@article{81b5bf6ccdfb47dbaf6000ecb9e91e3c,
title = "Compositional and Temporal Changes in the Gut Microbiome of Pediatric Ulcerative Colitis Patients Are Linked to Disease Course",
abstract = "Evaluating progression risk and determining optimal therapy for ulcerative colitis (UC) is challenging as many patients exhibit incomplete responses to treatment. As part of the PROTECT (Predicting Response to Standardized Colitis Therapy) Study, we evaluated the role of the gut microbiome in disease course for 405 pediatric, new-onset, treatment-naive UC patients. Patients were monitored for 1 year upon treatment initiation, and microbial taxonomic composition was analyzed from fecal samples and rectal biopsies. Depletion of core gut microbes and expansion of bacteria typical of the oral cavity were associated with baseline disease severity. Remission and refractory disease were linked to species-specific temporal changes that may be implicative of therapy efficacy, and a pronounced increase in microbiome variability was observed prior to colectomy. Finally, microbial associations with disease-associated serological markers suggest host-microbial interactions in UC. These insights will help improve existing treatments and develop therapeutic approaches guiding optimal medical care. Many patients exhibit incomplete responses to ulcerative colitis (UC) therapy. Schirmer et al. investigate the gut microbiome's role in pediatric UC treated with two conventional therapies. Baseline and longitudinal microbial trends are implicated in disease severity and progression, including remission and colectomy requirement. These insights may motivate new therapeutic approaches.",
keywords = "5ASA, colectomy, corticosteroids, disease course, gut microbiome, host-microbial interactions, pediatric ulcerative colitis, response to therapy, serological markers, treatment-naive",
author = "Melanie Schirmer and Lee Denson and Hera Vlamakis and Franzosa, {Eric A.} and Sonia Thomas and Gotman, {Nathan M.} and Paul Rufo and Baker, {Susan S.} and Cary Sauer and James Markowitz and Marian Pfefferkorn and Maria Oliva-Hemker and Joel Rosh and Anthony Otley and Brendan Boyle and David Mack and Robert Baldassano and David Keljo and Neal LeLeiko and Melvin Heyman and Anne Griffiths and Patel, {Ashish S.} and Joshua Noe and Subra Kugathasan and Thomas Walters and Curtis Huttenhower and Jeffrey Hyams and Xavier, {Ramnik J.}",
note = "Funding Information: We thank the PROTECT cohort for their participation. This study was supported by grants from the NIH ( 5U01DK095745 , P30DK043351 , and R01AT009708 ), Center for Microbiome Informatics and Therapeutics , and Crohn's and Colitis Foundation to R.J.X. and NIH grant U54DK102557 to C.H. and R.J.X. We thank Tiffany Poon (Broad Institute) for help in sequence production and sample management, Jason Bishai (Broad Institute) for help with sample processing, Bahar Sayoldin (Broad Institute) for making the data available through the SRA, and Theresa Reimels (MGH) for invaluable editorial help. Funding Information: We thank the PROTECT cohort for their participation. This study was supported by grants from the NIH (5U01DK095745, P30DK043351, and R01AT009708), Center for Microbiome Informatics and Therapeutics, and Crohn's and Colitis Foundation to R.J.X. and NIH grant U54DK102557 to C.H. and R.J.X. We thank Tiffany Poon (Broad Institute) for help in sequence production and sample management, Jason Bishai (Broad Institute) for help with sample processing, Bahar Sayoldin (Broad Institute) for making the data available through the SRA, and Theresa Reimels (MGH) for invaluable editorial help. Funding Information: J.H.: advisory board, Janssen; consultant, Abbvie, Takeda, Lilly, Boerhinger-Ingelheim, Allergan, Pfizer, Receptos, and Astra Zeneca; S.T.: independent data monitoring committee, Lycera Corporation; L.D.: grant support, AbbVie and Janssen; N.L.: consultant, Abbvie; A.S.P.: speakers bureau, Abbvie and Janssen; J.M.: consultant, Janssen, Celgene, and Lilly; M.O.-H.: grant support, Abbott Immunology and Janssen; consultant, Hoffman LaRoche; A.G.: research support, Abbvie; consultant, Abbvie, Celgene, Janssen, Lilly, Pfizer, and Takeda; speaker, Abbvie, Janssen, and Shire; J.R.: consultant, Abbvie, Celgene, Janssen, Luitpold, and Pfizer; grant funding, Janssen and Abbive; D.K.: research support, Genentech and Takeda; A.O.: advisory board, Janssen and Abbvie; research support, Lilly, Abbvie, Janssen, Takeda, and Celgene; P.R.: consultant, Shire and Leutpold; speaker, Abbvie; research support, TechLab; C.S.: consultant, Abbvie; S.K.: consultant, Janssen and UCB; M.H.: research grants, Genentech, Abbvie, Shire, Takeda, Mallinkrodt, Janssen, and Gilead; C.H.: advisory board, Seres Scientific. Publisher Copyright: {\textcopyright} 2018 Elsevier Inc. Copyright: Copyright 2018 Elsevier B.V., All rights reserved.",
year = "2018",
month = oct,
day = "10",
doi = "10.1016/j.chom.2018.09.009",
language = "English (US)",
volume = "24",
pages = "600--610.e4",
journal = "Cell Host and Microbe",
issn = "1931-3128",
publisher = "Cell Press",
number = "4",
}