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- Nov 24, 2017
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Crohn's is characterized by inflammation in the intestines. The immune system is responding to some antigen in the region, and, since no autoimmunity has been discovered, it is probably the result of foreign material reaching areas that expose it to the immune response.
Theories of causation usually involve some kind of immune malfunction or pathogen, and many people are in one camp or the other. No specific pathogen has been fully proven, although AIEC or MAP may play a role in some cases. Specific immune malfunctions have been identified in a small percentage of cases, but these are not applicable to a large majority of patients.
Diet is generally believed to have some influence on the increase in Crohn's over time, but specifically how dietary changes have caused more Crohn's is unknown.
My theory is that Crohn's begins with some kind of physical damage to the tissues of the intestine. That damage may be caused by a combination of factors, including chemical damage (eg oxidation) from dietary components or infections.
For some reason, in Crohn's patients the damage doesn't heal. Perhaps it's because of an infection that takes too long to be cleared, or because of dietary habits that don't allow proper healing. Perhaps the real underlying problem is a defect of wound healing.
Nevertheless, the result is that Crohn's patients essentially have wounds in their intestines. The wounds mean that the intestinal barrier function is gone, and whatever is inside the intestines is now getting exposed to the immune system. The immune system responds to all of these antigens with inflammation.
What's inside the intestines? Essentially, poop and soon to be poop. Think about having a cut on your arm and rubbing that stuff on your arm multiple times every day. I think you'd get some swelling and probably some nasty infections.
So the Crohn's patient' s immune system is constantly battling all of the bacteria and other antigens that are always flowing over the region, and unfortunately the immune system isn't winning. Perhaps the immune reaction itself also begins to cause damage and prevent healing.
The underlying problem isn't really the inflammation--it's the tissue damage. The inflammation is the obvious and most troublesome result of the damage, but these things can get into a bad feedback loop.
Ok, so what does this mean for our approach to treating Crohn's? The goal of treatment should be heal or eliminate the tissue damage, which should also resolve the inflammation. These things go together, but they aren't exactly the same--it may be possible to stop all of the inflammation while not eliminating the damage or the source of the damage. This can be a semi-stable state, but solely getting rid of the inflammation is not the complete goal. (Sometimes, it may be good enough or the best current option).
Keeping this in mind, this is why I have referred a few times here to the usefulness of an MRI (or, potentially, an ultrasound) in assessing tissue damage. According to studies, intestinal wall thickness normalization is at least as good--and probably even better--an indication as mucosal healing in determining overall healing. If you still have intestinal thickening, you still have more healing to do.
Consider the various treatment options in the context of this theory:
Direct reduction of the inflammatory response: anti-tnfs (eg Humira), anti-il12/23 (eg Stelara), vedolizumab, other immune modulators. These directly reduce inflammation. Reduced inflammation can prevent further tissue damage and other complications, and it may also allow the intestines to heal.
Changing what's flowing through the gut: EEN, TPN, other special diets. These can promote healing by reducing damaging chemical content, bacteria, and other antigenic content of the guts, making the poop that's flowing over the wounds less of a problem.
Antibiotics: pathogens can invade damaged regions and perpetuate the problem. Infections in the wounded areas are common. Sometimes, getting rid of the pathogens can allow the guts an opportunity to heal.
Perhaps other options that improve healing would also be applicable, such as hyperbaric oxygen.
Surgery can remove particularly damaged areas, but it is critical to make sure the reattached areas heal properly. Note that Crohn's often comes back right at these reattachment points, where the tissue was cut and stitched back together.
Hopefully this is a useful way of thinking about Crohn's and how to approach treatment.
Theories of causation usually involve some kind of immune malfunction or pathogen, and many people are in one camp or the other. No specific pathogen has been fully proven, although AIEC or MAP may play a role in some cases. Specific immune malfunctions have been identified in a small percentage of cases, but these are not applicable to a large majority of patients.
Diet is generally believed to have some influence on the increase in Crohn's over time, but specifically how dietary changes have caused more Crohn's is unknown.
My theory is that Crohn's begins with some kind of physical damage to the tissues of the intestine. That damage may be caused by a combination of factors, including chemical damage (eg oxidation) from dietary components or infections.
For some reason, in Crohn's patients the damage doesn't heal. Perhaps it's because of an infection that takes too long to be cleared, or because of dietary habits that don't allow proper healing. Perhaps the real underlying problem is a defect of wound healing.
Nevertheless, the result is that Crohn's patients essentially have wounds in their intestines. The wounds mean that the intestinal barrier function is gone, and whatever is inside the intestines is now getting exposed to the immune system. The immune system responds to all of these antigens with inflammation.
What's inside the intestines? Essentially, poop and soon to be poop. Think about having a cut on your arm and rubbing that stuff on your arm multiple times every day. I think you'd get some swelling and probably some nasty infections.
So the Crohn's patient' s immune system is constantly battling all of the bacteria and other antigens that are always flowing over the region, and unfortunately the immune system isn't winning. Perhaps the immune reaction itself also begins to cause damage and prevent healing.
The underlying problem isn't really the inflammation--it's the tissue damage. The inflammation is the obvious and most troublesome result of the damage, but these things can get into a bad feedback loop.
Ok, so what does this mean for our approach to treating Crohn's? The goal of treatment should be heal or eliminate the tissue damage, which should also resolve the inflammation. These things go together, but they aren't exactly the same--it may be possible to stop all of the inflammation while not eliminating the damage or the source of the damage. This can be a semi-stable state, but solely getting rid of the inflammation is not the complete goal. (Sometimes, it may be good enough or the best current option).
Keeping this in mind, this is why I have referred a few times here to the usefulness of an MRI (or, potentially, an ultrasound) in assessing tissue damage. According to studies, intestinal wall thickness normalization is at least as good--and probably even better--an indication as mucosal healing in determining overall healing. If you still have intestinal thickening, you still have more healing to do.
Consider the various treatment options in the context of this theory:
Direct reduction of the inflammatory response: anti-tnfs (eg Humira), anti-il12/23 (eg Stelara), vedolizumab, other immune modulators. These directly reduce inflammation. Reduced inflammation can prevent further tissue damage and other complications, and it may also allow the intestines to heal.
Changing what's flowing through the gut: EEN, TPN, other special diets. These can promote healing by reducing damaging chemical content, bacteria, and other antigenic content of the guts, making the poop that's flowing over the wounds less of a problem.
Antibiotics: pathogens can invade damaged regions and perpetuate the problem. Infections in the wounded areas are common. Sometimes, getting rid of the pathogens can allow the guts an opportunity to heal.
Perhaps other options that improve healing would also be applicable, such as hyperbaric oxygen.
Surgery can remove particularly damaged areas, but it is critical to make sure the reattached areas heal properly. Note that Crohn's often comes back right at these reattachment points, where the tissue was cut and stitched back together.
Hopefully this is a useful way of thinking about Crohn's and how to approach treatment.
