Tag Archives: inflammatory bowel disease

New inflammatory bowel disease genes found

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A new study has identified 71 additional genetic associations for inflammatory bowel disease (IBD), many of which have been previously implicated in other immune-related disorders, including ankylosing spondylitis and psoriasis.

Crohn’s disease (CD) and ulcerative colitis (UC) – inflammatory diseases of the gastrointestinal tract – have puzzled the scientific community for decades.

The new research centres on these two diseases, which are collectively known as inflammatory bowel disease (IBD) and suggests a fundamental connection between risk of IBD and genes involved in other immune-related diseases and the immune system’s response to pathogens.

Researchers from the Broad Institute, Massachusetts General Hospital, Yale School of Medicine, Cedars-Sinai Medical Center, and dozens of other organizations work together in the study.

“This study marks the first time we’ve acquired and combined the raw data from so many research studies around the world and also the first time we’ve jointly analyzed Crohn’s with ulcerative colitis,” said author Mark Daly, one of the senior authors of the work and senior associate member of the Broad Institute and co-director of its Program in Medical and Population Genetics.

“We’ve been able, with this study, to evaluate the evidence for both diseases simultaneously, and discovered that the majority of genetic risk factors are associated with both diseases,” he stated.

Co-author Ramnik Xavier, a senior associate member of the Broad Institute, Chief of Gastroenterology and Director of the Center for the Study of Inflammatory Bowel Disease at MGH said, “There’s been a paradigm shift in our understanding of IBD. This gene discovery process offers an opportunity to begin identifying new targets for treatment, better diagnostic tools, and in the long-term, personalized care for patients.”

Inflammatory bowel disease

Inflammatory bowel disease

“We now have the necessary starting material to understand the pathways that contribute to Crohn’s disease and ulcerative colitis, and we also have a framework to better appreciate that they may not be two distinct diseases, but rather collections of many different diseases,” he added.

The new study not only brings together the original data from those previous analyses, but also adds genetic information from another 40,000 people either with or without a form of IBD.


It also suggests a strong overlap between IBD susceptibility genes and genes tied to the immune system’s response to mycobacterial infections, including tuberculosis and leprosy.

Researchers have observed similarities between the immune response in CD and that seen in tuberculosis and hypothesize that CD could be an aberrant response to certain harmless organisms present in the gut that trigger a similar reaction.

In addition to drawing upon original data from previous studies, the work utilizes a relatively new tool known as the immunochip, which samples 200,000 sites in the genome previously tied to autoimmune and inflammatory diseases.

“As a research community, we designed this array to target genes involved in immune-mediated diseases of all kinds. This is one of our first studies using the immunochip, and there are many more results that will emerge from these studies within IBD and across immune diseases,” said Daly.

At the Broad Institute, researchers are already pursuing some of the pathways identified in previous studies of UC and CD, including autophagy, a process in which infected cells eat themselves to combat microbes.

“This work gives us additional leads to pursue. It gives us an opportunity for high-quality, translational research, allowing us to identify core pathways involved in IBD and better understand how genes interact with each other and with the environment, illuminating new pathways that contribute to disease,” said Xavier.

Gut bacteria and IBD

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The rise of inflammatory bowel diseases could be down to our shifting diets causing a “boom in bad bacteria”, according to US researchers.

Mouse experiments detailed in the journal Nature linked certain fats, bacteria in the gut and the onset of inflammatory diseases.

The researchers said the high-fat diet changed the way food was digested and encouraged harmful bacteria.

Microbiologists said modifying gut bacteria might treat the disease.

Inflammatory bowel diseases (IBDs), such as Crohn’s and ulcerative colitis, affect one in every 350 people in the UK. When the gut becomes inflamed it can lead to abdominal pain and diarrhoea.

The researchers at the University of Chicago said the incidence of the diseases was increasing rapidly.

They used genetically modified mice which were more likely to develop IBDs. One in three developed colitis when fed either low-fat diets or meals high in polyunsaturated fats. This jumped to nearly two in three in those fed a diet high in saturated milk fats, which are in many processed foods.

Inflammatory bowel disease

Inflammatory bowel disease

These saturated fats are hard for the body to digest and it responds by pumping more bile into the gut. This changes the gut environment and leads to a change in the bacteria growing there, the researchers said.

One bacterium in particular, Bilophila wadsworthia, was identified. It thrives in the extra bile produced to break down the fats. It went from being incredibly rare to nearly 6% of all bacteria in the gut in the high-fat diet.


Prof Eugene Chang, of the University of Chicago, said: “Unfortunately, these can be harmful bacteria. Presented with a rich source of sulphur, they bloom, and when they do, they are capable of activating the immune system of genetically prone individuals.”

However, he said this could lead to possible treatments as the gut bacteria could be “reshaped” without “significantly affecting the lifestyles of individuals who are genetically prone to these diseases”.

Commenting on the research, Dr Roy Sleator, from the Cork Institute of Technology, said: “Not only do the authors provide, what is in my opinion, the first credible explanation as to how Western diet contributes to the unusually high incidence in inflammatory bowel disease; they also suggest an effective means of dealing with such diseases, by simply reshaping the microbial balance of the gut.”