Microbiome Breakthrough: New Crohn's Treatment Unveiled

[J100]

I came across this article. Research done by

https://www.miragenews.com/microbiome-breakthrough-new-crohns-treatment-1406399/​

@kiny , @my little penguin , @Scipio -your thoughts and comments

 

[my little penguin]

My two cents
You need to wait and see
Most mice models for various treatments don’t have large success rates in humans for Crohn’s disease
Fecal transplant doesn’t have high success rates at all for crohns
Een does have success in certain circumstances especially little kids since parents ensure compliance .
Een has its own risks though .
It would be nice if it were true but
Early stages
Needs more time /experiments especially on the fecal transplant side .
Een is a good treatment plan in the short term for kids and adults until you get a maintenance plan that works for you

 

[Scipio]

I agree with MLP. The mouse models for human IBD are pretty lousy. Something that works well in mice may or may not have much to say about human disease.

What they've got here is perhaps enough data to justify a small human safety trial. If it looks safe for humans then move on to an efficacy trial, but I'm not getting excited about any new therapy until I see the human clinical trial data.

 

[J100]

@my little penguin & @Scipio - I agree that models which work in mice may not work at all in humans. However, if this is successful then it will be great though it may take years for any such research to be fruitful.

 

[Michael Harrop]

The "mice" part is largely irrelevant. I would not call this a breakthrough or "new" treatment.

The liquid diet has existed for a long time. The microbiome and FMT are not exactly "new" but it's definitely surprising how many people are ignorant about it.

I don't find anything promising in this article. There have been plenty of FMT clinical trials. The problem is that people with "good enough" gut microbiomes to be highly effective stool donors are extremely rare. The people running the FMT clinical trials put little to no effort into finding such donors, so the trials they run are largely useless, and even harmful.

As a patient who's been following this area of research, and has been very frustrated by this, I've been trying to find such donors myself. The FDA stopped me and I've been staying in my car in DC since November, visiting the congressional offices most days, trying to get someone in the federal government to do something.

If you want to learn about this and help, read this.

 

[J100]

The "mice" part is largely irrelevant. I would not call this a breakthrough or "new" treatment.

The liquid diet has existed for a long time. The microbiome and FMT are not exactly "new" but it's definitely surprising how many people are ignorant about it.

I don't find anything promising in this article. There have been plenty of FMT clinical trials. The problem is that people with "good enough" gut microbiomes to be highly effective stool donors are extremely rare. The people running the FMT clinical trials put little to no effort into finding such donors, so the trials they run are largely useless, and even harmful.

As a patient who's been following this area of research, and has been very frustrated by this, I've been trying to find such donors myself. The FDA stopped me and I've been staying in my car in DC since November, visiting the congressional offices most days, trying to get someone in the federal government to do something.

If you want to learn about this and help, read this.

@Michael Harrop - A couple of years ago, I used to think that FMT could be a possible solution but after discussing it with a few people in in this forum, I am of the view that once the epithelial wall integrity is breached, FMT will not heal it or cause remission of a flare up. But that is just my opinion and I am not a doctor. I wish you all the best in your journey.

 

[kiny]

A healthy intestine is in a chronic state of low grade inflammation. The epithelial cells and the lamina propria are full of immune cells, abnormally high number of immune cells compared to other tissue in the body, indicating the intestine is a highly stressed organ.

Millions of naive immune cells originate in the thymus, travel through the bloodstream, end up in peyer's patches in the ileum and intestinal tissue. Many more are recruited when dendritic cells come into contact with antigen. That antigen comes from bacteria and the fecal stream.

These armies of immune cells are all triggered by bacteria or food antigen. The fecal stream is full of bacteria and food antigen. Using FMT to try to treat crohn's disease is like taking gasoline and throwing it on a fire.

That's why these FMT studies had crohn's disease studies where calpro jumped and they needed immediate escalation of anti-inflammatories. FMT is no longer pursued for crohn's disease, a good thing, because they would have eventually killed patients due to bacteremia. People with crohn's disease have deep transmural inflammation, granuloma where immune cells try to wall off fecal content. The last thing you want to do is expose these people to a FMT. It's dangerous, and it was highly predictable that this would not work and would cause adverse effects.

FMT does not work and harms patients. Doctors still doing this to patients need to be in jail, it is malpractice.

"21 and 13 patients were randomized to FMT and placebo groups, respectively. The trial terminated early due to futility. At week 8, 0% (0/15) of patients in the FMT group versus 8.3% (1/11) in the placebo group reached the primary end point of combined clinical and endoscopic remission as per protocol analysis."
https://journals.lww.com/ajg/fullte...ults_from_a_multicenter,_randomized.1438.aspx

"10 CD patients underwent FMT and were evaluated for clinical response and microbiomeprofile at one month post-FMT. There was no significant improvement in objective measures of inflammation such as fecal calprotectin and SES CD score. Single-dose FMT in this cohort of CD patients showed modest effect and potential for harm."
https://onlinelibrary.wiley.com/doi/10.1177/2050640619845986

 

[Michael Harrop]

@kiny's comment is misinformation. FMT is still pursued for Crohn's and UC: https://humanmicrobiome.info/ibd/#fmt-for-crohns-disease

The harm comes from low-quality donors. The link I shared in my previous comment has more info about donor quality.

 

[undone]

I know someone personally who underwent FMT almost 4 years ago now. The procedure completely failed and she needed to have emergency surgery to repair an absessed colon. She is still wearing a bag and hopes for a reversal when she is healed enough to handle it. No, thank you, FMT.

 

[Happy_]

A healthy intestine is in a chronic state of low grade inflammation. The epithelial cells and the lamina propria are full of immune cells, abnormally high number of immune cells compared to other tissue in the body, indicating the intestine is a highly stressed organ.

Millions of naive immune cells originate in the thymus, travel through the bloodstream, end up in peyer's patches in the ileum and intestinal tissue. Many more are recruited when dendritic cells come into contact with antigen. That antigen comes from bacteria and the fecal stream.

These armies of immune cells are all triggered by bacteria or food antigen. The fecal stream is full of bacteria and food antigen. Using FMT to try to treat crohn's disease is like taking gasoline and throwing it on a fire.

That's why these FMT studies had crohn's disease studies where calpro jumped and they needed immediate escalation of anti-inflammatories. FMT is no longer pursued for crohn's disease, a good thing, because they would have eventually killed patients due to bacteremia. People with crohn's disease have deep transmural inflammation, granuloma where immune cells try to wall off fecal content. The last thing you want to do is expose these people to a FMT. It's dangerous, and it was highly predictable that this would not work and would cause adverse effects.

FMT does not work and harms patients. Doctors still doing this to patients need to be in jail, it is malpractice.

"21 and 13 patients were randomized to FMT and placebo groups, respectively. The trial terminated early due to futility. At week 8, 0% (0/15) of patients in the FMT group versus 8.3% (1/11) in the placebo group reached the primary end point of combined clinical and endoscopic remission as per protocol analysis."
https://journals.lww.com/ajg/fullte...ults_from_a_multicenter,_randomized.1438.aspx

"10 CD patients underwent FMT and were evaluated for clinical response and microbiomeprofile at one month post-FMT. There was no significant improvement in objective measures of inflammation such as fecal calprotectin and SES CD score. Single-dose FMT in this cohort of CD patients showed modest effect and potential for harm."
https://onlinelibrary.wiley.com/doi/10.1177/2050640619845986

The microbiome can likely provide protection against certain diseases for some people (I find this to be the most likely explanation for the low rates of Crohn's disease in the first generation of immigrant populations in Western countries).

What can be harmful for certain disease states might be beneficial for others. Restoring the microbiome to a healthy state is very difficult, and FMT doesn’t guarantee success, even for individuals without IBD. However, in my opinion, the role of the microbiome and more specifically microbiome interventions, should definitely be studied further, as it plays a significant role in many chronic diseases, and anecdotally, its modulation can have a profound effect.

 

[J100]

I agree with @kiny and @undone. FMT can be harmful for Crohn's disease. A while ago, I had a chance to communicate with a gastroenterologist who had conducted trials in FMT and the results were not good. Therefore further trials were stopped. I also had a chance to talk to a hospital in Boston about it and they had also communicated that FMT in patients with Crohn's is not being done. If the evidence from clinical trials by a reputed university or institute points that it has not been helpful then we should accept that evidence. Apparently there is one doctor in Australia who swears by FMT but he is a lone case and I would still go by the evidence of the clinical trials.

 

[Michael Harrop]

I know someone personally who underwent FMT almost 4 years ago now. The procedure completely failed and she needed to have emergency surgery to repair an absessed colon. She is still wearing a bag and hopes for a reversal when she is healed enough to handle it. No, thank you, FMT.

I agree with @kiny and @undone. FMT can be harmful for Crohn's disease.

Did you guys just decide you didn't want to review the evidence I shared? Bizarre.

 

[kiny]

Of all the research that was done on crohn's disease, there is one name that stands out, Rutgeerts. The Rutgeerts Score is named after him. He is no longer around, but I had the privilege to talk to him at length.

In the 90s he showed that the fecal stream drives inflammation in crohn's disease. Without that fecal stream inflammation subsides. His findings have been repeated and confirmed multiple times. My opposition to FMT is rooted in this, epithelial contact with the fecal stream should be avoided, it leads to inflammation. When people with crohn's disease are put on IV feeds or EN, which limits fecal content, patients improve.

Interestingly, Rutgeerts showed that previously unaffected tissue develops crohn's disease in a few days after direct content with a fecal stream, which is exactly what you see in these FMT studies that had to be terminated.

"Within a few days of the procedure, she developed worsening abdominal pain and diarrhea. Her fecal calprotectin increased from 475 to >2000 µg/g."
https://onlinelibrary.wiley.com/doi/10.1177/2050640619845986

We also know that diverting the fecal stream in crohn's disease patients causes a large reduction in bacterial load in the ileum. So does taking EN or using IV feeds. So does filtering the fecal stream, a fecal stream filtered of antigen no longer causes inflammation.

"After fecal stream diversion, bacterial loads decreased significantly in the defunctioned ileum."
https://link.springer.com/article/10.1007/s10620-021-07060-9

When the fecal stream and bacteria are removed, the fire is put out. Not only in humans, in animal models too, one can not induce crohn's disease in a sterile environment. From this perspective, a perspective shared by decades of data that confirm Rutgeerts his studies, FMT makes no sense, and can actually worsen disease activity, which studies have now shown, patients needing an escalation of anti-inflammatory therapy after FMT, leading to early termination of studies.

 

[kiny]

It's not like these treatments trying to alter the microbiome haven't been given a fair shot. We have a decade worth of studies trying probiotics, prebiotics, now FMT. None work, not one reliable study can show probiotic works, not one reliable FMT study can show FMT works. The excuse that we need even more studies, harming even more patients, is baloney. The risks of causing bacteremia with FMT when performed on patients with deep inflammation are considerable, these are not harmless experiments.

What does work is limiting bacterial load, such as EN. It works in humans as well as animal models, the more sterile the environment, the less inflammation seems to occur. EN is highly effective, probiotics and FMT are not, there's no ambiguity.

 

[my little penguin]

Not necessarily true
I know probiotics work for my crohns kiddo. But he takes a specific prescription strength probiotic
Fmt has also worked for some
The bigger issue isn’t what works
But crohns needs a better classification or sub groups
Inflammatory arthritis has many sub groups and by making sub group classifications /types they now know different meds work for different sub groups
Crohns is a broad category that has a few sub groups imo