Crohn's Disease, Acne and Fecal Microbiota Transplant In Teenager - Remission Without Medication! 27 July 2013

I have hesitated in sharing my son's story with Crohn's Disease and the success we have had with FMT (fecal microbiota transplantation) until now because I didn't want to do so prematurely.

My son is 15 years old.  To protect his privacy, I will call him Jake, although that is not his real name :-).

Jake was diagnosed with Crohn's Disease a few days before his 13th birthday.  It was widespread ulceration, inflammation and infection throughout his duodenum, terminal ileum, ascending colon, descending colon and rectum.  It was a "gut-wrenching" time for me as a mother to an only child, especially after being told how very serious this disease is, how extensively he had it, that he would have it for the rest of his life, and probably do poorly in the long-term because he was so young at diagnosis. 

I was worried sick with the long term consequences of my son taking immune-suppressive drugs (in his case, Imuran) - on the other hand I was terrified of the consequences of Crohn's Disease and felt we were between a "rock and a hard place".  I cannot begin to put into words just how heartbroken and helpless I felt, but I am sure that any parent who reads this will understand.

Professor Tom Borody was recommended to us by a family friend as being an outstanding gastroenterologist.  Unfortunately he was unable to treat Jake until he turned 14 as he was a paediatric patient, however tests he was able to order showed that Jake also had a strain of c-diff (clostridium difficile) - it was not the worst strain, but Prof. Borody felt that we needed to get rid of that first.  It was what he called a "super infective".

Within days of his 14th birthday, Jake had a gastroscopy and colonoscopy.  The Imuran had certainly helped to take care of the crohn's in his colon - however his terminal ileum was still swollen, inflamed and pussey.  His duodenum, still had some crohn's-like ulcerations.  Prof. Borody recommended FMT to kill off the c-diff and we proceeded to have suitable family members tested as potential donors.  Jake began a three week course of oral vancomycin to weaken the c-diff and then in April 2012 had his first FMT via colonoscopy- his terminal ileum was still very inflamed and swollen.  I continued to administer FMT treatments to Jake at home and his 14 year old cousin was the donor.  We also continued his Imuran.

A remarkable and unexpected bonus to having the FMT was that acne that had plagued Jake for the past year and a half had completely disappeared 7 days after treatment began.  It has never returned!!

In November of 2012 Jake had a colonoscopy and endoscopy.  To Prof. Borody's surprise, Jake's colonoscopy was perfect - the terminal ileum looked normal, as if there had never been a problem!  The only trace was one single tiny erosion in his duodenum.  There was no trace of c-diff either!

As advised, we reduced his Imuran and gradually over the next few months.  Jake was completely off his medication by March 2013, so as at the time of writing, it's been almost five months.  Jake is growing tall, his appetite is huge (perfectly normal for a healthy teenage boy) and he is putting on weight appropriately for his age.  I still do top-up FMT treatments every 3 to 4 weeks - it's difficult to know exactly when the right time to stop is - in total he has had well over 115 treatments.  Prof. Borody says that Jake needs to develop his own microbiota.  

I do not know if FMT offers a cure for crohn's disease - but I do know that there is no way my son would have been able to sustain any remission without medication prior to this as we had tried a couple of times to reduce his Imuran but both times his symptoms came back within two weeks.  What I do know is that FMT has tremendous potential for Crohn's and other diseases and definitely needs further studies.  I also have to stress the importance of stringent donor testing.

I will keep you all posted in the months ahead of Jake's progress, but thus far, as a mother, I cannot be more delighted with how well this has gone.  I am also so incredibly thankful for Prof. Tom Borody for being one of those scientists who dares to think "outside the box".  It is because of doctors like him that medicine advances instead of remaining stagnant.  It is because of him that Jake's future is looking good instead of bleak and that I can cry tears of happiness and gratitude instead of despair.


(Please click here to read part 2 of "Jake's" Story - November 2013 (One year later) - Colonoscopy/Gastroscopy showing no sign of Crohn's Disease whatsoever - NOT even in his duodenum!)

Multiple Sclerosis and Fecal Microbiota Transplant

With World MS Day being 29th May, it seems appropriate to post a link to a previous entry about Multiple Sclerosis and Fecal Transplant.

The link is to three case studies from Centre of Digestive Diseases, Sydney Australia (Professor Borody).   Three of his patients who had multiple sclerosis were treated for constipation (one of the many complications of this terrible disease) and to their's and Professor Borody's surprise, their MS symptoms unexpectedly also disappeared, so much so that as at the time of writing the study all patients remained in remission, one of them for 15 years!  Professor Borody speculates that a gut pathogen may be responsible for causing the neurological disease and encourages a new direction in medical research of MS.

http://www.fecalmicrobiotatransplant.com/2012/08/could-multiple-sclerosis-be-caused-by.html

FMT Success Story For Pediatric UC Patient!

This story comes from a mother who posted as a visitor on http://thepowerofpoo.blogspot.com.au/ - it's a very powerful story showing the tremendous results that FMT can give to a IBD sufferer (a child). It's definitely worth reading!

Kathy's Success Story

"Hi, I’m Kathy, mom to a nine-year-old girl diagnosed with Ulcerative Colitis in January 2012 and successfully treated with FMT. I don't want to know where we would be now if we hadn't tried it, or if it hadn’t worked. We went through seven months of hell trying to get her better before we started FMT. Here’s our story:

E's symptoms appeared out-of-the blue. On Christmas Eve 2011, she called me into the bathroom to look at her wipe, which had some blood on it. Over the next few days, we noticed that her stool, though completely formed, had some visible blood coating the outside of it. I didn't make too much of it, which is surprising since I tend to be a bit of an alarmist when anything seems out of the ordinary. I thought that she had picked up salmonella after playing with a lizard in the yard and that the blood would resolve, and we would move on with our lives. I was totally wrong.

Within three-and-a-half weeks of the onset of bleeding, E had a colonoscopy, which showed inflammation in her colon. E was diagnosed with IBD, and more specifically, Ulcerative Colitis (and even more specifically, proctosigmoiditis). The good news, or so I thought, was that only her rectum and sigmoid colon were involved. The doctor thought so, too and said E would have to be on Asacol for at least a year, but that it should work to control the symptoms. At that point, I didn’t know anything about IBD, including that it was considered an autoimmune disease whose only “cure” was a colectomy. Yikes.

Well, Asacol didn’t work. And neither did sulfasalazine, flagyl, prednisone, mesalamine enemas, hydrocortisone enemas, cortifoam and canasa suppositories. What?!?! How could that be? Well, apparently, there are cases of UC that are refractory, or not responsive to medication. But, at that point, we hadn’t hit the big guns yet — 6-MP or Remicade, so we weren’t there yet.

In the meantime, we met with a surgeon. He told us that E might need a colectomy. It was the worst appointment of our lives. He wasn’t nice or compassionate. It seemed like he just wanted to cut open my kid and take her colon—no big deal. E said there was no way she was having her colon out. She said she didn’t need the surgery. I wanted to believe her, but I wasn’t sure we were going to be able to beat this thing. With more and more meds, she was just getting worse and worse as time went on. Her hemoglobin and hematocrit started dropping. She was getting more and more tired and lying around the house instead of climbing trees and running around. She was looking terrible. She was waking in the night to use the bathroom. I felt like I was losing my daughter.

I had been frantically doing research all along, searching for alternative things to try. We tried various supplements—bovine colostrum, homeopathic phosphorus, turmeric, fish oil, cod liver oil, vitamin D, VSL, Chinese herbs— acupuncture, and two diets—SCD/paleo/GAPS (though admittedly we only followed it about 90%) and Jini Patel’s “stop intestinal bleeding diet”. I first heard of FMT from a good friend of mine before E was even diagnosed with UC, when the bleeding had first started. I remember being so afraid to try it. I didn’t want to put anything in her rectum or colon for fear of making things worse. I couldn’t bear the thought of hurting my daughter more than she was already hurting. And I always thought poop was kind of dirty — I mean, we wash our hands after we use the bathroom, after all. Our doctors didn't know anything about it and pretty much changed the subject when I brought it up at appointments. So, I went ahead and purchased a home FMT protocol online.

Then, I researched more and looked for support from other parents whose children have IBD. FMT looked to me like the most likely treatment to help E. I learned that people were doing FMT for UC and were being helped by it, but many were doing it without support from their doctors. I knew Borody’s research, I read about the Bright Clinic in Oregon, and I was in touch with someone who had successfully done FMT for his seven-year-old son. I read countless IBD forums. I learned that healthy stool is full of healthy bacteria and that if put into the colon of a person with UC, the bacteria would recolonize in the sick person’s colon and help it heal by restoring the balance of bacteria that was likely out of balance. But, I was wary about doing FMT without the support of our doctors. We were dealing with a child, and I was terrified that if I tried something like putting someone else’s poop into my daughter’s colon and she got sicker, I would get in some serious trouble.

In April 2012, we had plans to travel 1000 miles for a second opinion at one of the top pediatric IBD centers in the country. The day before we left, E’s bleeding was getting worse and worse. Her tummy was aching, her knees were hurting, and she literally had to run to the bathroom every couple of hours. The bowl was red every time she went. I was a mess. We decided to give 6-MP a try, since our doctor at home assured us that our second opinion would give us the same advice. I felt that if she didn’t get better soon, we were going to be in trouble. So far, we had been able to keep E out of the hospital, but just barely. Every few days we were talking with the doctor, deciding whether to hospitalize her or try to keep her home. It was torture.

At our second opinion appointment, the doctor confirmed what our doctor had said, but he also had statistics. There was a 50% chance that 6-MP would work for E, and a 60% chance that Remicade would (and even if Remicade worked, there was no guarantee it’d work forever). And that was the end of the road. If neither of those medications worked, her colon would have to be removed.

Shortly after, we decided to try FMT. I got the ball rolling on getting E into the first U.S. clinical trial for FMT in children. It turned out she was a good candidate. Unfortunately, the timing didn’t work out. We could tell by her blood work that she wouldn't be likely to stay on 6-MP even though her symptoms had improved quite a bit. In the end, we decided to take advantage of her improved status on 6-MP and try FMT before she had to discontinue it.

Fortunately, with some pushing and pleading we finally persuaded our doctors to support us in FMT. They gave us a protocol (it was the protocol for C. Diff written by Silverman) and a list of blood and stool tests for the donor to have done. We wanted a donor with good digestive and overall health. My husband has IBS, so he was out. I have always had a good gut as far as I know, but I still had all the tests to make sure there were no hidden problems. Two months prior to my first donation I was on antibiotics, but it doesn’t seem to have affected the quality of my donation.

We started FMT in August last year. We began with a 10 day triple antibiotic therapy followed by 5 consecutive days of FMT, followed by twice-weekly FMT. Within 24 hours of the first enema what little bleeding there was had stopped. Within 3 months, E’s bowel movements reduced to 2-3 times daily. Throughout we have continued with sulfasalazine and FMT twice a week. E continues to do just great and her labs look awesome. The biggest improvement we saw in the labs was six months post-FMT when her calprotecin had dropped from a high of 1014 when she was flaring to her current level of 60.1.

It’s now seven months since we started FMT and E is 90% better. We are still doing FMT twice weekly and E still has some minimal food restrictions, which is why I don't say she is 100% better. She says she feels better than she ever has. She looks beautifully healthy. We have kept up the FMT because we believe the intestines take a long time to heal, and because we don't think it can hurt. While we have faith in the treatment, we don’t want to stop it yet, either.

My advice for people considering FMT is to talk to others who have done it and to try to find a doctor who will support you, if that’s important to you. After doing all the research I did, I felt very confident in the potential of FMT and strongly believed that we had nothing to lose by trying it. When the top researchers in the country told us that the best they can do is give your child a dangerous drug that has a 60% chance of working or they can cut out her colon, which has countless potential complications, I felt it was time for us to look at other options, and FMT seemed to be the best one by a longshot.

My daughter was only sick for seven months, but it was the worst seven months of my life. I cried every day for six of those months. People kept telling me that she would get better, but I stopped believing them. But then, we fixed her. WE brought her back to health! And now our doctors are trying the treatment on other patients, and a family member who is in pediatric gastroenterology convinced her boss to try FMT on patients (they have done two so far!) There is no greater feeling than, even in some little way, to help someone regain the health of his or her child. What a roller coaster it has been — we went from feeling completely lost and scared to feeling like we can point people in the right direction and optimistic that our daughter is going to remain well.

The best advice I can give someone trying to make a decision about FMT is that you will know if and when it is time for you to do FMT. Nobody can make the choice for you. We are all on our own journeys and have to find our own paths. There are many ways to wellness, and FMT may be yours. There are people out there doing it and doctors are starting to do it. But, these things are slow to get going in the medical field, and sometimes time is not on your side. It certainly wasn’t for us — we just did our research and did what we felt we needed to do for our child, and FMT was it. While it can be overwhelming at first, the prep is easy and the administration is even easier. I would do FMT every day for the rest of my life if that is what we needed to do."

If you are the parent of a child with UC and need support in making the FMT decision, Kathy is willing to help. Please visit http://thepowerofpoo.blogspot.com.au/  and the blogger, Tracy can send your details to Kathy so that she can contact you.

Fecal Microbiota Transplantation - New England Journal of Medicine Reports 94% Cure Rate for C-difficile

The results of a randomized controlled study has been published in the New England Journal of Medicine this week which showed a 94% cure rate for clostridium difficile as opposed to 31% of patients taking the antibiotic vancomycin. The study was stopped prematurely becase the results were so outstanding for those who were given fecal transplant that it was considered to be unethical not to offer the treatment to all patients participating in the study. Read more below courtesy of the New England Journal.nbsp;  Here is a link to the study:

Duodenal Infusion of Donor Feces for Recurrent Clostridium difficile — NEJM

and a link to the editorial written by Ciarán P. Kelly, M.D.

Fecal Microbiota Transplantation — An Old Therapy Comes of Age — NEJM

"Fecal Microbiota Transplantation — An Old Therapy Comes of Age

Ciarán P. Kelly, M.D.

January 16, 2013DOI: 10.1056/NEJMe1214816

In 1958, doctors in Denver administered feces by enema to their patients with fulminant, life-threatening pseudomembranous enterocolitis.1 The goal of this infusion of donor feces (also termed fecal microbiota transplantation [FMT]) was to “re-establish the balance of nature” within the intestinal flora to correct the disruption caused by antibiotic treatment. They reported “immediate and dramatic” responses and concluded that “this simple yet rational therapeutic method should be given more extensive clinical evaluation.” During the ensuing 50 years, the association between Clostridium difficile infection and pseudomembranous enterocolitis was established, and effective antimicrobial treatments were identified. Despite these advances, C. difficile became the most commonly identified cause of nosocomial infectious diarrhea in the United States. During the past decade, there has been an alarming increase in the incidence and severity of this disorder, with associated increases in mortality and economic cost.2

Although most patients with C. difficile infection have a response to antimicrobial therapy, approximately 25% have a recurrence after the initial treatment course.2 Patients with a first recurrence of C. difficile infection are more likely to have a second recurrence (risk, 35 to 45%), and for patients with multiple recurrences, the subsequent recurrence rates surpass 50%.2-4

Only patients with the most recalcitrant cases of C. difficile infection are likely to undergo FMT, usually out of desperation after multiple treatment approaches have failed.5,6 Yet, systematic review reveals that the reported efficacy of FMT in treating recurrent C. difficile infection is greater than 90%.6 So why has FMT not become routine therapy for C. difficile infection during the past 50 years? There are three main reasons: it is aesthetically unappealing, it is logistically challenging (in terms of harvesting and processing suitable donor material), and there is a lack of efficacy data from randomized, controlled trials.
 

The last impediment is addressed in a report on a randomized, controlled trial by van Nood et al.,7 now in the Journal. In this study, investigators compared the duodenal infusion of donor feces after vancomycin therapy and bowel lavage with vancomycin therapy either alone or with bowel lavage. The study was unblinded and imperfect. Nonetheless, the outcome favors FMT (81% response) above vancomycin therapy either alone (31%, P<0.001) or with bowel lavage (23%, P<0.001) in patients with relapsed C. difficile infection in whom standard therapy with vancomycin has failed. The trial was closed to new enrollment by its data and safety monitoring board after only 43 of a planned 120 patients had undergone randomization because almost all patients in the two control groups had a recurrence. The finding that FMT was effective in 81% of patients with recurrent C. difficile infection is consistent with a systematic review of uncontrolled case series in which FMT through the stomach or small intestine showed an overall response rate of 80%; the anecdotally reported overall response rate for FMT through colonoscopy or enema is 92%.6 Thus, this study and the previous case series yield consistent, strongly positive results.

The study by van Nood et al. is an important confirmation of the efficacy of FMT for recurrent C. difficile infection. Their findings will provide added stimulus to the ongoing efforts to address the other main impediments to the routine and widespread use of FMT. Natural antipathy toward fecal therapy can be reduced by banking suitable material from anonymous, screened donors.8 Such a system would both distance the recipient from the stool donation and provide physicians with readily accessible, quality-controlled treatment materials. Ultimately, the use of feces may be eliminated in favor of defined mixtures of cultured bacteria that confer colonization resistance against C. difficile, an approach that was pioneered by Tvede and Rask-Madsen in 1989 and is now being examined afresh.9 The later approach can also assuage concern regarding the inadvertent transmission of disease-causing pathogens through FMT. These advances can make intestinal microbiota therapy acceptable and accessible to most patients and their physicians. It will also facilitate the “more extensive clinical evaluation” of FMT for severe, refractory C. difficile infection, as first advocated in 1958.1

 

 

The significance of the study by van Nood et al. goes far beyond the treatment of recurrent or severe C. difficile infection. The burgeoning field of microbiome research, initially made possible by technologies to identify bacterial 16S ribosomal RNA in complex biologic samples, has alerted us to the abundant, diverse, and influential nature of the gut microbiota.10 Microbiome research has been expanded and complemented by methods to characterize the protein composition (proteomics) and metabolic processes (metabolomics) of the intestinal contents and those from other body sites. The results of this study represent a clear precedent in which planned therapeutic manipulation of the human intestinal microbiota can lead to demonstrable, clinically important benefits, thereby bringing FMT to the mainstream of modern, evidence-based medical practice.1,5-9 The study by van Nood et al. will encourage and facilitate the design of similar trials of intestinal microbiota therapy for other indications, such as inflammatory bowel disease, irritable bowel syndrome, prevention of colorectal carcinoma, and metabolic disorders, to name just a few.10 As such, it heralds the delayed adolescence of a broad and exciting new branch of human therapeutics.

References

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