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The Leaky Gut — Studied In Twins

How Crohn’s disease develops is still not really understood today. However, Swedish researchers say that a leaking intestinal wall could play an important role.

When they have a relapse, their lives often just happen between bed and toilet. People who suffer from Crohn’s disease have to live with the fact that their digestive tract inflames again and again. Again and again, they suffer from diarrhea, fever, pain, and abdominal cramps. But there are also times when patients feel much better. The cause of the disease is still unknown. Experts suspect both an inherited predisposition to the disease and environmental influences play a role. Smokers are affected much more frequently. Stress can cause a relapse but is not considered to be the cause of the disease.

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Since science knows how important an intact intestinal barrier is for health — it prevents pathogens and other harmful substances from penetrating into deeper tissue layers — researchers have found more and more indications of loopholes in the intestinal mucosa of Crohn’s disease patients. Scientists led by Ava Keita from Linköping University in Sweden have now investigated whether such a barrier disorder can also trigger the disease in twins (1).

There are observations that increased permeability in the intestinal wall is associated with an increased risk of relapse. This could suggest that the barrier disorder is a result of inflammation in the intestine. On the other hand, there are people who have hardly any symptoms but still have a barrier disorder. In addition, we know of genes that are related to both Crohn’s disease and the intestinal barrier.

If the barrier disorder is a genetic cause of Crohn’s disease, this would have to be shown above all in a very special group: twins. Swedish researchers have therefore now looked at 15 identical and fraternal pairs of twin siblings, one of each of which had Crohn’s disease; siblings were also included in the study. All twins were interviewed and underwent a colonoscopy; the doctors took samples from the intestinal wall during a biopsy.

When evaluating the data, the scientists found that the permeability between intestinal cells was increased in twins with Crohn’s disease compared to unrelated healthy individuals. However, it was also increased in the siblings of the patients. The researchers were also able to show that the amount of two proteins that are important for the connection between cells was reduced in twins, in both diseased and healthy persons. This could be one of the mechanisms that make the intestinal wall more permeable in Crohn’s disease.

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All these results of the researchers suggest that the barrier disorder is more a cause of Crohn’s disease than a consequence of the disease. The scientists’ thesis is also supported by animal studies. There, researchers have observed that defects such as these promote inflammation and not the other way around.

To better understand the role of genes, the researchers compared monozygotic twins with dizygotic twins. Since monozygotic twins hardly differ genetically, whereas fraternal twins differ by about 50 percent, the comparison of the siblings can help scientists to find out whether disorders in the intestinal barrier are genetically caused or whether they are caused by environmental factors.

The permeability of the intestinal wall was increased especially in healthy siblings of identical pairs of twins. The researchers, therefore, assume that the disturbance of the intestinal barrier could be largely genetically determined. Further studies will now have to clarify whether this is true. With just 15 pairs of twins, the generalizability of this study is quite small. Another step would be to find out which genes impair the barrier function of the intestine. More knowledge about the previously incurable intestinal disease would benefit many patients. In Germany alone, it is estimated that between 80,000 and 160,000 people are affected by Crohn’s disease.

This is part 41 of a series covering twin health provided by Paul Enck from the Tübingen University Hospital and science writer Nicole Simon. Further studies in twin research can be found at the TwinHealth website. Translation was done with the assistance of DeepL translator.

  1. Keita ÅV, Lindqvist CM, Öst Å, Magana CDL, Schoultz I, Halfvarson J. Gut Barrier Dysfunction-A Primary Defect in Twins with Crohn’s Disease Predominantly Caused by Genetic Predisposition. J Crohns Colitis. 2018 Nov 9;12(10):1200-1209.

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