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Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Pathophysiol. Nov 15, 2015; 6(4): 159-168
Published online Nov 15, 2015. doi: 10.4291/wjgp.v6.i4.159
Host-microbiome interaction in Crohn’s disease: A familiar or familial issue?
Andrea Michielan, Renata D’Incà
Andrea Michielan, Renata D’Incà, Department of Surgical, Oncological and Gastroenterological Sciences, Azienda Ospedaliera - Università degli Studi di Padova, 35128 Padova, Italy
Author contributions: Michielan A contributed to concept and drafting of the manuscript; D’Incà R contributed to critical revision for important intellectual content.
Conflict-of-interest statement: Authors declare no conflict of interests for this article.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Andrea Michielan, MD, Department of Surgical, Oncological and Gastroenterological Sciences, Azienda Ospedaliera - Università degli Studi di Padova, Via Giustiniani 2, 35128 Padova, Italy. andreamichielan@virgilio.it
Telephone: +39-04-98212893 Fax: +39-04-98760820
Received: June 24, 2015
Peer-review started: June 24, 2015
First decision: August 25, 2015
Revised: September 13, 2015
Accepted: October 23, 2015
Article in press: October 27, 2015
Published online: November 15, 2015
Processing time: 146 Days and 12 Hours
Abstract

An impaired interaction between the gut and the intestinal microbiome is likely to be the key element in the pathogenesis of Crohn’s disease (CD). Family studies have provided invaluable information on CD pathogenesis and on its etiology. Relatives share the same genetic risk of developing the disease as affected subjects. Relatives also exhibit similar features relating to their host-microbiome interaction, namely genetic variants in loci involved in detecting bacteria, a greater sero-reactivity to microbial components, and an impaired intestinal permeability. The burden of environmental factors such as cigarette smoking and dysbiosis also seems to be particularly relevant in these genetically predisposed subjects. Diet is emerging as an important factor and could account for the changing epidemiology of CD in recent years. Despite the pivotal role of genetics in the disease’s pathogenesis (especially in familial CD), screening tests in healthy relatives cannot be recommended.

Keywords: Crohn’s disease; Genetics; Environment; Microbiome; Relatives

Core tip: Family studies support a host-microbiome interaction in the development of Crohn’s disease (CD). Unaffected relatives reveal genetic variants in loci involved in detecting bacteria, a greater sero-reactivity to microbial components, an impaired intestinal permeability, and a greater susceptibility to environmental factors. Whether genetic or environmental factors drive these conditions is still under investigation, but CD pathogenesis is very likely multifactorial. A genetic burden may be hypothesized in familial CD, while environmental factors may be predominant in sporadic CD.