Fecal Microbiota Transplantation for Recurrent C. Difficile in Inflammatory Bowel Disease.

[kiny]

Another study that shows FMT is completely ineffective for crohn's disease and leads to worsening disease in a significant number of patients.


FMT was used to resolve C difficile infection in CD and UC patients.

None saw improvements in crohn's or UC symptoms, and 7.6% had worsening crohn's or UC symptoms diagnosed as flares, requiring escalation of therapy.

https://academic.oup.com/ibdjournal...93/ibd/izz299/5673067?redirectedFrom=fulltext

Tariq R1, Disbrow MB2,3, Dibaise JK2, Orenstein R4, Saha S1, Solanky D1,5, Loftus EV1, Pardi DS1, Khanna S1.

2019 Dec 9

Mayo Clinic, Rochester, Minnesota, USA

BACKGROUND:
Clostridioides difficile infection (CDI) is associated with poor outcomes in inflammatory bowel disease (IBD) patients. Data are scarce on efficacy of fecal microbiota transplant (FMT) for recurrent CDI in IBD patients.

METHODS:
We reviewed health records of IBD patients (18 years of age or older) with recurrent CDI who underwent FMT. Outcomes of FMT for CDI were assessed on the basis of symptoms and stool test results.

RESULTS:
We included 145 patients (75 women [51.7%]; median age, 46 years). Median IBD duration was 8 (range, 0-47) years, 36.6% had Crohn disease, 61.4% had ulcerative colitis, and 2.1% had indeterminate colitis. Median number of prior CDI episodes was 3 (range, 3-20), and 61.4% had received vancomycin taper. Diarrhea resolved after FMT in 48 patients (33.1%) without further testing. Ninety-five patients (65.5%) underwent CDI testing owing to post-FMT recurrent diarrhea; 29 (20.0%) had positive results. After FMT, 2 patients received empiric treatment of recurrent CDI without symptom resolution, suggesting IBD was the cause of symptoms. The overall cure rate of CDI after FMT was 80.0%, without CDI recurrence at median follow-up of 9.3 (range, 0.1-51) months. Forty-three patients (29.7%) had planned IBD therapy escalation after CDI resolution; none de-escalated or discontinued IBD therapy. Overall, 7.6% had worsening IBD symptoms after FMT that were treated as new IBD flares. No clinical predictors of FMT failure were identified.

CONCLUSIONS:
Few patients had new IBD flare after FMT. Fecal microbiota transplantation effectively treats recurrent CDI in IBD patients but has no apparent beneficial effect on the IBD course.

 

[kiny]

These results are similar to the results of other studies.

In crohn's disease patients FMT shows no improvement in any patient after FMT, not in CRP, FC or histologic. And in around 10%-30% of patients you see significant worsening of disease, a significant increase in inflammation and flares requiring escalation of therapy.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6620877/pdf/10.1177_2050640619845986.pdf

''Department of Medicine, University of California San Francisco, San Francisco, CA, USA

Fecal microbiota transplant for Crohn disease: A study evaluating safety, efficacy, and microbiome profile

''We performed a prospective, open-label, single-center study. Ten CD patients underwent FMT and were evaluated for clinical response (defined as decrease in Harvey-Bradshaw Index score ≥3 at one month post-FMT) and microbiome profile (16S ribosomal RNA sequencing) at one month post-FMT.

The study was halted prematurely because of a presumed CD flare in two patients within a few days of undergoing FMT.

The first patient was a 37-year-old woman with colonic CD who had been diagnosed 10 years prior to enrollment in this trial. Her previous therapies included mesalamine and steroids. She was not on any therapy at the time of FMT. Within a few days of the procedure, she developed worsening abdominal pain and diarrhea. Her fecal calprotectin increased from 475 to >2000 µg/g. CRP increased from 2 to 15.5 mg/l and HBI increased from 3 to 16.

The second patient was a 32-year-old woman with colonic CD. She had been diagnosed 16 years prior to enrollment in the study. She had previously failed adalimumab and infliximab (responded initially with subsequent loss of response) and was on certolizumab at the time of FMT. She had required courses of steroids on several occasions but none in the last year prior to FMT. The day following FMT, this patient experienced increased abdominal pain and diarrhea severe enough to require inpatient admission for intravenous hydration and steroids. Her HBI increased from 11 to 13 post-FMT. CRP increased from 18.3 to 33.1 mg/l.

In this prospective, open-label study of FMT in CD, 30% of patients achieved the primary outcome of improvement of HBI ≥3 points one month post-FMT; however, there was no significant improvement in objective measures of inflammation such as fecal calprotectin and SES CD score.

Two patients in this cohort experienced adverse events requiring escalation of therapy within a few days of FMT that prompted early termination of the study.

Conclusions
Single-dose FMT in this cohort of CD patients showed modest effect and potential for harm''

 

[kiny]

The worst thing about these studies is that the gastros at Mayo Clinic employed ''empiric therapy'' and treated people with crohn's disease with FMT without having detected C difficile. On the suspicion of C Difficile, these patients were treated with FMT and several had worsening disease and no C difficile.

There is no justification for these mistakes.

Some of those gastros at Mayo clinic should be pulled by their ears and forced to read Rutgeerts his studies from the 90s that show the introduction of a fecal stream leads to flares in crohn's disease patients, before any of them are allowed to treat any more patients.

This is the second time in 6 months that gastros in US hospitals have actively harmed crohn's disease patients with FMT and have the audacity to make light of the situation.

 

[kiny]

The only beneficial information you can gather from these studies is how wrong the idea of an inflammatory response against the microbiota or even mycobiota is.

Dysbiosis is a secondary event in crohn's disease, the inflammation is not directed at the microbiota. FMT does nothing to help patients and the increase in bacterial load makes it worse.

The whole idea that the inflammation is directed at the microbiota is ridiculous beyond belief.

The inflammation in crohn's disease is directed at a specific intestinal pathogen, early signs of inflammation show inflamed peyer's patches and lymphoid follicles.

If the inflammation was directed at the microbiota you would have inflammation all over the intestine, you don't. The granuloma are very constrained macrophage responses deep within tissue. The inflammatory response is directed at PATHOGENS that have invaded TISSUE, it is not directed at the microbiota.

The inflammation does not start at the mucosal barrier, it starts in deeper layers of the lamina propria, the response is from deep tissue macrophages. The inflammation starts from within.

 

[D Bergy]

The only beneficial information you can gather from these studies is how wrong the idea of an inflammatory response against the microbiota or even mycobiota is.

Dysbiosis is a secondary event in crohn's disease, the inflammation is not directed at the microbiota. FMT does nothing to help patients and the increase in bacterial load makes it worse.

The whole idea that the inflammation is directed at the microbiota is ridiculous beyond belief.

The inflammation in crohn's disease is directed at a specific intestinal pathogen, early signs of inflammation show inflamed peyer's patches and lymphoid follicles.

If the inflammation was directed at the microbiota you would have inflammation all over the intestine, you don't. The granuloma are very constrained macrophage responses deep within tissue. The inflammatory response is directed at PATHOGENS that have invaded TISSUE, it is not directed at the microbiota.

The inflammation does not start at the mucosal barrier, it starts in deeper layers of the lamina propria, the response is from deep tissue macrophages. The inflammation starts from within.

My experience tells me the same. Remove the pathogens, remove the symptoms. The inflammation is deep in the tissue.

How to correct the immune system so it takes care of these pathogens like a normal person is now my focus. Haven’t cracked that nut yet.

Fecal transplants are much like blood transfusions. Neither should be done unless absolutely necessary. Introducing a whole host of unknown bacterium, fungus, viruses, etc into your body is a huge roll of the dice.

Dan

 

[paulk]

Fecal transplants are much like blood transfusions. Neither should be done unless absolutely necessary. Introducing a whole host of unknown bacterium, fungus, viruses, etc into your body is a huge roll of the dice.

I was under impression that it is very safe. If the donor is someone you know (like a child from the family) with no medical history wouldn't it be safe?

 

[Deleted member 431298]

Kiny, Thanks for sharing. That study is food for thought and it gives me a reason not to consider FMT (which I did - kinda').

My experience tells me the same. Remove the pathogens, remove the symptoms. The inflammation is deep in the tissue.

How to correct the immune system so it takes care of these pathogens like a normal person is now my focus. Haven’t cracked that nut yet.

Fecal transplants are much like blood transfusions. Neither should be done unless absolutely necessary. Introducing a whole host of unknown bacterium, fungus, viruses, etc into your body is a huge roll of the dice.

Dan

Dan, I believe that is where the new Site Specific Immunomodulators, SSI (vaccination-like treatments) are something to watch. QU Biologics SSI for example :
Qu Biologics Granted U.S. Patent for Use of E. coli to Treat Crohn’s Disease

I sincerely hope this line of treatment will finally be the long-lasting answer to all of our pains and troubles with this d*%# disease

 

[D Bergy]

I was under impression that it is very safe. If the donor is someone you know (like a child from the family) with no medical history wouldn't it be safe?

It certainly would be better to have a healthy close family member as a donor than not.

It really depends on what other options are available and what are the odds of success.

i am inherently cautious about anything introduced into the body, bypassing much of the immune system. You may cause yet another problem inadvertently.

A matter of potential risk vs rewards.

Dan

 

[kiny]

I was under impression that it is very safe. If the donor is someone you know (like a child from the family) with no medical history wouldn't it be safe?

Primum non nocere . Do not harm your patient.

FMT have lead to deaths in the past.

There is no indication that the inflammatory response in crohn's disease is directed at the microbiota itself, there is no reason why anyone should be treated with FMT for crohn's disease.

On the contrary, thanks to Rutgeerts and Harper we know that the fecal stream high in bacterial load leads to inflammation in crohn's disease patients. The introduction of a fecal stream in the form of FMT is completely counterintuitive.

The best evidence we have is that the inflammation in crohn's disease is a targeted (but incompetent) macrophage response directed towards pathogens and pathobionts that have entered tissue. Pathogens like invasive E Coli (AIEC) and certain fungi that we are able to recover from inflamed tissue with biopsies.

 

[kiny]

The only other disease that has the same clinical features of a deep tissue response with patches of granuloma where macrophages are causing deep transmural inflammation is intestinal TB.

If you suggested fecal transplants to treat intestinal TB, people would call you insane. You do not introduce fecal matter full of bacteria when a patient has active intestinal lesions like you see in crohn's and intesintal TB., you will cause more inflammation, more tissue damage and the risk of an uncontrolled infection or even sepsis.

Gastros experimenting with FMT on crohn's disease patients are in fact insane, incompetent, and liable.

 

[paulk]

There is no indication that the inflammatory response in crohn's disease is directed at the microbiota itself, there is no reason why anyone should be treated with FMT for crohn's disease.

I found a very small study confirming this (10 patients): https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6620877/

Conclusions
Single-dose FMT in this cohort of CD patients showed modest effect and potential for harm. Responders tended to have lower baseline alpha diversity, suggesting baseline perturbation of microbiota may be an indicator of potential responders to FMT in this patient population. Controlled trials are needed to further assess the efficacy and safety of FMT in CD and determine whether FMT is a viable option in this patient population.