Multi-omics of the gut microbial ecosystem in inflammatory bowel diseases

被引：1996

作者：

Lloyd-Price, Jason ^{[1
,2
]}

Arze, Cesar ^{[2
]}

Ananthakrishnan, Ashwin N. ^{[3
]}

Schirmer, Melanie ^{[1
,3
]}

Avila-Pacheco, Julian ^{[4
]}

Poon, Tiffany W. ^{[1
]}

Andrews, Elizabeth ^{[3
]}

Ajami, Nadim J. ^{[5
]}

Bonham, Kevin S. ^{[1
,2
]}

Brislawn, Colin J. ^{[6
]}

Casero, David ^{[7
]}

Courtney, Holly ^{[3
]}

Gonzalez, Antonio ^{[8
]}

Graeber, Thomas G. ^{[9
]}

Hall, A. Brantley ^{[1
]}

Lake, Kathleen ^{[10
]}

Landers, Carol J. ^{[11
]}

Mallick, Himel ^{[1
,2
]}

Plichta, Damian R. ^{[1
]}

Prasad, Mahadev ^{[12
]}

Rahnavard, Gholamali ^{[1
,2
]}

Sauk, Jenny ^{[13
]}

Shungin, Dmitry ^{[1
,14
]}

Vazquez-Baeza, Yoshiki ^{[15
,16
]}

White, Richard A., III ^{[6
]}

Braun, Jonathan ^{[7
]}

Denson, Lee A. ^{[10
,17
]}

Jansson, Janet K. ^{[6
]}

Knight, Rob ^{[8
,16
,18
]}

Kugathasan, Subra ^{[12
]}

McGovern, Dermot P. B. ^{[11
]}

Petrosino, Joseph F. ^{[5
]}

Stappenbeck, Thaddeus S. ^{[19
]}

Winter, Harland S. ^{[20
,21
]}

Clish, Clary B. ^{[4
]}

Franzosa, Eric A. ^{[2
]}

Vlamakis, Hera ^{[1
]}

Xavier, Ramnik J. ^{[1
,3
,22
]}

Huttenhower, Curtis ^{[1
,2
]}

Bishai, Jason ^{[1
]}

Bullock, Kevin ^{[4
]}

Deik, Amy ^{[4
]}

Dennis, Courtney ^{[4
]}

Kaplan, Jess L. ^{[20
]}

Khalili, Hamed ^{[3
]}

McIver, Lauren J. ^{[2
]}

Moran, Christopher J. ^{[20
]}

Nguyen, Long ^{[3
]}

Pierce, Kerry A. ^{[4
]}

Schwager, Randall ^{[2
]}

机构：

[1] Broad Inst MIT & Harvard, Infect Dis & Microbiome Program, Cambridge, MA 02142 USA

[2] Harvard TH Chan Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA

[3] Massachusetts Gen Hosp, Gastroenterol, Boston, MA 02114 USA

[4] Broad Inst MIT & Harvard, Metabol Platform, Cambridge, MA 02142 USA

[5] Baylor Coll Med, Mol Virol & Microbiol, Houston, TX 77030 USA

[6] Pacific Northwest Natl Lab, Earth & Biol Sci Directorate, Richland, WA 99352 USA

[7] Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol & Lab Med, Los Angeles, CA 90095 USA

[8] Univ Calif San Diego, Dept Pediat, La Jolla, CA 92093 USA

[9] Univ Calif Los Angeles, Mol & Med Pharmacol, Los Angeles, CA USA

[10] Cincinnati Childrens Hosp Med Ctr, Dept Pediat, Cincinnati, OH 45229 USA

[11] Cedars Sinai Med Ctr, F Widjaja Fdn Inflammatory Bowel & Immunobiol Res, Los Angeles, CA 90048 USA

[12] Emory Univ, Dept Pediat, Atlanta, GA 30322 USA

[13] Univ Calif Los Angeles, Vatche & Tamar Manoukian Div Digest Dis, Los Angeles, CA USA

[14] Umea Univ, Dept Odontol, Umea, Sweden

[15] Univ Calif San Diego, Jacobs Sch Engn, La Jolla, CA 92093 USA

[16] Univ Calif San Diego, Ctr Microbiome Innovat, La Jolla, CA 92093 USA

[17] Univ Cincinnati, Coll Med, Dept Pediat, Cincinnati, OH USA

[18] Univ Calif San Diego, Dept Comp Sci & Engn, La Jolla, CA 92093 USA

[19] Washington Univ, Dept Pathol & Immunol, St Louis, MO 63110 USA

[20] MassGen Hosp Children, Dept Pediat, Boston, MA USA

[21] Harvard Med Sch, Dept Pediat, Boston, MA 02115 USA

[22] MIT, Ctr Microbiome Informat & Therapeut, 77 Massachusetts Ave, Cambridge, MA 02139 USA

来源：

NATURE | 2019年 / 569卷 / 7758期

基金：

美国国家科学基金会; 瑞典研究理事会; 美国国家卫生研究院;

关键词：

DIFFERENTIAL EXPRESSION ANALYSIS; CROHNS-DISEASE; GENE-EXPRESSION; COLLECTION METHODS; FECAL SAMPLES; DYNAMICS; ACID; ASSOCIATION; COMPLEMENT; DATABASE;

D O I：

10.1038/s41586-019-1237-9

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：

Inflammatory bowel diseases, which include Crohn's disease and ulcerative colitis, affect several million individuals worldwide. Crohn's disease and ulcerative colitis are complex diseases that are heterogeneous at the clinical, immunological, molecular, genetic, and microbial levels. Individual contributing factors have been the focus of extensive research. As part of the Integrative Human Microbiome Project (HMP2 or iHMP), we followed 132 subjects for one year each to generate integrated longitudinal molecular profiles of host and microbial activity during disease (up to 24 time points each; in total 2,965 stool, biopsy, and blood specimens). Here we present the results, which provide a comprehensive view of functional dysbiosis in the gut microbiome during inflammatory bowel disease activity. We demonstrate a characteristic increase in facultative anaerobes at the expense of obligate anaerobes, as well as molecular disruptions in microbial transcription (for example, among clostridia), metabolite pools (acylcarnitines, bile acids, and short-chain fatty acids), and levels of antibodies in host serum. Periods of disease activity were also marked by increases in temporal variability, with characteristic taxonomic, functional, and biochemical shifts. Finally, integrative analysis identified microbial, biochemical, and host factors central to this dysregulation. The study's infrastructure resources, results, and data, which are available through the Inflammatory Bowel Disease Multi'omics Database (http://ibdmdb.org), provide the most comprehensive description to date of host and microbial activities in inflammatory bowel diseases.

引用

页码：655 / +

页数：26

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