyses.

PubMed谷歌学术贡献。五十、 ,Q.Y.,Yue Z.,R.G.,X.M。和W.S.为研究的概念和设计做出了贡献。Yue Z.,L.C.,S.F。和R.L.下载并处理了公开可用的数据集。Yue Z.,Yan Z.,S.L.,R.G.,S.S.,J.M.,H.U.和Q.L.进行了生物信息学分析。

S.L., S.S., and C.C. wrote the manuscript. S.L. and W.S. helped to draft the manuscript. J.M. and W.Y. contributed meaningful discussions. All authors were involved in preparing the manuscript and contributed to manuscript revision, reading, and approving the submitted version.Corresponding authorsCorrespondence to.

S、 L.,S.S。和C.C.撰写了手稿。S、 L.和W.S.帮助起草了手稿。J、 M.和W.Y.进行了有意义的讨论。所有作者都参与了稿件的准备,并为稿件的修订,阅读和批准提交的版本做出了贡献。通讯作者通讯。

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Reprints and permissionsAbout this articleCite this articleSun, W., Zhang, Y., Guo, R. et al. A population-scale analysis of 36 gut microbiome studies reveals universal species signatures for common diseases.

转载和许可本文引用本文Sun,W.,Zhang,Y.,Guo,R。等人。对36个肠道微生物组研究的人口规模分析揭示了常见疾病的普遍物种特征。

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