Genes and environment contribute to IBD

Inflammatory bowel disease (IBD), comprising different diseases of the colon and small intestines such as Crohn’s disease (CD) and ulcerative colitis (UC), are autoimmune diseases whereby the body’s immune system attacks its own tissues, causing chronic inflammation, abdominal pain, cramps, diarrhea, fever and weight loss. The ultimate cause(s) of IBD is unknown but current medical research has implicated both genetic and environmental considerations and their complex interplay. As with many diseases, the relative importance of genetics versus environmental factors in development of IBD is not clear and is under active investigation.

There is evidence that more than 160 genes are implicated in causing Crohn’s disease, ulcerative colitis, or both

The role of the gut microbiome and your body’s reaction

Environmental factors that increase the risk of IBD in genetically-predisposed individuals include diet, sanitation and especially, exposure to microbes. Research has shown that the type and extent of colonization of the digestive system by bacteria, fungi and viruses (collectively called the gut microbiome or microbiota) plays an important role in increasing risk of IBD; changes in the composition of the gut microbiome, including an increase in pathogenic bacteria, decrease in bacteria that are considered “anti-inflammatory”, and a drop in the overall diversity of the microbiome have all been observed (Source). Recent work in mice has shown that food preservatives affect the integrity of the intestine, leading to increased penetration into the intestinal wall by bacteria; the immune system responds by increasing inflammation which is the hallmark of UC.

Many of the genes implicated in inflammatory bowel disease susceptibility function in the immune system and its response to the gut microbiome

At least 160 genes have been implicated in crohn’s and colitis

In terms of the genetic factors, studies have implicated numerous genetic variants as risk factors for IBD. In fact, there is evidence that more than 160 genes (and counting as discovery efforts continue) are implicated in causing CD, UC, or both. In general, most of the genetic variants increase IBD risk by small amounts, however, there are some that are clear drivers of the disease (Source). Alterations in the NOD2, IL23R, IL10, ATG16L1 and the recently discovered HLA-DRB1 genes are considered key susceptibility determinants. Individuals containing single genetic variants (the “monogenic” genotype) are rare but when present can lead to childhood or early-onset IBD. For eight of the monogenic variations implicated in IBD, a functional understanding connecting gene to disease is well understood (link); for example, research has shown that the protein product of the NOD2 gene is found on the outer surface of the small intestine, senses the presence of bacteria and triggers product of bacteria-killing secretions. The gene is defective in certain populations and in these subjects have increased bacterial invasion and increased susceptibility to IBD.

For certain populations, personalized medicine and management of IBD has begun

For adult IBD, it is thought that a combination of multiple genetic alterations (“oligogenic” or “polygenic” genotypes) is necessary to cause disease. For the vast majority of the identified genetic variants in polygenic IBD, a functional understanding of how, and how much, these contribute to the pathogenesis and development of the disease is lacking. It is clear that many of the genes implicated in IBD susceptibility function in the immune system and its response to gut microbiome and research is ongoing to develop mechanistic understanding of these variants.

Genetic screening for IBD has already begun

At this time, predictability of disease risk using purely genetic considerations is complex and therefore environmental factors need to be considered. Yet for certain populations, personalized medicine and management of IBD has begun. Genetic screening for monogenic IBD informs treatment options. Research is focusing on understanding the molecular mechanisms of development of IBD, how each gene contributes to the disease, and the identification of populations containing key genetic variants. With this knowledge, discovery and development of novel therapeutic interventions or lifestyle changes will follow.

What’s next?

We are on the cusp of true genetic diagnosis, prediction of disease, personalized medicine / intervention and management of IBD like Crohn’s and colitis. It is an exciting time in IBD research, with the cost and power of exome sequencing like that used in GeneYouIn’s VitaSeqTM available to untangle the ultimate genetic causes of IBD. VitaSeqTM sequences your entire exome and could help you identify your susceptibility to IBD. If you’ve enjoyed this article, please share it with your friends and family and read more about how genetic testing can help you predict your risk of inherited diseases. GeneYouIn is also continuously optimizing our screenings tools, so be sure to follow our blog and on Facebook and Twitter for the latest news in genetic diagnosis of autoimmune diseases.

Image source: “Mechanisms of Disease: pathogenesis of Crohn’s disease and ulcerative colitis”
R Balfour Sartor. Nature Clinical Practice Gastroenterology & Hepatology. (2006) 3, 390-407

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