The treatment-naive microbiome in new-onset Crohn's disease

Dirk Gevers; Subra Kugathasan; Lee A. Denson; Yoshiki Vázquez-Baeza; Will Van Treuren; Boyu Ren; Emma Schwager; Dan Knights; Se Jin Song; Moran Yassour; Xochitl C. Morgan; Aleksandar D. Kostic; Chengwei Luo; Antonio González; Daniel McDonald; Yael Haberman; Thomas Walters; Susan Baker; Joel Rosh; Michael Stephens; Melvin Heyman; James Markowitz; Robert Baldassano; Anne Griffiths; Francisco Sylvester; David Mack; Sandra Kim; Wallace Crandall; Jeffrey Hyams; Curtis Huttenhower; Rob Knight; Ramnik J. Xavier

doi:10.1016/j.chom.2014.02.005

The treatment-naive microbiome in new-onset Crohn's disease

Dirk Gevers, Subra Kugathasan, Lee A. Denson, Yoshiki Vázquez-Baeza, Will Van Treuren, Boyu Ren, Emma Schwager, Dan Knights, Se Jin Song, Moran Yassour, Xochitl C. Morgan, Aleksandar D. Kostic, Chengwei Luo, Antonio González, Daniel McDonald, Yael Haberman, Thomas Walters, Susan Baker, Joel Rosh, Michael StephensMelvin Heyman, James Markowitz, Robert Baldassano, Anne Griffiths, Francisco Sylvester, David Mack, Sandra Kim, Wallace Crandall, Jeffrey Hyams, Curtis Huttenhower, Rob Knight, Ramnik J. Xavier^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

2380 Scopus citations

Abstract

Inflammatory bowel diseases (IBDs), including Crohn's disease (CD), are genetically linked to host pathways that implicate an underlying role for aberrant immune responses to intestinal microbiota. However, patterns of gut microbiome dysbiosis in IBD patients are inconsistent among published studies. Using samples from multiple gastrointestinal locations collected prior to treatment in new-onset cases, we studied the microbiome in the largest pediatric CD cohort to date. An axis defined by an increased abundance in bacteria which include Enterobacteriaceae, Pasteurellacaea, Veillonellaceae, and Fusobacteriaceae, and decreased abundance in Erysipelotrichales, Bacteroidales, and Clostridiales, correlates strongly with disease status. Microbiome comparison between CD patients with and without antibiotic exposure indicates that antibiotic use amplifies the microbial dysbiosis associated with CD. Comparing the microbial signatures between the ileum, the rectum, and fecal samples indicates that at this early stage of disease, assessing the rectal mucosal-associated microbiome offers unique potential for convenient and early diagnosis of CD.

Original language	English
Pages (from-to)	382-392
Number of pages	11
Journal	Cell Host and Microbe
Volume	15
Issue number	3
DOIs	https://doi.org/10.1016/j.chom.2014.02.005
State	Published - 12 Mar 2014
Externally published	Yes

Bibliographical note

Funding Information:
We thank the patients who donated samples for this study, the health professionals who collected them, and the Crohn’s and Colitis Foundation of America for supporting the RISK cohort. We thank Douglas Wendel, Gail Ackermann, Tim Vigers, and Tim L. Tickle for their valuable input and helpful discussions. We thank participating clinicians Marla Dubinsky, Joshua Noe, Scott Snapper, Richard Kellermayer, Michael Kappleman, Anthony Otley, Mirian Pfefferkorn, Stanley Cohen, Stephen Guthery, Neal LeLeiko, Maria Oliva-Hemker, David Keljo, Dedrick Moulton, Barbara Kircshner, Ashish Patel, David Ziring, Jonathan Evans, Jonah Essers, Bruce Aronow, and MiOk Kim. Work was supported by grants from the Crohn’s and Colitis Foundation of America, The Leona M. and Harry B. Helmsley Charitable Trust, ARO grant W911NF-11-1-0473 (C.H.), and by NIH grants U54 DE023798, R01 HG005969 (C.H.), and R01 DK092405 (R.J.X., C.H., and D.G.).

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Gevers, D., Kugathasan, S., Denson, L. A., Vázquez-Baeza, Y., Van Treuren, W., Ren, B., Schwager, E., Knights, D., Song, S. J., Yassour, M., Morgan, X. C., Kostic, A. D., Luo, C., González, A., McDonald, D., Haberman, Y., Walters, T., Baker, S., Rosh, J., ... Xavier, R. J. (2014). The treatment-naive microbiome in new-onset Crohn's disease. Cell Host and Microbe, 15(3), 382-392. https://doi.org/10.1016/j.chom.2014.02.005

@article{14d1be90fd0944ba900cd22387934795,

title = "The treatment-naive microbiome in new-onset Crohn's disease",

abstract = "Inflammatory bowel diseases (IBDs), including Crohn's disease (CD), are genetically linked to host pathways that implicate an underlying role for aberrant immune responses to intestinal microbiota. However, patterns of gut microbiome dysbiosis in IBD patients are inconsistent among published studies. Using samples from multiple gastrointestinal locations collected prior to treatment in new-onset cases, we studied the microbiome in the largest pediatric CD cohort to date. An axis defined by an increased abundance in bacteria which include Enterobacteriaceae, Pasteurellacaea, Veillonellaceae, and Fusobacteriaceae, and decreased abundance in Erysipelotrichales, Bacteroidales, and Clostridiales, correlates strongly with disease status. Microbiome comparison between CD patients with and without antibiotic exposure indicates that antibiotic use amplifies the microbial dysbiosis associated with CD. Comparing the microbial signatures between the ileum, the rectum, and fecal samples indicates that at this early stage of disease, assessing the rectal mucosal-associated microbiome offers unique potential for convenient and early diagnosis of CD.",

author = "Dirk Gevers and Subra Kugathasan and Denson, {Lee A.} and Yoshiki V{\'a}zquez-Baeza and {Van Treuren}, Will and Boyu Ren and Emma Schwager and Dan Knights and Song, {Se Jin} and Moran Yassour and Morgan, {Xochitl C.} and Kostic, {Aleksandar D.} and Chengwei Luo and Antonio Gonz{\'a}lez and Daniel McDonald and Yael Haberman and Thomas Walters and Susan Baker and Joel Rosh and Michael Stephens and Melvin Heyman and James Markowitz and Robert Baldassano and Anne Griffiths and Francisco Sylvester and David Mack and Sandra Kim and Wallace Crandall and Jeffrey Hyams and Curtis Huttenhower and Rob Knight and Xavier, {Ramnik J.}",

note = "Funding Information: We thank the patients who donated samples for this study, the health professionals who collected them, and the Crohn{\textquoteright}s and Colitis Foundation of America for supporting the RISK cohort. We thank Douglas Wendel, Gail Ackermann, Tim Vigers, and Tim L. Tickle for their valuable input and helpful discussions. We thank participating clinicians Marla Dubinsky, Joshua Noe, Scott Snapper, Richard Kellermayer, Michael Kappleman, Anthony Otley, Mirian Pfefferkorn, Stanley Cohen, Stephen Guthery, Neal LeLeiko, Maria Oliva-Hemker, David Keljo, Dedrick Moulton, Barbara Kircshner, Ashish Patel, David Ziring, Jonathan Evans, Jonah Essers, Bruce Aronow, and MiOk Kim. Work was supported by grants from the Crohn{\textquoteright}s and Colitis Foundation of America, The Leona M. and Harry B. Helmsley Charitable Trust, ARO grant W911NF-11-1-0473 (C.H.), and by NIH grants U54 DE023798, R01 HG005969 (C.H.), and R01 DK092405 (R.J.X., C.H., and D.G.). ",

year = "2014",

month = mar,

day = "12",

doi = "10.1016/j.chom.2014.02.005",

language = "אנגלית",

volume = "15",

pages = "382--392",

journal = "Cell Host and Microbe",

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Gevers, D, Kugathasan, S, Denson, LA, Vázquez-Baeza, Y, Van Treuren, W, Ren, B, Schwager, E, Knights, D, Song, SJ, Yassour, M, Morgan, XC, Kostic, AD, Luo, C, González, A, McDonald, D, Haberman, Y, Walters, T, Baker, S, Rosh, J, Stephens, M, Heyman, M, Markowitz, J, Baldassano, R, Griffiths, A, Sylvester, F, Mack, D, Kim, S, Crandall, W, Hyams, J, Huttenhower, C, Knight, R & Xavier, RJ 2014, 'The treatment-naive microbiome in new-onset Crohn's disease', Cell Host and Microbe, vol. 15, no. 3, pp. 382-392. https://doi.org/10.1016/j.chom.2014.02.005

TY - JOUR

T1 - The treatment-naive microbiome in new-onset Crohn's disease

AU - Gevers, Dirk

AU - Kugathasan, Subra

AU - Denson, Lee A.

AU - Vázquez-Baeza, Yoshiki

AU - Van Treuren, Will

AU - Ren, Boyu

AU - Schwager, Emma

AU - Knights, Dan

AU - Song, Se Jin

AU - Yassour, Moran

AU - Morgan, Xochitl C.

AU - Kostic, Aleksandar D.

AU - Luo, Chengwei

AU - González, Antonio

AU - McDonald, Daniel

AU - Haberman, Yael

AU - Walters, Thomas

AU - Baker, Susan

AU - Rosh, Joel

AU - Stephens, Michael

AU - Heyman, Melvin

AU - Markowitz, James

AU - Baldassano, Robert

AU - Griffiths, Anne

AU - Sylvester, Francisco

AU - Mack, David

AU - Kim, Sandra

AU - Crandall, Wallace

AU - Hyams, Jeffrey

AU - Huttenhower, Curtis

AU - Knight, Rob

AU - Xavier, Ramnik J.

N1 - Funding Information: We thank the patients who donated samples for this study, the health professionals who collected them, and the Crohn’s and Colitis Foundation of America for supporting the RISK cohort. We thank Douglas Wendel, Gail Ackermann, Tim Vigers, and Tim L. Tickle for their valuable input and helpful discussions. We thank participating clinicians Marla Dubinsky, Joshua Noe, Scott Snapper, Richard Kellermayer, Michael Kappleman, Anthony Otley, Mirian Pfefferkorn, Stanley Cohen, Stephen Guthery, Neal LeLeiko, Maria Oliva-Hemker, David Keljo, Dedrick Moulton, Barbara Kircshner, Ashish Patel, David Ziring, Jonathan Evans, Jonah Essers, Bruce Aronow, and MiOk Kim. Work was supported by grants from the Crohn’s and Colitis Foundation of America, The Leona M. and Harry B. Helmsley Charitable Trust, ARO grant W911NF-11-1-0473 (C.H.), and by NIH grants U54 DE023798, R01 HG005969 (C.H.), and R01 DK092405 (R.J.X., C.H., and D.G.).

PY - 2014/3/12

Y1 - 2014/3/12

N2 - Inflammatory bowel diseases (IBDs), including Crohn's disease (CD), are genetically linked to host pathways that implicate an underlying role for aberrant immune responses to intestinal microbiota. However, patterns of gut microbiome dysbiosis in IBD patients are inconsistent among published studies. Using samples from multiple gastrointestinal locations collected prior to treatment in new-onset cases, we studied the microbiome in the largest pediatric CD cohort to date. An axis defined by an increased abundance in bacteria which include Enterobacteriaceae, Pasteurellacaea, Veillonellaceae, and Fusobacteriaceae, and decreased abundance in Erysipelotrichales, Bacteroidales, and Clostridiales, correlates strongly with disease status. Microbiome comparison between CD patients with and without antibiotic exposure indicates that antibiotic use amplifies the microbial dysbiosis associated with CD. Comparing the microbial signatures between the ileum, the rectum, and fecal samples indicates that at this early stage of disease, assessing the rectal mucosal-associated microbiome offers unique potential for convenient and early diagnosis of CD.

AB - Inflammatory bowel diseases (IBDs), including Crohn's disease (CD), are genetically linked to host pathways that implicate an underlying role for aberrant immune responses to intestinal microbiota. However, patterns of gut microbiome dysbiosis in IBD patients are inconsistent among published studies. Using samples from multiple gastrointestinal locations collected prior to treatment in new-onset cases, we studied the microbiome in the largest pediatric CD cohort to date. An axis defined by an increased abundance in bacteria which include Enterobacteriaceae, Pasteurellacaea, Veillonellaceae, and Fusobacteriaceae, and decreased abundance in Erysipelotrichales, Bacteroidales, and Clostridiales, correlates strongly with disease status. Microbiome comparison between CD patients with and without antibiotic exposure indicates that antibiotic use amplifies the microbial dysbiosis associated with CD. Comparing the microbial signatures between the ileum, the rectum, and fecal samples indicates that at this early stage of disease, assessing the rectal mucosal-associated microbiome offers unique potential for convenient and early diagnosis of CD.

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SN - 1931-3128

VL - 15

SP - 382

EP - 392

JO - Cell Host and Microbe

JF - Cell Host and Microbe

IS - 3

ER -

The treatment-naive microbiome in new-onset Crohn's disease

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Bibliographical note

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