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更多阳性还是更多阴性?病毒组的宏基因组分析揭示了病毒组在与人类疾病相关的肠道微生物组中的作用。

More Positive or More Negative? Metagenomic Analysis Reveals Roles of Virome in Human Disease-Related Gut Microbiome.

机构信息

Peking University-Tsinghua University-National Institute of Biological Sciences (PTN) Joint Ph.D. Program, School of Life Sciences, Peking University, Beijing, China.

Department of Biomedical Engineering, College of Future Technology, Peking University, Beijing, China.

出版信息

Front Cell Infect Microbiol. 2022 Apr 12;12:846063. doi: 10.3389/fcimb.2022.846063. eCollection 2022.

Abstract

Viruses are increasingly viewed as vital components of the human gut microbiota, while their roles in health and diseases remain incompletely understood. Here, we first sequenced and analyzed the 37 metagenomic and 18 host metabolomic samples related to irritable bowel syndrome (IBS) and found that some shifted viruses between IBS and controls covaried with shifted bacteria and metabolites. Especially, phages that infect beneficial lactic acid bacteria depleted in IBS covaried with their hosts. We also retrieved public whole-genome metagenomic datasets of another four diseases (type 2 diabetes, Crohn's disease, colorectal cancer, and liver cirrhosis), totaling 438 samples including IBS, and performed uniform analysis of the gut viruses in diseases. By constructing disease-specific co-occurrence networks, we found viruses actively interacting with bacteria, negatively correlated with possible dysbiosis-related and inflammation-mediating bacteria, increasing the connectivity between bacteria modules, and contributing to the robustness of the networks. Functional enrichment analysis showed that phages interact with bacteria through predation or expressing genes involved in the transporter and secretion system, metabolic enzymes, . We further built a viral database to facilitate systematic functional classification and explored the functions of viral genes on interacting with bacteria. Our analyses provided a systematic view of the gut virome in the disease-related microbial community and suggested possible positive roles of viruses concerning gut health.

摘要

病毒被越来越多地视为人类肠道微生物群的重要组成部分,但其在健康和疾病中的作用仍不完全清楚。在这里,我们首先对与肠易激综合征(IBS)相关的 37 个宏基因组和 18 个宿主代谢组样本进行了测序和分析,发现 IBS 组和对照组之间一些发生变化的病毒与发生变化的细菌和代谢物有关。特别是,感染有益的乳杆菌且在 IBS 中减少的噬菌体与其宿主发生共变。我们还检索了另外四种疾病(2 型糖尿病、克罗恩病、结直肠癌和肝硬化)的公共全基因组宏基因组数据集,包括 IBS 在内的 438 个样本,并对疾病中的肠道病毒进行了统一分析。通过构建特定疾病的共现网络,我们发现病毒与细菌积极相互作用,与可能与菌群失调和炎症调节相关的细菌呈负相关,增加了细菌模块之间的连接性,并有助于网络的稳健性。功能富集分析表明,噬菌体通过捕食或表达与转运体和分泌系统、代谢酶相关的基因与细菌相互作用。我们进一步构建了一个病毒数据库,以方便系统的功能分类,并探索了病毒基因与细菌相互作用的功能。我们的分析提供了疾病相关微生物群落中肠道病毒组的系统视图,并表明病毒在肠道健康方面可能发挥积极作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4661/9040671/573cdb5c9eeb/fcimb-12-846063-g001.jpg

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