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Proposed Crohn's model and treatment approach

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.
 
There is always hope and I am sure with time a solution will be found. What is interesting that we still don't know for certain what is causing the disease. Can an actual treatment be found without knowing the underlying cause? The anti-tnfs seem to work by addressing the resulting inflammation and only reduce symptoms.
 
I don't think there will be a single cure found in the same way as there is no cure for a cut on your arm. However, if you do the right things you may find that it's no longer a problem. Some people do get the right treatments and have remission for the rest of their lives, sometimes even after stopping treatment.
 
Note that the dominant mouse model of Crohn's involves having the mice drink water laced with dextran sodium sulfate (DSS), after which the mice have long-term intestinal inflammation.

I wonder if there are some components of modern human diets that act similarly.
 
once things get past a point.....its more like what doesnt antagonize it....aisle after aisle in what they call the "food" store....
and we can see things getting worse at a increasing rate....but....a little poison is fine it wont hurt.......our bodies are meant to filter out bad things etc etc.....
lying to us and poisoning us..........then giving us expensive drugs which dont address the actual causes......and being lied to by doctors in often cases too...hmm

wait, are we ranting? i didnt notice i started there ;P
 
Are there any scientists working on a cure for Crohn's disease?

I was terrified that Crohn's patients would be abandoned to the world and die a painful death.

We need hope
 

Scipio

Well-known member
Location
San Diego
Are there any scientists working on a cure for Crohn's disease?
Of course there are. Hundreds (thousands?) of scientists and physician/scientists are actively engaged in trying to figure out causes and cures for IBD. But unfortunately for us the disease is very complex and not easily understood. There is considerable evidence that "Crohn's disease" is actually several similar or overlapping diseases that may be caused (and hence treated) by several different factors. One thing that soon becomes apparent from reading this forum is that no two cases of Crohn's disease are exactly alike.

I remain hopeful of a true cure some day, but watching the progress in understanding and treating this disease over the past decade has convinced me to be very skeptical of anyone who claims to have solved Crohn's. IMO there is no one secret formula or special diet that is going to turn out to be the key to fixing Crohn's. Instead it's going to continue to be a long hard slog of adding up new bits of knowledge and figuring out new treatments. Or as the Emperor Hadrian put it in describing rebuilding Rome after a fire: "Brick by brick my fellow citizens. Brick by brick."
 
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Note that the dominant mouse model of Crohn's involves having the mice drink water laced with dextran sodium sulfate (DSS), after which the mice have long-term intestinal inflammation.

I wonder if there are some components of modern human diets that act similarly.
There are reports establishing relationships between our daily consumption of microplastics and IBD: https://pubmed.ncbi.nlm.nih.gov/34935363/

What is very puzzling to me is 1) Crohn's can cause problems outside of the GI system and 2) once you "get" it, it doesn't leave.
 
There are reports establishing relationships between our daily consumption of microplastics and IBD: https://pubmed.ncbi.nlm.nih.gov/34935363/

What is very puzzling to me is 1) Crohn's can cause problems outside of the GI system and 2) once you "get" it, it doesn't leave.
as i understand 1 is at least partially due to only starting to learn connections of brain and gut communications....i think i first heard of it in regards to GABA, which some people take even tho it wont cross the blood/brain barrier....simply because they noticed a correlation by the mere presence of it.

then we consider the correlations of autism and leaky gut or such.....the very idea of toxic elements leaking into the blood stream etc....it kind of makes a little sense at least i think....how that can start reaching places...

as i understand 2.....i think of it like adopting a dog that was "raised wrong".......you can teach it proper and the new training can work pretty consistently, but then one day for one random reason nobody can explain it cannot resist the bad behavior even if it knows its "wrong".

it seems there will always be a trace memory/fear in the dna once damage crosses a certain point.....which can also be passed thru generations it seems....the more bodily communications are confused, the more likely it will do the wrong thing etc....

i agree like this most likely is an overlap of several conditions at root makes sense to me....
2c
 
The microplastics-IBD relationship is very likely to not be causative but rather related to some other factors that are causative. eg foods that contain microplastics are also more processed and harder on the guts in general for other reasons.

This difficulty of interpretation is a problem that plagues most Crohn's research, nearly all nutrition research, a great deal of medical research, and most social science research.

Take the MAP-Crohn's connection as another example. MAP is found in many (most?) Crohn's patients but not in many healthy people. Many people believe that MAP causes Crohn's, and this is one piece of evidence in their favor. However, what if MAP is simply common in the environment and colonizes intestines whenever there's damage/inflammation? You'd see the same correlation between Crohn's and MAP, even if the inflammation actually comes before the MAP. That said, getting rid of MAP may still reduce inflammation even if some of the inflammation was already there when the MAP showed up.

Actually proving causation is hard.

I think the extraintestinal manifestations are most likely related to problems caused by the constant immune system activation and/or transport of bacteria or other intestinal contents that shouldn't be getting into the bloodstream to other parts of the body, due to a damaged intestinal barrier.

And finally, it's not really a life-long problem for everyone. There's a small minority of people who seem to get better indefinitely.
 
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