Crohn’s Disease and Ulcerative Colitis affect millions of people worldwide — but why? What causes all that misery? The truth is… nobody really knows.
CD and UC are forms of ‘inflammatory bowel disease’ — IBD for short. There are other diseases, too, that count as IBD, but those are the main two. And, in fact, Crohn’s and UC are probably part of a cluster of diseases that look similar but have slightly different causes — on which more in a moment.
Obviously, if we don’t even know for sure what these diseases are, it is hard to say for sure what causes them. The best science at this point tells us they are caused by in part by genetic factors and in part environmental triggers — but nobody is sure what those causes are, exactly.
Many doctors will tell you genetics explains about half of IBD — but that actually doesn’t tell us much.
We know IBD is genetic because it tends to run in families, but we don’t know exactly how that happens (I’ll write more on heredity in a later post). We do know that IBD is not caused by a single genetic flaw, like cystic fibrosis or Huntington’s.
IBD is complex and polygenic — complex means it does not follow simple genetic patterns like eye color or Huntington’s, and polygenic means it involves several genes. All total, some 163 genes have been linked to IBD (there are about 200,000 genes in human DNA total). That doesn’t mean you need all 163 genes, or that there are 163 different kinds of IBD. For starters, some of these genes will turn out to have nothing to do with IBD, after more research.
For those genes that have a clear link to IBD, it’s probably the case that you need a few different genes, and that there’s some overlap in how they lead to disease. The genes thought to be responsible for IBD control functions like “microbe recognition, lymphocyte activation, cytokine signaling, and intestinal epithelial defense”; there is a lot of overlap in the genetics between UC and CD, and also between IBD and celiac disease.
As scientists and physicians learn more about IBD genetics, the differing types of IBD will become more distinct from one another — which will also help us understand why some medicines work great for one patient but fail for another. If you have Crohn’s or UC, it’s possible that you will see that diagnosis renamed in the next decade or two, as science learns more about what’s wrong with us.
On the one hand, we know some genes (really, errors in those genes) control various parts of the immune response that drives IBD; on the other hand, probably not everyone with those bad genes will get the disease.
The other part of the disease is environmental factors, which means anything not part of the body itself. Again — this does not tell us all that much.
Unfortunately, the science on environmental factors is not nearly as settled as that for genetics. In fact, there are too many possible environmental factors to cover here, but this paper is a good summary of recent research. I’ll cover a few of the major candidates here.
Dysbiosis : this translate to ‘messed-up biome’. Your microbiome is the community of microbes living in your gut and elsewhere in your body, most of which help you digest food or resist other infections, but some of which can be harmful if not held in check by your body or good organisms. In this view of IBD, the environmental factor is an imbalance in the microbiome, which the body can’t handle properly. It may be that antibiotics or some other agent triggers the imbalance initially, but it could also be that it just happens for some people, with no trigger.
Infectious organism : some infectious diseases have been associated with occurrence of IBD, so it may be the case that getting a specific pathogen can trigger the disease in someone who is already susceptible. This article (again) mentions several possible culprits, which include bacteria in the Listeria, Escheria, Salmonella, and other families. Also mentioned is the fungus Candida albicans — which also causes yeast infections and thrush. In this theory, infection by one of these bugs triggers a reaction that runs out of control, leading to chronic inflammation in the gut and elsewhere in the body.
One of the most talked-about possible bacteria associated with IBD — especially Crohn’s — is called Mycobacterium avium paratuberculosis, or MAP for short. A recent study by the British government [pdf] found mixed evidence for MAP in Crohn’s, but allows for the possibility that it might be to blame for some cases of the disease. This is still more evidence that IBD includes more than one or two specific diseases.
Hygiene hypothesis : a closely-related theory is that IBD is caused when an immune system runs amok from not fighting off bad organisms. According to the hygiene hypothesis, our immune systems have co-evolved with many, many different diseases and parasites; those infections help train the immune system to not to attack the rest of the body. This is theory behind treatments like TSO (pig whipworms): by introducing a parasite, the immune system is re-trained to act properly.
Only recently have industrialized countries succeeded in wiping these diseases out. Now, however, autoimmune disorders like IBD are on the rise in those countries. Children who move from developing countries to industrialized countries are much more likely to develop IBD than their peers who remain in the developing world.
Causes and Consequences
We know inflammatory bowel disease is part genetic, part environmental. We know that many genes are associated with IBD, and some specifically with one form or another — but we still don’t know what genes are responsible, whether they are associated with specific triggers, or even how many forms of IBD there really are.
Obviously, this is a crucial area for more research. The good news is that it’s getting done. Advances in genetic analysis are making that research easier and easier, knowledge of the immune system and its function is growing exponentially, and our emerging understanding of the microbiome promises exciting breakthroughs in the near- to mid-term. Crohnology members are part of that research — through clinical trials and other studies.
Of course, the hope is that by better understanding the causes of the disease, we can better understand how to prevent and treat it. That becomes more true every day, but in the meantime we still don’t really know exactly what causes inflammatory bowel disease.