Journal Article

Determinants of IBD Heritability: Genes, Bugs, and More

Williams Turpin, Ashleigh Goethel, Larbi Bedrani and Kenneth Croitoru, MDCM

in Inflammatory Bowel Diseases

Volume 24, issue 6, pages 1133-1148
Published in print May 2018 | ISSN: 1078-0998
Published online April 2018 | e-ISSN: 1536-4844 | DOI: https://dx.doi.org/10.1093/ibd/izy085
Determinants of IBD Heritability: Genes, Bugs, and More

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  • Medicine and Health
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  • Gastro-intestinal and Colorectal Surgery

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Abstract

Defining the etiology of inflammatory bowel disease (IBD) continues to elude researchers, in part due to the possibility that there may be different triggers for a spectrum of disease phenotypes that are currently classified as either Crohn’s disease (CD) or ulcerative colitis (UC). What is clear is that genetic susceptibility plays an important role in the development of IBD, and large genome-wide association studies using case-control approaches have identified more than 230 risk alleles. Many of these identified risk alleles are located in a variety of genes important in host-microbiome interactions. In spite of these major advances, the mechanisms behind the genetic influence on disease development remain unknown. In addition, the identified genetic risks have thus far failed to fully define the hereditability of IBD. Host genetics influence host interactions with the gut microbiota in maintaining health through a balance of regulated immune responses and coordinated microbial composition and function. What remains to be defined is how alterations in these interactions can lead to disease. The nature and cause of changes in the microbiota in patients with IBD are poorly understood. In spite of the large catalog of alterations in the microbiota of IBD patients, inflammation itself can alter the microbiota, leaving open the question of which is cause or effect. The composition and function of the gut microbiota are influenced by many factors, including environmental factors, dietary factors, and, as recent studies have shown, host genetic makeup. More than 200 loci have shown potential to influence the microbiota, but replication and larger studies are still required to validate these findings. It would seem reasonable to consider the combination of both host genetic makeup and the inheritance of the microbiota as interdependent heritable forces that could explain the nature of an individual’s susceptibility to IBD or indeed the actual cause of IBD. In this review, we will consider the contribution of the host genetics, the microbiome, and the influence of host genetics on the microbiota to the heritability of IBD.

Keywords: human microbiota; dysbiosis; inflammation; epigenetics

Journal Article.  10355 words.  Illustrated.

Subjects: Medicine and Health ; Clinical Medicine ; Gastroenterology ; Patient Education and Information ; Gastro-intestinal and Colorectal Surgery

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