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Why does inflammation happen?

Inflammation is an immue response to material that the body has identified as foreign. The elements necessary for inflammation to happen are:

1. Molecules which may be identified by the immune system as foreign,

2. The movement of those molecules into regions accessible to the immune system,

3. Recognition of those molecules by the immune system, and

4. The production of an inflammatory response by the immune system.

Let's examine each element. For element 1, molecules commonly found in human bodies generally do not get recognized as foreign. Autoimmune diseases do happen, but evidence indicates that Crohn's is not an autoimmune condition. See posts from @kiny on the elimination of inflammation after fecal stream diversion or filtering.

What foreign molecules do get identified by the immune system and provoke an immune response? Generally not simple and common molecules like sugars, but more complex molecules like proteins or cell membrane components from plants, other animals, bacteria, viruses, etc. Infections get identified by their bacterial or viral fragments, and allergic reactions are provoked by proteins or other foreign molecules which the immune system sees and responds to.

These molecules which may be identified as foreign are called antigens.

So, first off you need antigens (and note that some antigens provoke a much stronger response than others). Next, the antigens need to come into contact with the immune system. How does that happen? You need:

1. Physical contact with tissues, and
2. Sufficient diffusion of the antigens into the tissues to allow the immune system to detect the antigens.

I separate these two components in order to highlight a couple of issues. First, note that rubbing antigens on your skin will often not cause an immune response because your skin effectively blocks most substances from entering. Second, note that antigens have a much easier time getting in if your skin is wounded. Third, note that contact time matters. If the antigens do not have enough time to diffuse into the tissues, no immune response happens.

Consider one of the more common kinds of inflammation we are familiar with--gingivitis. Gingivitis happens when antigens stay in contact with gum tissues until inflammation occurs. The ordinary solution is brushing, flossing, and generally clearing away the plaque, which contains the antigens that are resulting in inflammation. It's important not to forget about the necessity of physical contact and diffusion.

This brings up the concept of intestinal permeability. A damaged intestine will have greater permeability, and higher permeability will reduce the amount of physical contact needed to provoke inflammation.

This also implicates the role of motility and stricturing or tight ileocecal valves. If the intestinal contents are backing up and not moving through fast enough, there may be opportunity for the tissues to receive direct chemical damage from the intestinal contents and for too many antigens to enter, resulting in an inflammatory response.

Many times I have seen posts saying that someone has a stricture and some inches of inflammation upstream of the stricture, but no inflammation downstream. The best explanation for this pattern is that backing up of intestinal contents itself is resulting in inflammation.

Sometimes inflammation also occurs downstream. Why might that be? My guess is that the microbiome plays a greater role in that case: once inflammation and damage get started, perhaps opportunistic infections get started and then spread easily downstream.

Note that LDN and vagal nerve stimulation may work for some people because it stimulates increased motility.

Going back to our list of elements necessary for inflammation, we have 3 and 4--recognition and production of an inflammatory response. These are what biologics and immune-suppressing treatments target. This can be very useful when the inflammation is spiraling out of control--when inflammation leads to damage which leads to increased permeability which leads to more inflammation. In some cases, perhaps unavoidable food or microbiome molecules are inevitably diffusing in and provoking a hypersensitive immune response, and the only thing you can do about that is to stop the immune hypersensitivity.

What does all this mean about how to reverse this and stop the inflammation?

1. Reduce antigen load via diet (eg EEN) and/or antibiotics

2. Reduce inflammation/immune hypersensitivity directly via biologics or medicines to stop the damage cascade

3. Promote motility via diet (eg get enough fluids), surgery to remove or open strictures, and/or medicines
These thoughts should not be interpreted to preclude a role for influence from the microbiota, specific foods, and/or immune deficiency in starting the Crohn's process and should be considered as complementary to other theories. The purpose here is to step back and look at things from first principles and kinetics.