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迈向与疾病相关的肠道微生物失调的共同特征:阿克曼氏菌黏蛋白的关键作用。

Towards a disease-associated common trait of gut microbiota dysbiosis: The pivotal role of Akkermansia muciniphila.

机构信息

UOC Medicina Interna e Gastroenterologia, Area Medicina Interna, Gastroenterologia ed Oncologia Medica, Dipartimento di Scienze Gastroenterologiche, Endocrino-Metaboliche e Nefro-Urologiche, Fondazione Policlinico Universitario A. Gemelli IRCCS, Largo Gemelli, 8, 00168 Rome, Italy; Department of Medicine and Ageing Sciences, "G. d'Annunzio" University of Chieti-Pescara, Chieti, Italy; Center for Advanced Studies and Technology (CAST), "G. d'Annunzio" University of Chieti-Pescara, Chieti, Italy.

Unità di Microbioma Umano, Ospedale Pediatrico "Bambino Gesù", IRCCS, Rome, Italy.

出版信息

Dig Liver Dis. 2020 Sep;52(9):1002-1010. doi: 10.1016/j.dld.2020.05.020. Epub 2020 Jun 20.

Abstract

BACKGROUND

Gut microbiota exerts a crucial role in gastrointestinal (GI) and extra-intestinal (EI) disorders. In this context, Akkermansia muciniphila is pivotal for the maintenance of host health and has been correlated with several disorders.

AIM

To explore the potential role of A. muciniphila as common dysbiotic marker linked to the disease status.

METHODS

A cohort of patients affected by GI and EI disorders was enrolled and compared to healthy controls (CTRLs). A targeted-metagenomics approach combined to unsupervised cluster and machine learning (ML) analyses provided microbiota signatures.

RESULTS

Microbiota composition was associated to disease phenotype, therapies, diet and anthropometric features, identifying phenotype and therapies as the most impacting variables on microbiota ecology. Unsupervised cluster analyses identified one cluster composed by the majority of patients. DESeq2 algorithm identified ten microbial discriminatory features of patients and CTRLs clusters. Among these microbes, Akkermansia muciniphila resulted the discriminating ML node between patients and CTRLs, independently of specific GI/EI disease or confounding effects. A. muciniphila decrease represented a transversal signature of gut microbiota alteration, showing also an inverse correlation with α-diversity.

CONCLUSION

Overall, A. muciniphila decline may have a crucial role in affecting microbial ecology and in discriminating patients from healthy subjects. Its grading may be considered as a gut dysbiosis feature associated to disease-related microbiota profile.

摘要

背景

肠道微生物群在胃肠道(GI)和肠外(EI)疾病中发挥着关键作用。在这种情况下,黏蛋白阿克曼菌对于维持宿主健康至关重要,并且与多种疾病有关。

目的

探索黏蛋白阿克曼菌作为与疾病状态相关的常见共生失调标志物的潜在作用。

方法

招募了一组患有 GI 和 EI 疾病的患者,并将其与健康对照组(CTRLs)进行比较。靶向宏基因组学方法结合无监督聚类和机器学习(ML)分析提供了微生物组特征。

结果

微生物群落组成与疾病表型、治疗、饮食和人体测量特征相关,确定表型和治疗是对微生物群落生态影响最大的变量。无监督聚类分析确定了由大多数患者组成的一个聚类。DESeq2 算法鉴定了患者和 CTRLs 聚类中十个具有区分性的微生物特征。在这些微生物中,黏蛋白阿克曼菌是区分患者和 CTRLs 的 ML 节点,独立于特定的 GI/EI 疾病或混杂效应。黏蛋白阿克曼菌的减少代表了肠道微生物群改变的横向特征,也与α多样性呈负相关。

结论

总之,黏蛋白阿克曼菌的减少可能在影响微生物群落和区分患者与健康受试者方面发挥着关键作用。其分级可被视为与疾病相关的微生物组特征相关的肠道菌群失调特征。

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