Sự gia tăng của Prevotella copri trong ruột tương quan với sự nhạy cảm cao hơn đối với bệnh viêm khớp

eLife - Tập 2
Jose U. Scher1, Andrew Sczesnak2,3,4, Randy Longman5,3,4, Nicola Segata6,7, Carles Úbeda8,9, Craig M. Bielski7, Tim Rostron10, Vincenzo Cerundolo10, Eric G. Pamer9, Steven B. Abramson1, Curtis Huttenhower7, Dan R. Littman11,3,4
1Department of Medicine, New York University School of Medicine and Hospital for Joint Diseases, New York, United States;
2Graduate Program in Bioinformatics and Computational Biology, University of California, San Francisco, San Francisco, United States;
3Molecular Pathogenesis Program, The Kimmel Center for Biology and Medicine of the Skirball Institute, New York University School of Medicine, New York, United States
4School of Medicine, New York, United States;
5Jill Roberts IBD Center, Department of Medicine, Weill Cornell Medical College, New York, United States;
6Centre for Integrative Biology, University of Trento, Trento, Italy
7Department of Biostatistics, Harvard School of Public Health, Boston, United States;
8Centro Superior de Investigacion en Salud Publica, University of Valencia, Valencia, Spain;
9Immunology Program, Infectious Diseases Service, and The Lucille Castori Center for Microbes, Inflammation, and Cancer, Memorial Sloan-Kettering Cancer Center, New York, United States;
10Department of Medicine, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom;
11Howard Hughes Medical Institute, New York University School of Medicine, New York, United States

Tóm tắt

Viêm khớp dạng thấp (RA) là một bệnh tự miễn hệ thống phổ biến, do sự kết hợp của các yếu tố di truyền và môi trường gây ra. Các mô hình động vật gợi ý rằng vi khuẩn ruột có vai trò trong việc hỗ trợ phản ứng miễn dịch hệ thống cần thiết cho sự viêm khớp. Trong nghiên cứu này, chúng tôi thực hiện giải trình tự 16S trên 114 mẫu phân từ bệnh nhân viêm khớp dạng thấp và các đối chứng, và giải trình tự shotgun trên một tập hợp con gồm 44 mẫu như vậy. Chúng tôi xác định sự hiện diện của Prevotella copri có mối tương quan mạnh với bệnh ở những bệnh nhân viêm khớp dạng thấp mới khởi phát chưa được điều trị (NORA). Sự gia tăng trong sự phong phú của Prevotella tương quan với sự giảm bớt của Bacteroides và mất đi các vi sinh vật được cho là có lợi ở những đối tượng NORA. Chúng tôi cũng phát hiện ra các gen duy nhất của Prevotella có mối liên hệ với bệnh. Hơn nữa, việc thuộc địa hóa ở chuột cho thấy khả năng của P. copri chiếm ưu thế trong hệ vi sinh vật đường ruột và dẫn đến tăng độ nhạy cảm với viêm đại tràng do hóa chất được kích thích. Công trình này xác định một vai trò tiềm năng của P. copri trong sinh bệnh học của viêm khớp dạng thấp.

Từ khóa


Tài liệu tham khảo

Abdollahi-Roodsaz, 2008, Stimulation of TLR2 and TLR4 differentially skews the balance of T cells in a mouse model of arthritis, J Clin Invest, 118, 205, 10.1172/JCI32639

Abubucker, 2012, Metabolic reconstruction for metagenomic data and its application to the human microbiome, PLOS Comput Biol, 8, e1002358, 10.1371/journal.pcbi.1002358

Aletaha, 2010, 2010 rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative, Arthritis Rheum, 62, 2569, 10.1002/art.27584

Arumugam, 2011, Enterotypes of the human gut microbiome, Nature, 473, 174, 10.1038/nature09944

Atarashi, 2011, Induction of colonic regulatory T cells by indigenous Clostridium species, Science, 331, 337, 10.1126/science.1198469

Becker, 2006, High resolution colonoscopy in live mice, Nat Protoc, 1, 2900, 10.1038/nprot.2006.446

Deane, 2010, Preclinical rheumatoid arthritis: identification, evaluation, and future directions for investigation, Rheum Dis Clin North Am, 36, 213, 10.1016/j.rdc.2010.02.001

Diehl, 2013, Microbiota restricts trafficking of bacteria to mesenteric lymph nodes by CX(3)CR1(hi) cells, Nature, 494, 116, 10.1038/nature11809

du Montcel, 2005, New classification of HLA-DRB1 alleles supports the shared epitope hypothesis of rheumatoid arthritis susceptibility, Arthritis Rheum, 52, 1063, 10.1002/art.20989

Edgar, 2004, MUSCLE: multiple sequence alignment with high accuracy and high throughput, Nucleic Acids Res, 32, 1792, 10.1093/nar/gkh340

Edgar, 2010, Search and clustering orders of magnitude faster than BLAST, Bioinformatics, 26, 2460, 10.1093/bioinformatics/btq461

Elinav, 2011, NLRP6 inflammasome regulates colonic microbial ecology and risk for colitis, Cell, 145, 745, 10.1016/j.cell.2011.04.022

Faust, 2012, Microbial co-occurrence relationships in the human microbiome, PLOS Comput Biol, 8, e1002606, 10.1371/journal.pcbi.1002606

Frank, 2011, Disease phenotype and genotype are associated with shifts in intestinal-associated microbiota in inflammatory bowel diseases, Inflamm Bowel Dis, 17, 179, 10.1002/ibd.21339

Gomez, 2012, Loss of sex and age driven differences in the gut microbiome characterize arthritis-susceptible 0401 mice but not arthritis-resistant 0402 mice, PLOS ONE, 7, e36095, 10.1371/journal.pone.0036095

Gregersen, 1987, The shared epitope hypothesis. An approach to understanding the molecular genetics of susceptibility to rheumatoid arthritis, Arthritis Rheum, 30, 1205, 10.1002/art.1780301102

Haas, 2011, Chimeric 16S rRNA sequence formation and detection in Sanger and 454-pyrosequenced PCR amplicons, Genome Res, 21, 494, 10.1101/gr.112730.110

Hayashi, 2007, Prevotella copri sp. nov. and Prevotella stercorea sp. nov., isolated from human faeces, Int J Syst Evol Microbiol, 57, 941, 10.1099/ijs.0.64778-0

Human Microbiome Project Consortium, 2012, Structure, function and diversity of the healthy human microbiome, Nature, 486, 207, 10.1038/nature11234

Huse, 2010, Ironing out the wrinkles in the rare biosphere through improved OTU clustering, Environ Microbiol, 12, 1889, 10.1111/j.1462-2920.2010.02193.x

Ivanov, 2009, Induction of intestinal Th17 cells by segmented filamentous bacteria, Cell, 139, 485, 10.1016/j.cell.2009.09.033

Kanehisa, 2000, KEGG: kyoto encyclopedia of genes and genomes, Nucleic Acids Res, 28, 27, 10.1093/nar/28.1.27

Koeth, 2013, Intestinal microbiota metabolism of l-carnitine, a nutrient in red meat, promotes atherosclerosis, Nat Med, 19, 576, 10.1038/nm.3145

Littman, 2011, Role of the commensal microbiota in normal and pathogenic host immune responses, Cell Host Microbe, 10, 311, 10.1016/j.chom.2011.10.004

Luo, 2012, SOAPdenovo2: an empirically improved memory-efficient short-read de novo assembler, Gigascience, 1, 18, 10.1186/2047-217X-1-18

Maurice, 1999, Expression of the thioredoxin-thioredoxin reductase system in the inflamed joints of patients with rheumatoid arthritis, Arthritis Rheum, 42, 2430, 10.1002/1529-0131(199911)42:11<2430::AID-ANR22>3.0.CO;2-6

McInnes, 2011, The pathogenesis of rheumatoid arthritis, N Engl J Med, 365, 2205, 10.1056/NEJMra1004965

Morgan, 2012, Dysfunction of the intestinal microbiome in inflammatory bowel disease and treatment, Genome Biol, 13, R79, 10.1186/gb-2012-13-9-r79

Pop M. 2011. HMP Whole-Metagenome Assembly. http://www.hmpdacc.org/doc/HMP_Assembly_SOP.pdf.

Price, 2010, FastTree 2–approximately maximum-likelihood trees for large alignments, PLOS ONE, 5, e9490, 10.1371/journal.pone.0009490

Pruesse, 2007, SILVA: a comprehensive online resource for quality checked and aligned ribosomal RNA sequence data compatible with ARB, Nucleic Acids Res, 35, 7188, 10.1093/nar/gkm864

Qin, 2010, A human gut microbial gene catalogue established by metagenomic sequencing, Nature, 464, 59, 10.1038/nature08821

Qin, 2012, A metagenome-wide association study of gut microbiota in type 2 diabetes, Nature, 490, 55, 10.1038/nature11450

Rath, 1996, Normal luminal bacteria, especially Bacteroides species, mediate chronic colitis, gastritis, and arthritis in HLA-B27/human beta2 microglobulin transgenic rats, J Clin Invest, 98, 945, 10.1172/JCI118878

Round, 2011, The Toll-like receptor 2 pathway establishes colonization by a commensal of the human microbiota, Science, 332, 974, 10.1126/science.1206095

Scher, 2011, The microbiome and rheumatoid arthritis, Nat Rev Rheumatol, 7, 569, 10.1038/nrrheum.2011.121

Scher, 2012, Periodontal disease and the oral microbiota in new-onset rheumatoid arthritis, Arthritis Rheum, 64, 3083, 10.1002/art.34539

Schloissnig, 2013, Genomic variation landscape of the human gut microbiome, Nature, 493, 45, 10.1038/nature11711

Schloss, 2009, Introducing mothur: open-source, platform-independent, community-supported software for describing and comparing microbial communities, Appl Environ Microbiol, 75, 7537, 10.1128/AEM.01541-09

Sczesnak, 2011, The genome of Th17 cell-inducing segmented filamentous bacteria reveals extensive auxotrophy and adaptations to the intestinal environment, Cell Host Microbe, 10, 260, 10.1016/j.chom.2011.08.005

Segata, 2013, PhyloPhlAn is a new method for improved phylogenetic and taxonomic placement of microbes, Nat Commun, 4, 2304, 10.1038/ncomms3304

Segata, 2011, Metagenomic biomarker discovery and explanation, Genome Biol, 12, R60, 10.1186/gb-2011-12-6-r60

Segata, 2012, Metagenomic microbial community profiling using unique clade-specific marker genes, Nat Methods, 9, 811, 10.1038/nmeth.2066

Singh, 2012, 2012 update of the 2008 American College of Rheumatology recommendations for the use of disease-modifying antirheumatic drugs and biologic agents in the treatment of rheumatoid arthritis, Arthritis Care Res (Hoboken), 64, 625, 10.1002/acr.21641

Stahl, 2010, Genome-wide association study meta-analysis identifies seven new rheumatoid arthritis risk loci, Nat Genet, 42, 508, 10.1038/ng.582

Tao, 2011, IL-10 signaling in CD4+ T cells is critical for the pathogenesis of collagen-induced arthritis, Arthritis Res Ther, 13, R212, 10.1186/ar3545

Tillett, 1930, Serological reactions in pneumonia with a non-protein somatic fraction of Pneumococcus, J Exp Med, 52, 561, 10.1084/jem.52.4.561

Ubeda, 2010, Vancomycin-resistant Enterococcus domination of intestinal microbiota is enabled by antibiotic treatment in mice and precedes bloodstream invasion in humans, J Clin Invest, 120, 4332, 10.1172/JCI43918

Wang, 2007, Naive Bayesian classifier for rapid assignment of rRNA sequences into the new bacterial taxonomy, Appl Environ Microbiol, 73, 5261, 10.1128/AEM.00062-07

Winter, 2013, Host-derived nitrate boosts growth of E. coli in the inflamed gut, Science, 339, 708, 10.1126/science.1232467

Wu, 2011, Linking long-term dietary patterns with gut microbial enterotypes, Science, 334, 105, 10.1126/science.1208344

Wu, 2010, Gut-residing segmented filamentous bacteria drive autoimmune arthritis via T helper 17 cells, Immunity, 32, 815, 10.1016/j.immuni.2010.06.001

Yatsunenko, 2012, Human gut microbiome viewed across age and geography, Nature, 486, 222, 10.1038/nature11053

Zanin-Zhorov, 2010, Protein kinase C-theta mediates negative feedback on regulatory T cell function, Science, 328, 372, 10.1126/science.1186068

Zhu, 2010, Ab initio gene identification in metagenomic sequences, Nucleic Acids Res, 38, e132, 10.1093/nar/gkq275