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Genome Med. 2016 Jul 13;8(1):75. doi: 10.1186/s13073-016-0331-y.

Dysbiosis, inflammation, and response to treatment: a longitudinal study of pediatric subjects with newly diagnosed inflammatory bowel disease.

Author information

1
Graduate Program in Genetics and Molecular Biology, Graduate Division of Biological and Biomedical Sciences, Emory University, Atlanta, GA, 30322, USA.
2
Department of Pediatrics, Emory University School of Medicine & Children's Healthcare of Atlanta, 2015 Uppergate Drive, room 248, Atlanta, GA, 30322, USA.
3
Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA.
4
Department of Computer Science, Aalto University School of Science, 02150, Espoo, Finland.
5
Department of Human Genetics, Emory University, Atlanta, GA, 30322, USA.
6
Centers for Disease Control and Prevention, Atlanta, GA, 30341, USA.
7
Center for Computational and Integrative Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114, USA.
8
Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA, 30322, USA.
9
Department of Pediatrics, Emory University School of Medicine & Children's Healthcare of Atlanta, 2015 Uppergate Drive, room 248, Atlanta, GA, 30322, USA. skugath@emory.edu.
10
Department of Human Genetics, Emory University, Atlanta, GA, 30322, USA. skugath@emory.edu.

Abstract

BACKGROUND:

Gut microbiome dysbiosis has been demonstrated in subjects with newly diagnosed and chronic inflammatory bowel disease (IBD). In this study we sought to explore longitudinal changes in dysbiosis and ascertain associations between dysbiosis and markers of disease activity and treatment outcome.

METHODS:

We performed a prospective cohort study of 19 treatment-naïve pediatric IBD subjects and 10 healthy controls, measuring fecal calprotectin and assessing the gut microbiome via repeated stool samples. Associations between clinical characteristics and the microbiome were tested using generalized estimating equations. Random forest classification was used to predict ultimate treatment response (presence of mucosal healing at follow-up colonoscopy) or non-response using patients' pretreatment samples.

RESULTS:

Patients with Crohn's disease had increased markers of inflammation and dysbiosis compared to controls. Patients with ulcerative colitis had even higher inflammation and dysbiosis compared to those with Crohn's disease. For all cases, the gut microbial dysbiosis index associated significantly with clinical and biological measures of disease severity, but did not associate with treatment response. We found differences in specific gut microbiome genera between cases/controls and responders/non-responders including Akkermansia, Coprococcus, Fusobacterium, Veillonella, Faecalibacterium, and Adlercreutzia. Using pretreatment microbiome data in a weighted random forest classifier, we were able to obtain 76.5 % accuracy for prediction of responder status.

CONCLUSIONS:

Patient dysbiosis improved over time but persisted even among those who responded to treatment and achieved mucosal healing. Although dysbiosis index was not significantly different between responders and non-responders, we found specific genus-level differences. We found that pretreatment microbiome signatures are a promising avenue for prediction of remission and response to treatment.

KEYWORDS:

Crohn’s disease; Dysbiosis; Inflammatory bowel disease; Microbiome

PMID:
27412252
PMCID:
PMC4944441
DOI:
10.1186/s13073-016-0331-y
[Indexed for MEDLINE]
Free PMC Article

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