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Cell Host Microbe. 2018 Oct 10;24(4):600-610.e4. doi: 10.1016/j.chom.2018.09.009.

Compositional and Temporal Changes in the Gut Microbiome of Pediatric Ulcerative Colitis Patients Are Linked to Disease Course.

Author information

1
The Broad Institute of MIT and Harvard, Infectious Disease and Microbiome, Cambridge, MA 02142, USA; Harvard T.H. Chan School of Public Health, Biostatistics Department, Boston, MA 02115, USA.
2
Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
3
The Broad Institute of MIT and Harvard, Infectious Disease and Microbiome, Cambridge, MA 02142, USA; Center for Microbiome Informatics and Therapeutics, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA.
4
Collaborative Studies Coordinating Center, Department of Biostatistics, University of North Carolina, Chapel Hill, NC 27516, USA; RTI International, Biostatistics and Epidemiology Division, Research Triangle Park, NC 27709, USA.
5
Collaborative Studies Coordinating Center, Department of Biostatistics, University of North Carolina, Chapel Hill, NC 27516, USA.
6
Children's Hospital Boston, Boston, MA 02115, USA.
7
Women and Children's Hospital of Buffalo WCHOB, Buffalo, NY 14222, USA.
8
Emory Children's Center, Atlanta, GA 30322, USA.
9
Cohen Children's Medical Center, Pediatric Gastroenterology, New York, NY 11040, USA.
10
Riley Children's Hospital Indiana University, School of Medicine, Section of Gastroenterology/Hepatology/Nutrition, Indianapolis, IN 46202, USA.
11
Johns Hopkins Children's Center, Department of Pediatrics, Baltimore, MD 21287, USA.
12
Goryeb Children's Hospital/Atlantic Health, Pediatric Gastroenterology, Morristown, NJ 07960, USA.
13
IWK Health Centre, Division of Gastroenterology and Nutrition, Halifax, NS B3K 6R8, Canada.
14
Nationwide Children's Hospital, Pediatrics, Columbus, OH 43205, USA.
15
Children's Hospital of Eastern Ontario and University of Ottawa, Department of Pediatrics, Ottawa, ON K1H 8L1, Canada.
16
Children's Hospital of Philadelphia CHOP, Pediatric Gastroenterologist, Philadelphia, PA 19104, USA.
17
UPMC Children's Hospital of Pittsburgh, Department of Pediatrics, Pittsburgh, PA 15224, USA.
18
Hasbro Children's Hospital, Pediatric Gastroenterology, Providence, RI 02903, USA.
19
University of California at San Francisco, Pediatric Gastroenterology, San Francisco, CA 94158, USA.
20
Sickkids Hospital, University of Toronto, Gastroenterology, Hepatology and Nutrition, Toronto, ON M5G 1X8, Canada.
21
UT Southwestern, Department of Pediatrics, Dallas, TX 75390, USA.
22
Medical College of Wisconsin, Gastroenterology, Milwaukee, WI 53226, USA.
23
Connecticut Children's Medical Center, Division of Digestive Diseases, Hartford, CT 06106, USA.
24
The Broad Institute of MIT and Harvard, Infectious Disease and Microbiome, Cambridge, MA 02142, USA; Center for Computational and Integrative Biology, Massachusetts General Hospital, Boston, MA 02114, USA; Gastrointestinal Unit and Center for the Study of Inflammatory Bowel Disease, Massachusetts General Hospital, Boston, MA 02114, USA; Center for Microbiome Informatics and Therapeutics, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA. Electronic address: xavier@molbio.mgh.harvard.edu.

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.

KEYWORDS:

5ASA; colectomy; corticosteroids; disease course; gut microbiome; host-microbial interactions; pediatric ulcerative colitis; response to therapy; serological markers; treatment-naive

PMID:
30308161
PMCID:
PMC6277984
[Available on 2019-10-10]
DOI:
10.1016/j.chom.2018.09.009
[Indexed for MEDLINE]

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