Research Article
Colonic Mucosal Epigenome and Microbiome Development in
Children and Adolescents
R. Alan Harris,
1
Rajesh Shah,
2
Emily B. Hollister,
3,4
Rune Rose Tronstad,
5,6
Nils Hovdenak,
7
Reka Szigeti,
3
James Versalovic,
3,4
and Richard Kellermayer
4,8,9
1
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA
2
Section of Gastroenterology and Hepatology, Baylor College of Medicine, Houston, TX 77030, USA
3
Department of Pathology & Immunology, Baylor College of Medicine, Houston, TX 77030, USA
4
Texas Children’s Hospital, Houston, TX 77030, USA
5
Department of Clinical Science, University of Bergen, 5020 Bergen, Norway
6
Department of Pediatrics, Haukeland University Hospital, 5021 Bergen, Norway
7
Department of Clinical Medicine, University of Bergen, 5020 Bergen, Norway
8
Section of Pediatric Gastroenterology, Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA
9
USDA/ARS Children’s Nutrition Research Center, Houston, TX 77030, USA
Correspondence should be addressed to Richard Kellermayer; kellerma@bcm.edu
Received 18 August 2015; Revised 12 January 2016; Accepted 17 January 2016
Academic Editor: Kurt Blaser
Copyright © 2016 R. Alan Harris et al. Tis is an open access article distributed under the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Epigenetic and microbiome changes during pediatric development have been implicated as important elements in the
developmental origins of infammatory bowel diseases (IBDs) including Crohn’s disease (CD) and ulcerative colitis (UC), which
are linked to early onset colorectal cancer (CRC). Colonic mucosal samples from 22 control children between 3.5 and 17.5 years of
age were studied by Infnium HumanMethylation450 BeadChips and, in 10 cases, by 454 pyrosequencing of the bacterial 16S rRNA
gene. Intercalating age-specifc DNA methylation and microbiome changes were identifed, which may have signifcant translational
relevance in the developmental origins of IBD and CRC.
1. Introduction
Te epidemiology of infammatory bowel diseases (IBDs)
strongly implicates their environmental origin [1]. IBDs
(Crohn’s disease (CD) and ulcerative colitis (UC)) afect
close to 1 in every 200 people just in the United States
[2]. Tere has been a 5–10-fold increase in the prevalence
of CD and a 2–10-fold increase in the prevalence of UC
over the past 5-6 decades in developed countries [3, 4].
IBD incidence peaks in young adulthood, and its prevalence
appears to be continuously rising in children [5, 6]. Tis
epidemiology underscores the potential importance of the
pediatric developmental period in the pathogenesis of IBD.
While IBD is thought to be infuenced by genetics, host
immune dysfunction, mucosal barrier defects, and the gut
microbiome [7], the exact etiology remains unknown [1].
High monozygotic twin discordance rates and other
epidemiologic observations highlight the importance of non-
genetic (such as epigenetic) processes, which are vulnerable
to environmental (including nutritional) infuences, in the
etiology of IBD [1]. Te increased incidence of IBD in
populations migrating from low incidence to high incidence
areas of the world [8] also supports this contention. Tese
migration studies indicate that the prenatal and pediatric
developmental periods are the most important in regard to
the environmental developmental origins of IBD [1].
Te potential importance for epigenetics in IBD is only
recently receiving more attention [9]. Tere are many indi-
cations that epigenetic mechanisms other than DNA methy-
lation (the methylation of cytosine at CpG dinucleotides)
may contribute to the development, progression, and/or
maintenance of IBD, such as histone modifcations [10], and
Hindawi Publishing Corporation
Journal of Immunology Research
Volume 2016, Article ID 9170162, 7 pages
http://dx.doi.org/10.1155/2016/9170162