Watch Dr. Brian Coombes discuss his research into the possible link between Adherent Invasive E-coli and Crohn’s

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Thanks, he's a very nice person.

Foodborne infections are very common in the West, they would leave the intestine permeable and allow for entry of AIEC into deeper tissue.

Early symptoms of crohn's disease include inflammation of peyer's patches, night sweats, vomiting. An acute primary infection is likely the trigger that allows AIEC to become a persistent secondary infection.

The clustering of crohn's disease cases that Van Kruiningen discovered match that of localised infection of the food supply with a foodborne pathogen, salmonella and campylobactor infections are very common in the West. By the time patients are diagnosed with crohn's disease, weeks would have passed and that primary infection will have been overcome.
 
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Due to the nature and prevalence of crohn's disease, the initial trigger would have to be widespread within Western society, be able to cluster to explain crohn's clustering, and cause ileal specific enteritis. Salmonella and Campylobacter do this on a large scale in Western society.

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Pretty cool guy, and they seemed to cover a lot of the best questions. He basically said anything that can damage the microbiome could cause crohn's disease. My thoughts are, so then how do we restore a damaged microbiome? a Fecal Microbiota Transplant!!! If you weren't aware yet, in my initial post of my fecal transplant thread i posted a report of a women being cured of crohn's disease with a Fecal Transplant in 2014 by Dr. Thomas J. Borody, in 2014 it was already determined she may have been cured for 12 years, and i recall another follow up a few years saying she still had no symptoms.


"When Professor Borody offered this chance of a cure I thought: what if it works?" she said.
"They put a nasal tube down into my small intestine. I had three donors - about 950 mils - and all up it took about five hours."
She says she felt better almost immediately and over several months her condition steadily improved.
"Eleven months after having the stool transplant I had another colonoscopy to see what it looked like," she said.
"I remember I was waking up from the anaesthetic and I heard Professor Borody say if he hadn't known I'd had Crohn's he wouldn't have believed it. I was so happy."Ms Heskett's colon has been healthy for 12 years with no sign of the Crohn's infection that had kept her housebound for years."
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SOURCE: Doctor Tom Borody claims faecal transplants curing incurable diseases like Crohn's
 
You see what I find interesting is if you have surgery cut the disease out, and a few inches each side extra.

After the procedure the patient feels in remission better than ever, can eat anything.

Well after recovering from surgery.

Then on average 2 years later the disease comes back.

So why is it coming back in the same location even when you cut it out, on an average of two years after if I recall?

This would suggest that there are rougue cells or genes maybe ?
 
wildbill_52280 said:
Pretty cool guy, and they seemed to cover a lot of the best questions. He basically said anything that can damage the microbiome could cause crohn's disease. My thoughts are, so then how do we restore a damaged microbiome? a Fecal Microbiota Transplant!!! If you weren't aware yet, in my initial post of my fecal transplant thread i posted a report of a women being cured of crohn's disease with a Fecal Transplant in 2014 by Dr. Thomas J. Borody, in 2014 it was already determined she may have been cured for 12 years, and i recall another follow up a few years saying she still had no symptoms.



SOURCE: Doctor Tom Borody claims faecal transplants curing incurable diseases like Crohn's
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I agree with you, Wildbill, of the potential of FMT, though this report from Borody is anecdotal. It is unfortunate that more robust random controlled studies have not been done on Crohn's patients. We need to control for disease activity, where it is located, the existing microbiota, the number of treatments, the donors' microbiota, the meds/vitamins/diet of both recipient and donor, etc., and of course the number of participants. It would also be helpful to know how long responders remain in remission. If I would just win the lottery, I'd seriously support such a study! :)
 
westernbuddy said:
You see what I find interesting is if you have surgery cut the disease out, and a few inches each side extra.

Then on average 2 years later the disease comes back.

So why is it coming back in the same location even when you cut it out, on an average of two years after if I recall?
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https://www.thelancet.com/journals/lancet/article/PII0140-6736(91)90663-A/fulltext

Rutgeerts his study showed that in people who had surgery, the disease returns just after a few months in other parts of the intestine that was previously unaffected, in the form of aphthous lesions.

Take note that these aphthous lesions are also the first endoscopic signs of crohn's disease when the disease is detected early.
"Aphthous lesions recur in the neoterminal ileum within the first few months after curative resection of the distal ileum in patients with Crohn's disease. These lesions do not originate from microscopic disease that is already present at the time of surgery."
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However, any part of the intestine that is diverted from coming into contact with the fecal stream remains completely free of inflammation.
None of the 5 patients had endoscopic lesions in the neoterminal ileum after six months of exclusion and biopsies did not show inflammatory changes characteristic of Crohn's disease. Our findings strongly support the view that recurrence of Crohn's disease in the neoterminal ileum after curative ileal resection is dependent on faecal stream.
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Rutgeerts and Harper then did follow up studies on this and started filtering the fecal stream with a ultrafiltrate, 22nm, which is small enough to filter out all the bacteria and fungi. Intestinal tissue of crohn's disease patients that comes into contact with that filtered effluent, show no inflammation at all. Neither in the ileum or colon.

The only explanation is that bacteria (or fungi) are causing the disease. Just like Dr. Coombes said, the initiation of the disease and maintainence requires a bacterial environment. Put it another way, in a world without bacteria, crohn's disease would not exist.

Giving chronic oral antibiotics might work very well initially, but eventually you create an environment where pathogenic bacteria become resistant and you now have a worse situation than you did before.

So you need a targeted approach to go after the pathogenic bacteria causing issues, like AIEC, and you leave the rest of the bacteria alone. Bacteriophages or FimH blockers for example.

https://pubmed.ncbi.nlm.nih.gov/9453485/
https://gut.bmj.com/content/gutjnl/26/3/279.full.pdf
 
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When Coombes talks about that initial trigger of a foodborne infection that might have allowed AIEC to gain the upper hand. It is what Antony Segal suspects too.

Why and how we initially came down with crohn's will not lead to better treatment in the here and now. It is not our fight. Making sure meat is properly cooked and not drinking unpasteurized milk is about all one can expect to do to avoid foodborne infections.
 
The 1985 article, that is worrying, as its almost 40 years old, and it mentions crohns has been researched extensively for a long time and yet they have not got anywhere.

That article could be dated 2021.

I get what your saying, you don't need to know why it rains to stop getting wet?

However might we know in advance how the rain is produced we can stop people getting the disease in the first place? But there again if we can treat it effectively and safely it does not matter.

I think I'd feel better about any medication I was takeing if I knew the cause for the reason I was taking it.
 
Tangentially related, here's my personal theory of Crohn’s, which I think best explains all the evidence.

My guess is that it all starts with some kind of physical damage, eg from an infection, food digestion gone wrong (eg something about diet resulting in chemical damage in a particular region), or even a traumatic accident. Most people can heal from occasional damage like this, but in Crohn's patients it doesn't heal.

Maybe it doesn't heal because the damage is too extensive to begin with, because the damage is repeated too many times, because of some innate defect in wound healing, or maybe because a bacteria like AIEC gets in and causes a chronic infection that prevents healing (reminiscent of peptic ulcers).

Notice that the best mouse model of Crohn’s involves giving mice a chemical (DSS) which damages their intestines and starts off a chronic inflammatory response.

A damaged intestine plus the fecal stream results in exposure of the immune system to antigens, which responds with inflammation. The inflammation may in turn impair healing, and you can get a cycle of inflammation and damage.

I don't think there's much evidence for the immune malfunction theory of Crohn’s, and the way I see it the immune system is only secondary. However, directly reducing inflammation may be necessary to stop the damage the inflammation itself is causing and may aid in the healing process.

The key, imo, is healing the damage and making sure it stays healed. To do that, you need to figure out what's damaging the intestine and how to get rid of it. AIEC or other pathogens certainly could be part of the picture here.
 
The 1985 article, that is worrying, as its almost 40 years old, and it mentions crohns has been researched extensively for a long time and yet they have not got anywhere.
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Dalziel and Lesniowski knew bacteria or fungi were behind the disease over a century ago. Rutgeerts and Harper in the 90s had the tools to prove it beyond a shadow of a doubt.

But in the 2000s we had a whole wasted decade where doctors and a handful of researchers hijacked the disease by focusing on an autoimmune theory, desperately trying to find some self-antigen they never found.

An autoimmune theory, as many pointed out at the time, which made no sense to begin with. Crohn's is not present in the whole organ, but involves patchy skip lesions, it is focused in areas with the highest bacterial load (ileal and colonic), and the granuloma are often indistinguable from those seen in other instestinal diseases involving bacterial translocation, like intestinal TB. Genetic predisposiion of Crohn's disease involves NOD2 and ATG16L1, responsible for bacterial recognition and xenophagy.

Now finally, in the last couple of years, research is back on track. The research from Clermont-Ferrand from the early 2000s (the "French research" Coombes talks about) is now being supported and confirmed by studies all over the world.
https://crohnsforum.com/threads/aiec-index.52198/

We have much more advanced technology today than in the 90s, complete genomic sequencing and research has mapped the virulence factors of bacteria like AIEC. How they behave, how they attach themselves to the epithelial wall, how they invade tissue and how they evade detection and elimination by the immune system. We are on a road that will hopefully lead to a targeted approach that is safe and effective, eliminating the troublemakers while minimally disturbing the bacterial ecosystem.
 
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Pangolin said:
I don't think there's much evidence for the immune malfunction theory of Crohn’s, and the way I see it the immune system is only secondary.
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It's an aspect in a subgroup of crohn's disease patience that simply leaves them more susceptible to the disease.

Genetic variations in genes like the ATG16L1 gene leave people more susceptibile to develop crohn's disease, specific proteins are involved in controlling how macrophages handle something called xenophagy (an innate defense mechanism against bacterial invasion).

But it of course can't explain the disease. Plenty of people who have these variants, do not have crohn's disease at all. In fact the large large majority of people with these variants do not have crohn's disease.

Most people with crohn's disease, especially thouse outside of the Western hemisphere, completely lack these variations, and yet they develop crohn's disease too.
 
In people with these genetic variants, the disease tends to be more severe than those without. Bacteria like AIEC can more easily evade the immune system in people with these genetic variants.

What some suggested is to screen people with crohn's disease for these variants. But I think it is good doctors have resisted this, it serves no point to the patient. The only thing it would do is scare the patient by telling them they have a variant, it won't affect their treatment and it is just needlessly throwing a psychological burden on their shoulders.
 
Unbelievable how many articles there were in that 2013 thread of yours kinny regarding Aiec.

I cannot read them all but I'll read some for sure.

What are your thoughts on mutations and crohns bacteria and future medicine?

The Aiec could mutate I guess, unless we get a medicine that can fully wipe it out ?

I guess the news with covid has made me think about mutations.

When will covid be over, that is beginning to be hard to predict.
 
sharkz said:
I think this is a very good theory as anecdotally my issues started after a bad case of food poisoning. Also makes sense how it can run in families, if families eat many of the same things together. However, this theory has been talked about since the 90's. I feel like if this was a solid theory, wouldn't there be appropriate treatments by now?
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Qu Biologics is in phase 2 iirc with a treatment that restores innate immune system function for crohn's patients, and I'm pretty sure there's also one that targets flagellin in the works, which is what bacteria need to infilitrate deep tissue and such, if I'm remembering right.

The pipeline that companies have mostly been incentivized towards is more suppressants, due to having to take those regularly and having broader applications, whether or not they understand the underlying causes correctly. When it's profit above all, what would be good for us doesn't often factor in, like that article about the treatment that cures a huge percentage of people with one type of hepatitis where it asked if curing people was a bad business model because then they're not repeat customers.
 
kiny said:
https://www.thelancet.com/journals/lancet/article/PII0140-6736(91)90663-A/fulltext

Rutgeerts his study showed that in people who had surgery, the disease returns just after a few months in other parts of the intestine that was previously unaffected, in the form of aphthous lesions.

Take note that these aphthous lesions are also the first endoscopic signs of crohn's disease when the disease is detected early.



However, any part of the intestine that is diverted from coming into contact with the fecal stream remains completely free of inflammation.


Rutgeerts and Harper then did follow up studies on this and started filtering the fecal stream with a ultrafiltrate, 22nm, which is small enough to filter out all the bacteria and fungi. Intestinal tissue of crohn's disease patients that comes into contact with that filtered effluent, show no inflammation at all. Neither in the ileum or colon.

The only explanation is that bacteria (or fungi) are causing the disease. Just like Dr. Coombes said, the initiation of the disease and maintainence requires a bacterial environment. Put it another way, in a world without bacteria, crohn's disease would not exist.

Giving chronic oral antibiotics might work very well initially, but eventually you create an environment where pathogenic bacteria become resistant and you now have a worse situation than you did before.

So you need a targeted approach to go after the pathogenic bacteria causing issues, like AIEC, and you leave the rest of the bacteria alone. Bacteriophages or FimH blockers for example.

https://pubmed.ncbi.nlm.nih.gov/9453485/
https://gut.bmj.com/content/gutjnl/26/3/279.full.pdf
Click to expand...

What's the reason, then, for Crohn's to get more aggressive and attack other parts of the body? Our doc said that it will attack the eyes and cause bone cancer and many other organs later. Not localized in the gut anymore.
 
Bacteria is getting in through the gut lesions and getting spread to other parts of the body, so my guess is that some of the extraintestinal manifestations are related to that.
 
Pangolin said:
Bacteria is getting in through the gut lesions and getting spread to other parts of the body, so my guess is that some of the extraintestinal manifestations are related to that.
Click to expand...

That sounds very scary. I don't even want to ask follow up questions anymore. This whole thing sucks.
 
Crohns is a progressive disease.

In terms of it always finds its way around the medication and does more damage, to date there is no medication or surgey that stops it progressing, biologics are slowing it down for the first time in history, but they do come with side effects.

There are side effects from crohns and side effects from medication..

Eyes is common, bone cancer not so common.

Bowl and skin cancer are more common.

Arthritis is common.

A weakened immune system, taking immune suppressive drugs, lack of ability to absorb correct nutrition are contributing factors, plus damage from inflamation is a contributing factor, plus some of the inflammatory pathways are are shared with crohns that are linked to other parts of the body.

Keeping inflammation at bay and getting the best nutrition possible is key.

Most crohns patients live a close to normal life, and have the same life expectancy as a normal human.

Research is progressing fast.. and if we all keep talking that will speed it up further.
 

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