Microbiota-based markers predictive of development of Clostridioides difficile infection

被引：53

作者：

Berkell, Matilda ^{[1
]}

Mysara, Mohamed ^{[1
,2
]}

Xavier, Basil Britto ^{[1
]}

van Werkhoven, Cornelis H. ^{[3
]}

Monsieurs, Pieter ^{[2
,9
]}

Lammens, Christine ^{[1
]}

Ducher, Annie ^{[4
]}

Vehreschild, Maria J. G. T. ^{[5
,6
,7
]}

Goossens, Herman ^{[1
]}

de Gunzburg, Jean ^{[4
]}

Bonten, Marc J. M. ^{[3
,8
]}

Malhotra-Kumar, Surbhi ^{[1
]}

Engbers, Annemarie ^{[3
]}

de Regt, Marieke ^{[10
]}

Biehl, Lena M. ^{[5
]}

Cornely, Oliver A. ^{[5
]}

Jazmati, Nathalie ^{[11
]}

Bouverne, Marie-Noelle ^{[4
]}

Sablier-Gallis, Frederique ^{[4
]}

Mentre, France ^{[12
,13
]}

Merle, Uta ^{[14
]}

Stallmach, Andreas ^{[15
]}

Rupp, Jan ^{[16
]}

Bogner, Johannes ^{[17
]}

Lubbert, Christoph ^{[18
]}

Silling, Gerda ^{[19
]}

Witzke, Oliver ^{[20
]}

Gikas, Achilleas ^{[21
]}

Maraki, Sofia ^{[21
]}

Daikos, George ^{[22
]}

Tsiodras, Sotirios ^{[23
]}

Skoutelis, Athanasios ^{[24
]}

Sambatakou, Helen ^{[25
]}

Pujol, Miguel ^{[26
]}

Dominguez-Luzon, M. Angeles ^{[26
]}

Aguado, Jose M. ^{[27
]}

Bouza, Emilio ^{[28
]}

Cobo, Javier ^{[29
]}

Rodriguez-Bano, Jesus ^{[30
]}

Almirante, Benito ^{[31
]}

Cisneros, Julian de la Torre ^{[32
]}

Florescu, Simin A. ^{[33
]}

Nica, Maria ^{[33
]}

Vata, Andrei ^{[34
]}

Hristea, Adriana ^{[35
]}

Lupse, Mihaela ^{[36
]}

Herghea, Delia ^{[37
]}

Postil, Deborah ^{[38
]}

Barraud, Olivier ^{[38
]}

Molina, Jean-Michel ^{[39
]}

机构：

[1] Univ Antwerp, Vaccine & Infect Dis Inst, Lab Med Microbiol, Antwerp, Belgium

[2] Belgian Nucl Res Ctr, Interdisciplinary Biosci, Microbiol Unit, SCK CEN, Mol, Belgium

[3] Univ Utrecht, Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands

[4] Da Volterra, Paris, France

[5] Univ Cologne, Ctr Integrated Oncol Aachen Bonn Cologne Duesseld, Dept Internal Med, Cologne, Germany

[6] German Ctr Infect Res DZIF, Partner Site Bonn Cologne, Cologne, Germany

[7] Goethe Univ Frankfurt, Univ Hosp Frankfurt, Dept Internal Med, Frankfurt, Germany

[8] Univ Utrecht, Univ Med Ctr Utrecht, Dept Med Microbiol, Utrecht, Netherlands

[9] Inst Trop Med, Dept Biomed Sci, Antwerp, Belgium

[10] Univ Med Ctr Utrecht, Dept Internal Med, Utrecht, Netherlands

[11] Univ Cologne, Inst Med Microbiol Immunol & Hyg, Cologne, Germany

[12] INSERM, Paris, France

[13] Paris Diderot Univ, IAME, Paris, France

[14] Univ Klinikum Heidelberg, Heidelberg, Germany

[15] Univ Klinikum Jena, Jena, Germany

[16] Univ Klinikum Schleswig Holstein, Lubeck, Germany

[17] Klinikum Univ Munchen, Munich, Germany

[18] Univ Klinikum Leipzig, Leipzig, Germany

[19] Univ Klinikum Aachen, Aachen, Germany

[20] Univ Klinikum Essen, Essen, Germany

[21] Univ Hosp Heraklion, Iraklion, Greece

[22] Laikon Gen Hosp, Athens, Greece

[23] Univ Gen Hosp ATTIKON, Athens, Greece

[24] Evangelismos Gen Hosp, Athens, Greece

[25] Ippokratio Hosp, Athens, Greece

[26] Univ Barcelona, Hosp Univ Bellvitge, IDIBELL, Barcelona, Spain

[27] Hosp Univ 12 Octubre, Madrid, Spain

[28] Hosp Univ Gregorio Maranon, Madrid, Spain

[29] Hosp Univ Ramon y Cajal, Madrid, Spain

[30] Hosp Univ Virgen Macarena, Seville, Spain

[31] Hosp Univ Vali dHebron, Barcelona, Spain

[32] UCO, IMBIC, Hosp Univ Reina Sofia, Cordoba, Spain

[33] Infect & Trop Dis Hosp Dr Victor Babes, Bucharest, Romania

[34] Clin Hosp Infect Dis Iasi, Iasi, Romania

[35] Natl Inst Infect Dis Matei Bals, Bucharest, Romania

[36] Cluj Napoca Infect Dis Clin Hosp, Cluj Napoca, Romania

[37] 0Ncol Inst Prof Dr I Chiricuta, Cluj Napoca, Romania

[38] Ctr Hosp Univ Dupuytren, Limoges, France

[39] Hop St Louis, Paris, France

[40] AP HP Beaujon, Paris, France

[41] Ctr Hosp Dept Vendee, La Roche Sur Yon, France

[42] CH Cornouaille, Quimper, France

[43] AP HP Bichat, Paris, France

[44] CHU Tours, Tours, Indre & Loire, France

[45] Hop Cochin, AP HP, Paris, France

来源：

NATURE COMMUNICATIONS | 2021年 / 12卷 / 01期

关键词：

INTESTINAL MICROBIOTA; GUT MICROBIOTA; SEQUENCE DATA; RISK; CLASSIFIER; IMPACTS; TAXA;

D O I：

10.1038/s41467-021-22302-0

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Antibiotic-induced modulation of the intestinal microbiota can lead to Clostridioides difficile infection (CDI), which is associated with considerable morbidity, mortality, and healthcare-costs globally. Therefore, identification of markers predictive of CDI could substantially contribute to guiding therapy and decreasing the infection burden. Here, we analyze the intestinal microbiota of hospitalized patients at increased CDI risk in a prospective, 90-day cohort-study before and after antibiotic treatment and at diarrhea onset. We show that patients developing CDI already exhibit significantly lower diversity before antibiotic treatment and a distinct microbiota enriched in Enterococcus and depleted of Ruminococcus, Blautia, Prevotella and Bifidobacterium compared to non-CDI patients. We find that antibiotic treatment-induced dysbiosis is class-specific with beta-lactams further increasing enterococcal abundance. Our findings, validated in an independent prospective patient cohort developing CDI, can be exploited to enrich for high-risk patients in prospective clinical trials, and to develop predictive microbiota-based diagnostics for management of patients at risk for CDI.Clostridioides difficile infection (CDI) is the most common cause of antibiotic-associated diarrhoea (AAD); however, markers predictive of CDI or AAD development are as yet lacking. Here, to identify markers predictive of CDI, the authors profile the intestinal microbiota of 945 hospitalised patients from 34 hospitals in 6 different European countries and show distinct microbiota enriched in Enterococcus and depleted of Ruminococcus, Blautia, Prevotella and Bifidobacterium compared to non-CDI patients.

引用

页数：14

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