Molecular and Phenotypic Characterization of Escherichia coli Associated with Granulomatous Colitis of Boxer Dogs

[Andersen007]

What you say makes complete sense to me. We are probably missing something crucial piece of the puzzle though. For example on a carnivore diet my calpro for 2 weeks remained exactly the same, 2000ish, although carbs and fiber was 0. Then when I introduced peanut butter and chestnuts, inflammation went down to 100ish. Also keto diet alone doesnt seem to do much for us Crohns patients. So thats why I feel like, yes starving pathogenic bacteria is a factor, but also there has to be a specific set of foods outside of this starving out carbs mechanism that is at play. And it makes sense to me that it would have to do something with the innocent part of our microbiome. But you brought a good example with FT-s that a lot of times a misbalance in the microbiome can actually increase the inflammation.

 

[asadmom]

What you say makes complete sense to me. We are probably missing something crucial piece of the puzzle though. For example on a carnivore diet my calpro for 2 weeks remained exactly the same, 2000ish, although carbs and fiber was 0. Then when I introduced peanut butter and chestnuts, inflammation went down to 100ish. Also keto diet alone doesnt seem to do much for us Crohns patients. So thats why I feel like, yes starving pathogenic bacteria is a factor, but also there has to be a specific set of foods outside of this starving out carbs mechanism that is at play. And it makes sense to me that it would have to do something with the innocent part of our microbiome. But you brought a good example with FT-s that a lot of times a misbalance in the microbiome can actually increase the inflammation.

What about the blood markers? did crp, sed rate stay elevated (assuming they were elevated prior to the diet) after 2 weeks of carnivore?

 

[Andersen007]

What about the blood markers? did crp, sed rate stay elevated (assuming they were elevated prior to the diet) after 2 weeks of carnivore?

My CRP and sed rate stay at rock bottom whatever happens to my Crohn’s, so it’s not very indicative in my case. Even at diagnosis it was super normal. I am a curious case though as EEN also makes things worse for me. I dont think carnivore made it worse, perhaps it did reset my gut enough that afterwards when I introduced some other foods that have fiber it was able to better react. But in itself it didnt move the inflammation in this timeframe and I continued to have very liquid - perhaps even more than before - stools with it. Looking back at the last 1 year, the 2 times I was able to get to solid 1-2x daily stools with 100-200ish calpro was when I was also having some type of fiber intake. Of course there are many compounding factors: for example I recently discovered with fairly high confidence that the nicotine product I am taking, snus (you put a pouch between your lip and teeth) seems to make things worse. And I would probably take slightly more of these on a no fiber diet because I feel less full etc. So, the adventure continues..

 

[J100]

I am apprehensive about microbiota studies because they are rarely uniform and often contradict each other.

Studies on the microbiota include lovely colored charts with bacterial phyla. But charts which I do not put much faith in.

The microbiota in the mouth is very different from that in the ileum, which is itself very different from that in the colon. Do the same study using a biopsy instead of a fecal sample, and the results will be radically different. Do that same study and change the diet in these patients, and the microbiota will have drastically changed within 24 hours. Put ruminants under pychological stress for 24 hours, and their microbiota will have drastically changed in response. Inflammation itself causes drastic changes in the microbiota, not just in crohn's disease, this is seen in intestinal TB and in response to foodborne infections.

It is impossible to find consistent and repeatable results, the microbiota quickly changes due to factors that are out of the control of these studies.

@kiny - Thanks for your response. The AIEC behind Crohns seems a logical and plausible explanation. If this is the cause, then why is it that the medication for Crohns keeps on going for the entire lifetime. Assuming that once the patient is in remission from Crohns, then the assumption is that the patient is not infected with AIEC anymore. However, the patient has to keep on taking medications such as methotrexate or other biologics etc.

 

[kiny]

Assuming that once the patient is in remission from Crohns, then the assumption is that the patient is not infected with AIEC anymore. However, the patient has to keep on taking medications such as methotrexate or other biologics etc.

Anti-inflammatories just mitigate inflammation, they don't kill bacteria. (you can argue anti-inflammatories might dampen inflammatory conditions conducive to prolifaration of certain bacteria that thrive in inflammatory environments, but now we're arguing semantics)

Tissue macrophage and dendritic cells that reside in intestinal tissue (lamina propria) release cytokine (TNF-a and IL-23) in response to antigen (bacterial / fungal). These cytokine cause rapid inflammation (it causes lymphocyte proliferation and differentiation, neutrophil migration etc).

The anti-inflammatories stop the inflammatory cascade by blocking those cytokine. But the anti-inflammatories do not stop the antigen, so the moment you stop the anti-inflammatories, the inflammation just comes immediately back. Anti-inflammatories will never cure crohn's disease, they don't solve the cause, they just mitigate the damage being done, because uncontrolled inflammation is tissue destructive.

 

[asadmom]

Propel just announced the recipient of their $100k research award is Promakhos Therapeutics https://www.promakhos.com/

Thoughts?

 

[kiny]

The current problem with chronic use of anti-inflammatories is also that patients will simply lose response.

These anti-inflammatories block certain inflammatory pathways, but the body (thankfully) has mulitple methods to mount an inflammatory response. So GI have to play Whac-a-mole with medication, because the body keeps mitigating the medication.

It's less than ideal. It's better than nothing, because nothing would lead to destructive inflammation in most patients, but anti-inflammatories are not a good long-term solution.

That's why EN is a good addition, because it work differently and there is no known loss-of-response to EN like there is to anti-inflammtories. There aren't reports of people where EN suddenly stops working, but there is plenty of evidence this happens with anti-inflammatories.

 

[asadmom]

Interview with the CEO: https://www.startuppirate.com/p/developing-therapies-for-chronic

 

[kiny]

I don't know what molecule it is or what they plan to do. But to put some data behind the "slow and fast immune sytem", because it's mentioned without context.

The innate immune response, namely the dendritic cells and macrophages in our intestines, react to "something" within hours.

The adaptive immune response, namely the lymphocyte response, comes later. We're talking days, around 1 to 5 days.

That's why I am a bit critical of "elimination diets" where people are told to identify food that causes issues themselves. Lymphocyte response can take several days, you can't just eat something and think that caused inflammation, the consumption of food and a noticeable immune reaction, is likely days apart. It's not like an allergy, crohn's disease involves mucosal damage, damage to the epithelial barrier, infiltration into tissue by bacteria/fungi or dietary antigen, innate response, T cell response, etc, this would take several days.

When Rutgeerts and Harper showed the immune response to the fecal stream, there were several days apart. I would need to look it up again, but it surely wasn't hours. The immune response in crohn's disease is slow, destructive and chronic, evoked by some kind of unidentified antigen.

 

[longzhiwu]

I don't know what molecule it is or what they plan to do. But to put some data behind the "slow and fast immune sytem", because it's mentioned without context.

The innate immune response, namely the dendritic cells and macrophages in our intestines, react to "something" within hours.

The adaptive immune response, namely the lymphocyte response, comes later. We're talking days, around 1 to 5 days.

That's why I am a bit critical of "elimination diets" where people are told to identify food that causes issues themselves. Lymphocyte response can take several days, you can't just eat something and think that caused inflammation, the consumption of food and a noticeable immune reaction, is likely days apart. It's not like an allergy, crohn's disease involves mucosal damage, damage to the epithelial barrier, infiltration into tissue by bacteria/fungi or dietary antigen, innate response, T cell response, etc, this would take several days.

When Rutgeerts and Harper showed the immune response to the fecal stream, there were several days apart. I would need to look it up again, but it surely wasn't hours. The immune response in crohn's disease is slow, destructive and chronic, evoked by some kind of unidentified antigen.

In February 2024 Propel a Cure awarded $100,000 to Promakhos Therapeutics for their innovative proposal, "Validating the Role of Mucosal Innate Immune Deficiency in Crohn’s Disease." Promakhos is a Boston-area incubator lab co-managed by Harvard University and Lab Central and housed in the Pagliuca Harvard Life Lab.

This team’s exciting project centers on the hypothesis that the mucosal innate immune response, and particularly the NOD2 pathway, is not activated correctly in Crohn’s patients. Based on their observations, up to 90 percent of patients with active disease – including those who do not have the NOD2 genetic mutation – have lower than normal levels of NOD2 molecules. This would appear to mean that the NOD2 is not functional and therefore impairs antimicrobial responses in Paneth cells, leading to defective bacterial clearance.

By reactivating the bacterial NOD2 signal, Promakhos believes that the defective communication between the gut microbes and the immune system could be restored in the majority of Crohn’s patients. Ultimately, they hope that their preclinical work that Propel a Cure will help fund and that will be completed in two years or less can pave the way for a curative, non-immunosuppressive oral treatment that can remediate faulty NOD2 signaling in the gut.

https://www.propelacure.org/researchprojects
————The treatment targeting NOD2 and Paneth cells sounds very great.Maybe we will clear AIEC in this way. What do you think of this project?

 

[kiny]

A substantial number of patients carry those NOD2 mutations. NOD2 competence is required for muramyl dipeptide recognition, used for bacterial detection. Anthony Segal also showed stunted neutrophil recruitment in crohn's disease, which would further dampen our innate immune response, I've posted the great paper before.

You can test for these genetic anomalies, but I would not do this, it helps nothing currently to know if you have them, and it will just cause people to worry. Keep in mind that many more people with these NOD2 anomalies do not have crohn's disease.

 

[J100]

A substantial number of patients carry those NOD2 mutations. NOD2 competence is required for muramyl dipeptide recognition, used for bacterial detection. Anthony Segal also showed stunted neutrophil recruitment in crohn's disease, which would further dampen our innate immune response, I've posted the great paper before.

You can test for these genetic anomalies, but I would not do this, it helps nothing currently to know if you have them, and it will just cause people to worry. Keep in mind that many more people with these NOD2 anomalies do not have crohn's disease.

I agree with it. Not every Crohn's patient has NOD2 anomaly.

 

[kiny]

I agree with it. Not every Crohn's patient has NOD2 anomaly.

Right. NOD2 and ATG16L1 anomalies serve as clues, clues that show us bacterial detection and bacterial clearance (see xenophagy) is very relevant to crohn's disease.

This would appear to mean that the NOD2 is not functional and therefore impairs antimicrobial responses in Paneth cells, leading to defective bacterial clearance.

Paneth cells are specific to the crypts of the small intestine, peyer's patches are ileal specific too, neither is found in the large intestine. I don't think crohn's collitis is the same disease as ileal crohn's disease. People get annoyed sometimes when I point this out, but it's possible they have little to do with one another, and this likely explains the different responses to medication and EN. Hopefully treatment can solve both.

 

[longzhiwu]

Right. NOD2 and ATG16L1 anomalies serve as clues, clues that show us bacterial detection and bacterial clearance (see xenophagy) is very relevant to crohn's disease.



Paneth cells are specific to the crypts of the small intestine, peyer's patches are ileal specific too, neither is found in the large intestine. I don't think crohn's collitis is the same disease as ileal crohn's disease. People get annoyed sometimes when I point this out, but it's possible they have little to do with one another, and this likely explains the different responses to medication and EN. Hopefully treatment can solve both.

Maybe the people without Crohn's disease do not have intestinal colonization of AIEC. If we can impair antimicrobial responses in Paneth cells, I think it will be helpful for us to clear AIEC or other pathogenic bacteria.

 

[kiny]

Something is going on in the tissue of crohn's disease patients that prevents complete bacterial or fungal clearance. Phagocytes are continuously being activated by "something" that is able to evade and circumvent the immune system, preventing mucosal and gut homeostasis. So we either need to remove the offending antigen, or make the immune response competent enough so it can do so itself.

 

[kiny]

We don't have all the dots, but we have enough to take a shot.

-disease onset is often linked to foodborne infection, which would cause substantial tissue damage allowing bacterial entry. Fevers, night sweats, throwing up, are all disease onset symptoms.
-compromised innate immune response results in lack of bacterial/fungal clearance, some genetic anomalies make this worse
-crohn's disease presents itself in areas with high bacterial load, ileal, colonic and oral cavity, manifestations in other parts of the GI tracts with low bacterial load are extremely rare, and likely unrelated to crohn's disease
-pathogenic bacteria and fungi in tissue are involved, preventing resolution of inflammation and compromising the epithelial barrier
-the patchy nature of inflammation and granuloma rule out a direct response to the microbiome
-however, the fecal stream high in bacterial and fungal load causes lumen content to enter tissue
-if you introduce a fecal stream high in bacterial load, like a fecal transplant, inflammation shoots up
-removal or diversion of the fecal stream causes resolution of inflammation
-if you take EN, the fecal stream, bowel movements and bacterial load decrease, causing resolution of inflammation and healing, very low grade inflammation persists in some patients, likely reflecting unresolved antigen residing in tissue
-probiotics don't help crohn's disease, why would they
-oral iron supplementation likely increases bacterial load and result in inflammation in mouse models, IV should be used to correct iron defficiency instead
-anything that helps the immune system to resolve bacterial clearance more competently, like supportive vitamin D, tends to improve disease status

 

[Scipio]

I agree with it. Not every Crohn's patient has NOD2 anomaly.

Correct. I have neither NOD2 nor ATG16L1 allelic abnormalities. But I do have ileal Crohn's disease.

 

[kiny]

Posted it years ago, but still relevant. Marcel Behr is a lovely person.

 

[kiny]

Very early crohn's disease involves tiny spots of inflammation, I posted many pictures of them. They appear both in the mouth and ileally they appear on peyer's patches. But it doesn't look like an immune response to the microbiome to me.

The body builds up mucosal tolerance to commensal bacteria, even during change. Lumen bacterial populations are generally kept at bay by a mobile mucosal barrier, and bacteria that do brush up against tissue are tolerated without T-cell response. The relationship is symbiotic.

However, peyer's patches are not covered by mucosa, and commensals interact with the immune sytem through the little dome structures, called M cells. But still, these commensals are dealt with "gently" by secretion of IgA and suppressed T cell response.

However, when a pathogen like AIEC, Klebsiella or fungi, causes deep transmural inflammation and tissue damage, lumen content is suddenly no longer kept at bay, and fecal matter high in bacterial load will enter tissue. EN likely brings relief by limiting this fecal matter from interacting with the mucosal immune system. The tolerance towards commensals has not changed in crohn's disease imo, but lumen content will inadvertently interact with the mucosal immune system during inflammation.

I wonder if there are any studies that compared EN to liquid diet. I would like to know if the liquid form of EN might limit it's contact with the epithelial barrier in the ileum. During inflammation, all sorts of particles and lumen content would enter tissue, including food proteins that are generally not fully absorbed, commensal bacteria, etc.

 

[asadmom]

I just learned today that there is a such thing called autoimmune hepatitis. The doctor said that these patients take different medications to suppress their immune systems. The doctor also said for people with Crohn's who also have autoimmune hepatitis, the cause is not Crohn's is attacking the liver as well. It's more of there is a "core" immune dysfunction in the background that drives and manifests the inflammation at different target organs.

Thoughts?

 

[longzhiwu]

Very early crohn's disease involves tiny spots of inflammation, I posted many pictures of them. They appear both in the mouth and ileally they appear on peyer's patches. But it doesn't look like an immune response to the microbiome to me.

The body builds up mucosal tolerance to commensal bacteria, even during change. Lumen bacterial populations are generally kept at bay by a mobile mucosal barrier, and bacteria that do brush up against tissue are tolerated without T-cell response. The relationship is symbiotic.

However, peyer's patches are not covered by mucosa, and commensals interact with the immune sytem through the little dome structures, called M cells. But still, these commensals are dealt with "gently" by secretion of IgA and suppressed T cell response.

However, when a pathogen like AIEC, Klebsiella or fungi, causes deep transmural inflammation and tissue damage, lumen content is suddenly no longer kept at bay, and fecal matter high in bacterial load will enter tissue. EN likely brings relief by limiting this fecal matter from interacting with the mucosal immune system. The tolerance towards commensals has not changed in crohn's disease imo, but lumen content will inadvertently interact with the mucosal immune system during inflammation.

I wonder if there are any studies that compared EN to liquid diet. I would like to know if the liquid form of EN might limit it's contact with the epithelial barrier in the ileum. During inflammation, all sorts of particles and lumen content would enter tissue, including food proteins that are generally not fully absorbed, commensal bacteria, etc.

AIEC seems to be a trigger that starts a series of problems in the intestinal, or a bad guy that kicks the door and other things enter the house.Therefore, if we want to repair the house, we must repair the door and eliminate AIEC at first.

 

[kiny]

It's more of there is a "core" immune dysfunction in the background that drives and manifests the inflammation at different target organs.

Idk. Innate immune dysfunction and NOD2 anomalies are not just seen in crohn's disease, they are seen in the syndrome of Blau and in CGD (chronic granulomatous disease). Not surprisingly, many (relative to the normal populatioN) people with CGD develop crohn's disease. But what is surprising is that there have been some cases where this resolved in CGD.

 

[kiny]

AIEC seems to be a trigger that starts a series of problems in the intestinal, or a bad guy that kicks the door and other things enter the house.Therefore, if we want to repair the house, we must repair the door and eliminate AIEC at first.

At 4 weeks people who go on EN usually have their calprotectin drop from 1000+ to <200. What I find surprising is that in many patients this inflammation doesn't drop below 100, it sort of hovers between 100-200. People are technically in remission, but some type of low-grade inflammation seems to persist.

Our immune system is likely capable of eliminating AIEC to some degree, and other pathogns residing in tissue, if conditions were more sterile. I assume it gets overwhelmed by the addition of lumen content that will enter tissue. It's possible that the low grade inflammation seen in patients on EN, is simply the sign of a resident tissue pathogen that we have trouble clearing, and that the actual inflammatory cascade is caused by the addition of lumen content.

 

[kiny]

The intersting thing about the oral aphthous uclers in crohn's disease, is that it comes and goes in patients. Mucosal tolerance is shared in the body, so are some bacteria in the intestine and oral cavity, there is a difference but also some overlap.

When lumen content high in bacterial load enters intestinal tissue, it is not that surprising that you would see a temporary reaction in the oral cavity, against the same bacteria brushing against the mucosal barrier in the mouth.

 

[kiny]

The fact oral ulcers always seem to resolve on their own in people with crohn's disease, is another reason I do not believe an immune response against commensals or "the microbiome" is actually persistent. I do not see this as loss-of-tolerance at all. I think it is simply lumen content entering tissue under inflammatory conditions, especially through the fecal stream, EN is likely able to mitigate this.

 

[kiny]

That the fecal stream maintains inflammation is very well documented, Harper, Rutgeerts, etc. All studies from the 80s and 90s, but still some of the best clues we have. We also know IV feeding leads to significant drops in inflammation.

 

[J100]

If you're wondering what causes the actual damage in crohn's disease, it's the inflammation. To be more specific, it is oxidative stress.

When the innate immune system and macrophages try to kill the bacteria, they use low pH and enzymes to do it. One of those enzymes is phagocyte oxidase, this is what causes the oxidative stress, this is what causes tissue damage in crohn's disease.

The enzymes used to kill bacteria also damage tissue. And because the immune system is unable to kill those bacteria, the intestine is in a chronic state of stress and inflammation.

To stop the inflammation people use anti-inflammatories which stops the release of those enzymes, it heals the intestine, but it doesn't fix the problem of course, the bacteria are still there. The moment you stop anti-inflammatories, the inflammation restarts. The only way to stop it is to do something about those bacteria.

In many infections, anti-inflammatories are actually used, to prevent too much tissue damage.

Anti-inflammatories are used during COVID too.

What happens in crohn's disease is what also happens in chronic granulomatous disease, which is very closely related to crohn's disease. Many people with granulomatous disease develop crohn's disease.

This entire thread has been very informative. It explains why Crohn's is a progressive disease and why the body finds a way around the medications. And because of this reason, I despair because the medical science is nowhere near closer to a cure.

 

[my little penguin]

@J100
Understand there may not be a cure but there are meds /diet combos which keep the intestine pink & healthy for most for many years with little impact on day to day life.
Cure would be great but there are many diseases without cures that have treatments .
My kiddo was dx with more than a few diseases and is an adult (13 plus years of disease now ) living good life .
The meds stopped his disease progression .
No scar tissue ,no fistulas , no ulcers nada just pink healthy tissue

 

[Scipio]

There is definitely no cure for Crohn's in sight. But thanks to the arsenal of modern medications, Crohn's has joined the ranks of diseases such as high blood pressure, diabetes, lupus, HIV, and some forms of cancer that can't be cured but in most cases can be successfully managed to the point that patients live a more-or-less normal life for many years, perhaps for a lifetime.

 

[kiny]

Antioxidants are able to mitigate some of the tissue damage from the oxidative response of macrophages. Interestingly, people with crohn's disease tend to be deficient in some of of those antioxidants.

Inflammation in the ileum not only damages intestinal tissue, it leads to malabsorption, which prevents proper uptake of some major antioxidants like vitamin C. Not surprisingly, Vitamin C deficiency is common among crohn's diseae patients. I don't think multivitamins to correct such defficiencies used in some studies are a great solution, because they contain other substances like excess iron, which are known to worsen intestinal inflammation in mouse models. EN high in antioxidants might be correcting some of those antioxidant shortages.

 

[kiny]

As this study rightly points out, the fecal stream drives inflammation.

However, this is one of several studies showing there was no difference between the microbiota of inflamed and non-inflamed tissue.

This suggests dysbiosis is a consequence of inflammation, not a cause.

If the inflammation was caused by changes in the microbiota, one would expect the whole intestine to be inflamed, and one would not expect pockets of inflammation, and one would certainly not expect the same microbiota at sites of non-inflamed healthy tissue.

There is no proof the inflammation is caused by a change in the microbiota in crohn's disease patients and there is no proof trying to modify this microbiota is helpful. Both probiotics and fecal transplants have spectacularly failed and caused inflammation to worsen in several studies, likely due to a forced increase in bacterial load.

EN is able to induce remission in 80% of patients, even though EN completely lacks fiber, causes further dysbiosis and decreases bacterial diversity. But maybe more importantly, EN decreases bacterial and fungal load and is very effective at treating SIBO.

What we do know is that the fecal stream high in bacterial, fungal load and food particles, results in inflammation, and when this effluent is filtered, inflammation does not occur. We also know that an increased presence of several pathobiont and pathogenic species of E Coli is found in inflamed tissue.

 

[kiny]

Note that bacteria/fungi are a prerequisite to maintain crohn's disease, as inflammation would not exist in a sterile environment.

This also puts into question the wisdom of some GI who performed fecal transplants to treat crohn's disease, and were somehow shocked it exacerbated inflammation.

And it puts into question the wisdom of all the dieticians and doctors promoting "feeding healthy gut bacteria" with prebiotics, probiotics, fiber, etc. Until their patients develop SIBO. Animals with transient microbiomes and low bacterial load don't have nearly the number of intestinal diseases humans do.

 

[Andersen007]

What we do know is that the fecal stream high in bacterial, fungal load and food particles, results in inflammation, and when this effluent is filtered, inflammation does not occur.

wouldn't this be super easy to prove? as in, we know Crohn's occurs in the TI and large bowel - so why not just make a (temporary) surgery of cutting the small intestine before the terminal ileum, and connect it to a stoma bag? If your theory is correct, that should essentially cure Crohn's disease as there is no fecal stream that ever makes it to the TI or downwards right? This is also why I am sceptical - if there would be such a clean cut way to cure this, I am guessing we would have heard about it?

 

[kiny]

It's posted above.

https://crohnsforum.com/threads/mol...litis-of-boxer-dogs.85825/page-2#post-1053657

"The enemy is in the fecal stream" wrote Balfour Sartor.

IV feeding is highly effective in inducing remission, but rarely done due to risks of infection.

The offending agent has to be larger than the ultrafiltrate used by Rutgeerts and Harper. Bacteria, Fungi (yeasts) or large dietary particles. A recent Nature study indicated T cell response directed at dietary yeasts.

Avoiding dietary yeast is now a reasonble recommendation, especially in ASCA+ patients.

 

[kiny]

The small lesions in early onset crohn's disease look a lot like the aphthous ulcers seen in the mouths of chrohn's disease patients. They heal in the mouth, but develop into deeper transmural inflammation in the intestine. That might just be because of the much higher bacterial load in the intestine. The microbiome likely exacerbates those lesions, but is very unlikely to be the cause.

 

[longzhiwu]

It's posted above.

https://crohnsforum.com/threads/mol...litis-of-boxer-dogs.85825/page-2#post-1053657

"The enemy is in the fecal stream" wrote Balfour Sartor.

IV feeding is highly effective in inducing remission, but rarely done due to risks of infection.

The offending agent has to be larger than the ultrafiltrate used by Rutgeerts and Harper. Bacteria, Fungi (yeasts) or large dietary particles. A recent Nature study indicated T cell response directed at dietary yeasts.

Avoiding dietary yeast is now a reasonble recommendation, especially in ASCA+ patients.

This clinical trial may give us an answer about fungus in Crohn disease. According to the study, it will be completed in March.

https://classic.clinicaltrials.gov/...rm=itraconazole+and+terbinafine&draw=2&rank=1

 

[kiny]

NOD2 mutations impact both bacterial, but also fungal clearance. Chitin is a component of the fungal cell wall, and recognition of this component seems to be NOD2-dependent.

Around 50% of CD patients in the West have at least 1 such NOD2 mutation. The encouraging aspect is that far more people with one or more NOD2 mutations do not have crohn's disease. NOD2 mutation are common.

Another encouranging fact is that people with crohn's disease seem to have little issue clearing fungal and bacterial infections in general, even with these NOD2 muations, the immune reaction in crohn's disease seems comptent, it likely just gets overwhelmed in the intestine which gets bombared daily with antigen. The innate immune response in crohn's disease is lot more competent compared to diseases considered primary immune defficiencies.

So a reversal of disease state, should certainly be possible, with the right interventions that decrease fungal and bacterial load, like EN, anti-fungal and anti-bacterial treatments.

In the meantime, I would be extremely careful of treatments that increase antigen load on the immune system, fecal transplants and probiotics have not shown any improvement, and have shown many times their potential for harm.

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[my little penguin]

I think probiotics vary greatly
Most do not affect crohns in a positive manner instead make things worse .
There are some exceptions.
My child is one of those .
His probiotics are Gi prescribed so not over the counter and for whatever reason improve his crohns symptoms in the rectum .
When he stops them or was not them he got worse .
His crohns is very atypical and does not follow any “normal “ crohns patterns per Gi.
So remember there are exceptions and discuss with your doc based on your history.

studies are great but I know from talking to my child Gi any weird presentations are specifically excluded from studies so as to not provide confusing results . This imo muddies the waters for a lot folks with crohns since studies are not a complete picture .

 

[J100]

As this study rightly points out, the fecal stream drives inflammation.

However, this is one of several studies showing there was no difference between the microbiota of inflamed and non-inflamed tissue.

This suggests dysbiosis is a consequence of inflammation, not a cause.

If the inflammation was caused by changes in the microbiota, one would expect the whole intestine to be inflamed, and one would not expect pockets of inflammation, and one would certainly not expect the same microbiota at sites of non-inflamed healthy tissue.

There is no proof the inflammation is caused by a change in the microbiota in crohn's disease patients and there is no proof trying to modify this microbiota is helpful. Both probiotics and fecal transplants have spectacularly failed and caused inflammation to worsen in several studies, likely due to a forced increase in bacterial load.

EN is able to induce remission in 80% of patients, even though EN completely lacks fiber, causes further dysbiosis and decreases bacterial diversity. But maybe more importantly, EN decreases bacterial and fungal load and is very effective at treating SIBO.

What we do know is that the fecal stream high in bacterial, fungal load and food particles, results in inflammation, and when this effluent is filtered, inflammation does not occur. We also know that an increased presence of several pathobiont and pathogenic species of E Coli is found in inflamed tissue.

View attachment 4798

@kiny - Actually Stanford university had done some clinical trials on FMT in pediatric patients with Crohn's disease. I don't have a link to the study now. However, the trials were stopped because the outcomes were slightly worse. Likewise Boston Children's hospital doesn't do FMT in Crohn's disease. I believe they had a trial which they have stopped.

 

[longzhiwu]

@kiny - Actually Stanford university had done some clinical trials on FMT in pediatric patients with Crohn's disease. I don't have a link to the study now. However, the trials were stopped because the outcomes were slightly worse. Likewise Boston Children's hospital doesn't do FMT in Crohn's disease. I believe they had a trial which they have stopped.

This is a pilot study of FMT on CD patients with AIEC.

https://classic.clinicaltrials.gov/ct2/show/NCT05611866?term=AIEC&draw=2&rank=1
The clinical trial is very interesting and I have never heared before.This team has been studying AIEC for a long time. In one of their studies, they consider that the presence of AIEC impeded restoration of normal gut microbiota. Perhaps AIEC is the reason that prevents FMT from from repairing the intestine.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8632309/
On this basis, the trial of FMT on CD patients with AIEC was designed and carried out. I don't know the difference between this FMT and other FMTs. But I think the results of the clinical trial will be very helpful for us.

 

[J100]

@kiny - Is it possible that AIEC can still be there in pasteurized milk? My son was diagnosed around the age of 1.5 years when his primary diet was milk.

 

[cheka]

People will often say 'it's genetic, my dad, uncle, had it'.

There is an undeniable genetic predisposition, but you aren't born with this disease, there are tons of people who also have these genetic anomalies who do not have crohn's disease.

People live for years without this disease, and within days, they suddenly develop the disease, high fevers, night sweats and intestinal inflammation.

There was a (rather acute) event in life that brought forth this disease.

There has to have been some kind of infection. The infection has to be common enough to explain the sheer prevalence of the disease. Foodborne infections that cause substantial damage to the intestinal lining enabling AIEC to enter tissue are a reasonable explanation.

gut dysbiosis leads to bacterial translocation from the large intestine to the small intestine and then infection/inflammation/leaky gut in the small intestine. they call it 'sibo'. medical pushes pharma antibiotics for this. but that blunt tool harms the good guys and the bad guys - not ideal. there are gentler/safer strategies than pharma antibiotics for sibo.

besides the translocation there is another cause -- low stomach acid, letting pathogens get through. the super low ph of the stomach is supposed to kill the bad guys before they get into the small intestine. low acid can let the bad guys in

what causes gut dysbiosis? it's what we put in our mouths -- wrong foods, meds, booze, etc

known things that wreck the gut

1. oils - fried or in junk foods
2. nsaid pain relievers - literally eat holes in your gut
3. fake sugars -- all of them, including stevia harm the gut bacteria
4. booze
5. breads are a problem for a lot of people

eliminate these when you decide to work on your gut dysbiosis and leaky gut

 

[cheka]

@kiny - A question - It seems that AIEC can cause Crohn's in a very short span of time. However, I am reminded of a study which was done which showed that the gut microbiome changes in patients years before the onset of Crohn's. I have pasted the link though I am not sure if this is correct link. What are your views on it.

https://www.gastrojournal.org/article/S0016-5085(23)00805-3/fulltext

bingo! i'm finding lots of new research that confirms your hunch. microbiome changes are the wellspring of all of it. many MANY diseases have the same cause. see the hottest new science papers/studies/trials in the 'research' subforum. they are starting to figure it out. slooooooowly