Determinants of IBD Heritability: Genes, Bugs, and More

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.

The impact of dietary fermentable carbohydrates on a postinflammatory model of irritable bowel syndrome

“…The higher abundance of Streptococcaceae and lower abundance of Lachnospiraceae in the low‐FODMAP diet group are of relevance to IBD as these changes are similar to that seen in patients with IBD. Lachnospiraceae have been shown to be depleted in IBD compared with non‐IBD controls and Streptococcaceae shown to be higher in IBD . Additionally, lower Lachnospiraceae promoted a heighted Th17 response in humanized germ‐free colitis, a potentially inflammatory effect, an effect which can be reversed with Lachnospiraceae supplementation .…”

“…Lachnospiraceae have been shown to be depleted in IBD compared with non-IBD controls 35 and Streptococcaceae shown to be higher in IBD. 36 Additionally, lower Lachnospiraceae promoted a heighted Th17 response in humanized germ-free colitis, a potentially inflammatory effect, an effect which can be reversed with Lachnospiraceae supplementation. 37 Lachnospiraceae degrade wheat bran (containing fructan), which may explain the differences seen.…”

Colitis ulcerosa: Kann eine Modulation der intestinalen Mikrobiota eine langfristige Remission bedingen?

“…das Krankheitsbild prägen. Bis zum heutigen Datum haben genomweite Assoziationsstudien (GWAS) und computergestützte (in silico) Metaanalysen zur Identifikation von mehr als 230 Risikogenen geführt (zur Übersicht siehe [10]). Da sich die CU in Darmabschnitten mit der höchsten Dichte von Mikroorganismen im menschlichen Körper manifestiert, wurde bereits früh eine pathophysiologische Verbindung zum intestinalen Mikrobiom vermutet [11].…”

The Multifactorial Etiopathogeneses Interplay of Inflammatory Bowel Disease: An Overview

“…Inflammatory bowel disease has been understood to be idiopathic attributable to several possible effectuates that include genetic, gut microbiota, dysbiosis; pollution, hygiene, environmental, immune response, urbanization and dietary/nutritional factors [44,45]. These factors, and more, are discussed point by point below.…”