Analysis of Crohnology’s Fecal Microbiota Transplantation Users: An Open Source Peer-to-Peer Observational Treatment Study

If you don’t appreciate what the next sentence says it doesn’t really matter. Patient social networks will do more for observational studies than what the Cochrane Collaboration has done for randomized control trials. What matters is that you tell your story. Your experience with treatments and medications is evidence. Patient’s stories should never be dismissed as anecdotes (it’s not only dehumanizing it’s a misuse of the word anecdote). We, the patients, need not have to purchase a credential and malpractice insurance to read case stories written by each other. Let’s, for a moment, never mind Abbott and AbbVie, Bad Pharma, the institutionalized biases produced by monetary incentives, case law, cancer, class actions, the FDA, Pharmageddon, insurance, The Truth About Drug Companies, marketing budgets, Obamacare, side effects, Overtreated, iatrogenesis, Vioxx, and Viagra. Let’s investigate a democratized disruption in action, a patient social network. Let’s use it to add outcome results to the literature of a procedure that shows promise for many chronic conditions and costs less than my monthly cell phone bill. But before you think this article is all roses…

This article is about the benefits of ingesting poop. Yep, poop. There’s a pile of names for what I’m talking about: Bowel Flora Alteration Therapy, Stool Transplantation, Human Probiotic Infusion, The Ultimate Probiotic Retention Enema, Gut Flora Upgrade, Fecal Bacteriotherapy, Poop Transfer, and Fecal Microbiota Transplantation (FMT). I’ll use FMT and I hope you’re not disappointed. I prefer Flora Upgrade (FU) but perhaps it sounds too casual or too much like adding a few tulips to the garden. In medical literature FMT is defined as “the introduction of a fecal suspension derived from a healthy donor into the gastrointestinal tract of a diseased individual”[1]. Usually FMT is administered by enema or colonoscope although there’s also nasojujunal. But that just seems wrong. Donor, poop, salt water, blender, enema. That’s the procedure we’ll investigate. And in case there’s any confusion here’s an instructional YouTube video featuring a chocolate covered banana: DIY Fecal Transplants to cure yourself of digestive disease.

Enter our patient social network: Crohnology. I’m a member. I have Crohn’s disease. It’s an Inflammatory Bowel Disease. Ulcerative Colitis (UC) is another IBD. I was so excited about joining I drove 1,178 miles to attend their launch party back in July of 2012. To respect the largely ignored tradition in medical research of disclosing conflicts of interest here are my disclosures: I received a free Crohnology tee shirt, a 10 minute chair massage, and various selections from a vegetable plate. I’d like to reveal I’m not a ghostwriter from Crohnology’s marketing department. Additionally I’m not a professor being paid to put a brand name academic stamp-of-approval on a paper I didn’t write which analyzed data I didn’t collect. In fact Crohnology is not paying me, even in fresh brown slurries, for writing this. I’ll reveal my reasons. Crohn’s disease is deadly painful. It’s unbearably socially isolating. It’s chronically misdiagnosed, mistreated, and misunderstood. It can kill. The drugs prescribed to treat it have unbearable side effects and can kill on their own. I don’t want to be in pain or take unnecessary medication. Someday I may have to try FMT. Another reason for my participation is to draw attention to what patients can achieve with the creative organization of a focused social network. Wellness and knowledge about treatments could all grow from the bottom up instead of marketed, profited, and legislated from the top down. The bazaar please, not the cathedral. Pave the way for informed choice and flush the paternalistically prescribed pills. There’s implicit trust. For determining the long term effects of treatments, who better to follow up with, than with each other? If we let them patient social networks can become our healthcare culture. One of the founders of Crohnology, Sean Ahrens, also has Crohn’s. Our incentives are aligned by default. This is from Crohnology’s About page: “We envision a world in which every patient can instantly tap into the knowledge and experiences of every other, so that every patient can learn how well treatments have worked for others, whether they are alternative, experimental, or prescription.” I envision that world too and this is my contribution.

Crohnology is new technology and its users are early adopters. But FMT, like a lot of new medical treatments, dates back to ancient China. During the Dong-jin dynasty of about the 4th century Ge Hong recorded the use of a human fecal suspension for the treatment of diarrhea. This is recorded in Hong’s book, Zhou Hou Bei Ji Fang, which gets translated a number of different ways: Handy Therapy for Emergencies, Emergency Standby Remedies, and even Emergency Formula Kept in One’s Sleeve. Fast forward to the 16th century during the Ming dynasty when Li Shizhen composed the classic medical compendium, Ben Cao Gung Mu, which “describes a series of prescriptions using fermented fecal solution, fresh fecal suspension, dry feces, or infant feces for effective treatment of abdominal diseases with severe diarrhea, fever, pain, vomiting, and constipation” [2]. There are also veterinary references to FMT. The earliest is credited to Fabricius d’Aquapendente in the 17th century [3]. More recently horses with colitis have been given FMT. Similarly, sick cows get transfaunation, which is like a fecal transplantation but in place of poop substitute rumen material from a healthy cow [4]. But all that is probably not doing justice to the benefits of ingesting excrement. I imagine dogs have been giving themselves self administered oral FMT since the dawn of the dog. And dogs aren’t the only ones. I like elephants. I was curious to know if they partake in poop eating. It turns out that not only do calves eat an abundance of adult elephant dung it’s nicely explained in a short YouTube video: Baby elephants eating dung – BBC wildlife. Here’s some commentary: “Dung has a surprising use for young elephants. It contains the vital bacteria that break down plant cellulose. This kick starts an infants digestive system.” The list of animals who participate in coprophagia is too long to list. Perhaps they’re on to something.

To understand the mechanism of action involved in FMT it’s useful to know that the human microbiome is the sum of all the microorganisms you’re hosting. It’s your personal ecosystem of bacteria and fungus and such. Your gut microbiota is the distribution of microorganisms living in your gut. It has an intimate connection with your immune system. When the distribution strays from healthy inflammatory diseases can happen [5, 6, 7]. The overriding point of FMT is to reestablish a stable microbial ensemble in the gut [5]. It’s been observed that IBD patients have a significantly reduced level gut biodiversity [8]. Unfortunately the role of gut microbiota is complicated and mostly unknown. There’s 10 times more bacterial cells in our body than human cells. To illustrate the point: “Recent metagenomic sequencing analysis established a human gut microbial gene catalogue, identifying 3.3 million nonredundant microbial genes, approximately 150 times larger than the entire human gene complement. The GI microbiota and their genetic products exist in a complex, but balanced homeostasis and have important roles in nutrition, energy metabolism, host defense, and immune system development” [1]. And how does my microbiome relate to my epigenetics? Let’s not even go there. As I was writing this I came across the September 6, 2013 New York Times article titled In Gut Research’s Latest Advance, Bacteria From Thin Humans Can Slim Mice Down. They gave mice FMT using human donors! Attempts at using FMT for human weight loss are not far away. FMT will probably turn out to be useful for all sorts of inflammatory and immune system ailments. So perhaps that pooch in the park who’s so fixated on the other dogs’ output is sniffing out a healthy distribution of microorganism to add to its doggy microbiome. Perhaps the behavior is ultimately for immune system maintenance and general health. We don’t know.

Although the Inflammatory Bowel Diseases are still poorly diagnosed by medical professionals [9] both Crohn’s and UC became distinguishable in the first half of the 20th century [10]. The first reference I could hunt down of FMT used in an official Crohn’s diagnosis comes from Australia in 1989. Here’s the case report: “A 31-year-old man was admitted to hospital with small-bowel obstruction, which subsequently was shown by a small-bowel barium-enema examination to be caused by Crohn’s disease of the terminal ileum. This was confirmed by examination of a terminal-ileal biopsy specimen. In spite of prednisone and sulphasalazine therapy, hypoproteinaemia with ankle oedema was prominent, presumably as a result of protein-losing enteropathy. Three days after alteration of the bowel flora, his ankle oedema had disappeared and the serum protein levels had returned to normal values. He remains free of symptoms and is not receiving any therapy four months later” [11]. This is all that’s written about the patient and his procedure. Sounds promising but I’m confused and desperate for details. Did the patient get a small bowel resection, which didn’t work, and then FMT some time later? If not, and FMT was administered soon after removing a portion of the diseased intestine, then we can’t know why the symptoms cleared up. One thing at a time please. Measure the result. Then do something else. Be clear and detailed. Explain the timeline. Don’t write a crappy case report. Coincidentally this patient sounds like me back in 2007 when I had surgery to remove my terminal ilium. Four months later I wasn’t having my usual Crohn’s symptoms and I’ve not experienced a post surgery obstruction [12]. I’d like to hear the patient’s version of the story. How’s he doing now? He’d be a 55 year old Australian. Can we track him down get him to sign up for Crohnology?

So here’s one way Crohnology trumps the tradition: The patient builds a living case report. Here’s an example of one of my Crohnology friend’s health history. Her name is Jessica B. and she’s a 25 year old from Nashville, Tennessee. She’s had UC for 11 years and had a total colectomy. She’s currently taking Imuran, Rowasa, and Apriso.

A Screenshot of Crohnology's Health Timeline - A Living Case Report

A Screenshot of Crohnology’s Health Timeline – A Living Case Report

The pins in the timeline indicate notes. Scroll over a pin and you can read her notes. For example on Monday May 20th 2013 she writes: “Fecal transplant complete! Doc says should be 48 hours until I see real changes, but I’ve already stopped bleeding and actually felt hungry for dinner…” Her post FMT progress is clearly laid out on the timeline. She goes from Meh to Fantastic! in a month after FMT. As long as Crohnology and Jessica stay together I’ll be able to follow her progress. Will Crohnology someday be integrated into my electronic medical record with the click of a “Share my Crohnology profile with my medical professional” button? This way a physician can be visually reminded not only of my complete health history including my age, weight, medications and procedures, but of other important things: Like my name [12, 13].

A feature of Crohnology allows its members to view everyone who’s tried a particular treatment whether it’s Pig Whipworm (9 people), Medical Cannabis (179 people), or Probiotics (1119 people). There’s over 100 different treatment categories and thousands of Crohnology members. Treatment users can review their current and past treatments with a star rating similar to how a critic summarizes a film. Four people have rated FMT. Three rated it with 5 stars and one gave it 4 stars. There’s also a place for users to write a review. Here’s what four FMT treatment users say:

“First Transplant is March 14th – have had 2 weeks of success. System seems to stay fairly balanced – dr says I just need to heal now.”

“Totally normal after 3 infusions, but got a virus in the middle of treatments. Still helped a lot. Did a second round Feb 2013. Now totally normal.”

“I did a transplant in 2012 which worked like a charm after 3 transplants. I did not follow up and was symptom free for 14 month. After this I had a bad flare and tried the FT again. First time – no effect, 2nd time it made my flare worse. So I had mixed results. I would try it again during my next flare!”

“I got worse! But I would try again in the future. I was doing pretty horribly when I tried it. I think it was too much to handle.”

All this is a strong upgrade from 1989 but let’s push treatment investigation past Crohnology’s built in features. Let’s use the platform as a vehicle for discovery and make an original contribution to the FMT literature as it applies to IBD. Two weeks ago, with the blessing of Crohnology, I sent everyone who had FMT a survey with questions patterned after the analysis in a paper called Systematic review: faecal microbiota transplantation in the management of inflammatory bowel disease [14]. Since I have Crohn’s, am a member of Crohnology, and a potential FMT recipient someday, perhaps we can call this peer-to-peer observational treatment research.

The first interaction I had with my fellow Crohnology members as a peer researcher was an introductory message asking if they’d like to participate in a survey about their FMT experience. I also sent a friend request. There are a total of 11 past and current users of FMT listed in the FMT treatment section of Crohnology. But upon taking a closer look one person had created two profiles and isn’t an active user. Inactivity goes for another user. That leaves 8 users of which one didn’t actually have FMT. She had a probiotic retention enema which Crohnology hasn’t yet listed as a treatment category. In her defense FMT is the closest treatment to what she tried but we can’t count her in the survey. This leaves 7 FMT users. All of them acknowledged my friend request and expressed willingness to participate.

Since my survey seemed a bit long, and Crohnology didn’t want participants overwhelmed with an email, a developer quickly built a survey platform. By quickly I mean 2 days. With Crohnology’s new survey feature participants see a well designed interface with a clearly designated question. The responses came fast. The first FMT survey participant happened to be online when I sent a link to the survey. (She had it completed before I was done daydreaming about who my FMT donor would be and where could I get a cheap blender.) She spent 7 minutes and 32 seconds filling out the survey. Over the next 31 hours I received another 5 responses. Six out of an expected 7 within two days is phenomenal response. The average time to fill out the survey was 13 minutes. One week after collecting the results I still haven’t heard from one of the FMT users.

Like most people I use my real name when using Crohnology. Others tend to use a first name and last initial. Since we’re releasing the raw data outside the Crohnology community I’ll refer to the survey respondents by their initials. This just became open source peer-to-peer observational treatment research. By the way you are entitled to the raw data. It’s a public health issue. It’s a human right. Raw data is clean water. Demand it.

Of the 6 respondents 3 had a diagnosis of UC, 2 Crohn’s and 1 Irritable Bowel Syndrome (IBS). IBS is different from IBD but has similarities. I’ve heard IBS is a diagnosis of exclusion but this is contradicted by the IBS Wikipedia page. To me IBS seems like a catch all for a physician to acknowledge there’s clearly something wrong but doesn’t know exactly what. The IBS diagnosis itself seems like evidence that modern medicine really has no idea of the complexity of the gut. It’s a different story but I was misdiagnosed by a family practitioner as having IBS [15].

Two of our 6 survey respondents were treated with FMT because of Clostridium difficile infection (CDI). This complicates our plight for knowledge about FMT being useful for IBD. The symptoms of CDI and IBD overlap (bloating, diarrhea, abdominal pain, fever, etc.) The good news is that since at least the late 1950′s FMT is well known to cure even the most recalcitrant cases of CDI [1-4, 16, 18]. A serious issue to acknowledge with this research is this: For the two participants who received FMT for CDI, how can they know the difference between the effect of FMT on their CDI versus IBD symptoms? It’s an open question.

All 6 respondents have had FMT in the past year. Four were self administered and 2 were overseen by a physician. All 6 were also responsible for finding the donor material: 3 used a spouse, 2 used Mom poop, and 1 used an unrelated donor. All used fresh as opposed to frozen. In all cases the fecal slurry was prepared using a blender, saline solution, and between 200 and 300 grams of feces. All 6 had the FMT by way of enema but one had it administered by colonoscope in addition to enema. All reported that they found a donor right away. One reported a delay of a few weeks while getting the sample tested. In the survey I forgot to ask if the donor sample was tested. The donor and sample should be tested: “In general, donors are excluded if they have taken antibiotics within the preceding 3 months; are on immunosuppressive or chemotherapeutic agents; have known or recent exposure to HIV; hepatitis B or C; have a current communicable disease; are morbidly obese; have IBD, IBS, atopy, chronic diarrhea or constipation; GI malignancy or polyposis; participate in high-risk sexual behaviors; use illicit drugs; have a history of recent incarceration or travel to areas with endemic diarrhea. Donor blood testing should be performed for HIV, hepatitis A, B and C; donor stool testing includes culture, C. difficile toxin, ova and parasites, Giardia antigen, cryptosporidium antigen and Helicobacter pylori antigen if the oral route is to be used” [17]. And in case you happened to miss it there’s an excellent FMT procedure outline and a complete donor screening outline in a recent article of Therapeutic Advances in Gastroenterology [18].

The ages of the donors: 61, 59, 47, 42, 40, and 35 years old. Everyone reported knowing information about the diet of the donor. It was an open-ended question and none of the donors had remarkable diets (remarkable would mean vegan, vegetarian, gluten free, food allergy, etc…). None of the donors had been on antibiotics in the previous 6 months.

When asked if their medications changed after FMT, 2 said yes and 4 said no. Half of the respondents used antibiotics in preparation for FMT.

Five of the six reported that FMT helped resolve IBD symptoms. In their own words:

MR: “Yes. After 3 infusions, my bowel was completely normal, and my energy levels were high. Symptoms came and went after that, but with diligent follow up infusions, I went from a health percentage of 75% to 95% by my estimation.”

AB: “Yes! I had a lot of inflammation and diarrhea which subsided within 24 hours of fmt”

HT: “Yes for a few days immediately after fmt my symptoms were clear but they slowly came back until I had the next fmt”

JG: “Only for the day or two following the treatment”

JB: “Cured C-diff, lessened symptoms greatly (no blood, strong decrease in nausea), ceased all medications except for maintenance mesalamine and VSL DS (imuran later added to maintain remission)”

One answered that the FMT made their symptoms worse. Here’s her thoughts: “I was flaring for over a year before I tried the FMT and wonder if the delicateness of my war-torn colon contributed to the FMT making my symptoms worse.”

My experience with the side effects of IBD medications is horrifying [19] so I made it a point to ask specifically about the side effects of FMT.

RM: “My symptoms got worse: more bleeding, more discomfort, less formed stools.”

MR: “Besides making me better? :)

AB: “Terrible bloating and pain, not so much from the transplant itself, but from the Imodium they gave me to hold the stool.”

HT: “None, felt good after them.”

JG: “Cramping”

JB: “None”

As a separate question I asked about long term side effects and none of the respondents expressed concern. Additionally I asked if their experience had been recorded in a clinical trial. There were 5 no’s and one yes (a trial at New York Presbyterian Hospital).

This is the breakdown of how many FMT treatments each received:

RM: 3

MR: More than 30

AB: 1

HT: 5

JG: 4 or 5

JB: 4

Interestingly, the person who had the most FMT’s gave the most glowing review of the procedure.

All but two reported they began to respond after one treatment. The exception is RM who reported that FMT made her worse and the other, MR, needed 3 treatments. In conclusion I asked what the downside of FMT is. Here are the answers:

RM: “The DIY approach was a gross, strange, uncomfortable process. If it would help, though, it would be worth it.”

MR: “That we don’t use it more regularly.”

AB: “No downsides whatsoever.”

HT: “Mixing the enema.”

JG: “Messy, smelly, time consuming.”

JB: “’ick’ factor for the general public, difficulty in finding and screening a donor for general public.”

That review paper I modeled most of the questions after came to the following conclusion: “Whilst the available evidence is limited and weak, it suggests that faecal microbiota transplantation has the potential to be an effective and safe treatment for IBD, at least when standard treatments have failed. Well-designed randomized controlled trials are required to investigate these findings”[14]. The paper reviewed 17 different articles which encompassed reports on 41 patients, 27 with UC, 12 with Crohn’s, and 2 unclassified. By contrast just using Crohnology we’ve found 6 patients, 3 with UC, 2 Crohn’s and one with IBS. The review article reports a reduction in IBD symptoms in 19 of 25 patients (76%). By contrast this study found 5 of 6 (83%) reported that FMT helped resolve IBD symptoms. But I don’t agree with “…when standard treatments have failed…”. If you’re a patient then the side effects matter. Because of its benign risk FMT should be a first line treatment for IBD. There are no reported cases of long term or even short term intolerable side effects. Yes, there’s a case of vomiting and few cases of fever and cramping. The data set for FMT used on IBD is small but when considering side effects we should include all those who’ve had the treatment for other reasons. There’s thousands who’ve used it for CDI. I’ve scoured the net for reports of adverse FMT events. I didn’t find anything remarkable, no deaths or even hospitalizations. I did however come across the video testimony of a 9 year old girl with UC named Emma who’s an FMT champion. I also don’t agree with the evidence being weak. It’s absolutely not. Compare for a moment the risk profile of FMT with the likes of azathioprine, prednisone, and the biologics. If FMT were a drug it would be marketed as a blockbuster. None of the biologics can claim the same success without harm that FMT can [20, 21, 22, 23]. There’s also a very serious transparency issues with the safety of biologics [24, 25] but this is a different issue which I promised, back in the opening paragraph, to ignore. IBD cases are complicated but it’s a clear choice for me about what treatment should be a priority and which should take a back seat. We, the patients, need to help physicians operate under the philosophy of first do no harm. The part in the conclusion regarding randomized control trials seems sane but I’m gonna fade that too. Using a placebo on an IBD flare is like using you’re kitchen’s fire extinguisher on a forest fire. Does anyone seriously consider a placebo cast for studying the best way to fix broken bones? But maybe I’m wrong and the IBD community could do well to put placebo poop up against the real deal. Though ambitious it seems like something we could potentially organize with the help of Crohnology. In the mean time there is plenty of patient data, testimonials, and observations to collect and organize. It will be used so share your story!

Raw Data File of Survey Results 

Note: This post has an addendum.

References:

[1] Thomas J. Borody, Sudarshan Paramsothy, Guarav Agrawal,  Fecal Microbiota Transplantation: Indications, Methods, Evidence, and Future Directions, Current Gastroenterology Reports 15:337 (2013).

[2] F. Zhang, et al., Should we standardize the 1,700-year-old fecal microbiota transplantation?, American Journal of Gastroenterology 107, 1755-1766 (2012).

[3] Lawrence J. Brandt, et al., Long term follow-up of colonoscopic fecal microbiota transplant for recurrent Clostridium difficile infection, American Journal of Gastroenterology 107, 1079-1087 (2012).

[4] Lawrence J. Brandt, Fecal Transplantation for the Treatment of Clostridium difficile Infection, Gastroenterology and Hepatology 8, 191-194 (2012).

[5] Thomas J. Borody, and Alexander Khoruts, Fecal microbiota transplantation and emerging applications, Nature Reviews Gastroenterology and Hepatology 9, 88-96 (2012).

[6] Daniel K. Podolsky, Inflammatory Bowel Disease, New England Journal of Medicine 347, 417-429 (2002)

[7] Kevin J. Maloy, and Fiona Powrie, Intestinal homeostasis and its breakdown in inflammatory bowel disease, Nature 474, 298-306 (2011).

[8] Junjie Qin, et al., A human gut microbial gene catalogue established by metagenomic sequencing, Nature 464, 59-65 (2010).

[9] Kenneth S. Spriggs, What Was Your Crohn’s Misdiagnosed As?, www.diyehr.com, (2011).

[10] Crohn’s Disease, Wikipedia: The Free Encyclopedia, [accessed 10 September 2013].

[11] Thomas J. Borody, et al., Bowel-flora alteration: a potential cure for inflammatory bowel disease and irritable bowel syndrome?, Medical Journal of Australia 150, 604 (1989).

[12] Kenneth S. Spriggs, Crohn’s Disease Case Story in a Nutshell, www.diyehr.com, (2013).

[13] Kenneth S. Spriggs, Revising My Life on Drugs with Medical Lifeline, www.diyehr.com (2011).

[14] J.L. Anderson, et al., Systematic review: faecal microbiota transplantation in the management of inflammatory bowel disease, Alimentary Pharmacology and Therapeutics 36, 503-516 (2012).

[15] Kenneth S. Spriggs, Help From a Family Practice, www.diyehr.com (2011).

[16] B. Eiseman, W. Silen, and G.S. Bascom, Fecal enema as an adjunct in the treatment of pseudomembranous enterocolitis, Surgery 44, 854-859 (1958).

[17] Lawrence J. Brandt, and Olga C. Aroniadis, Fecal Microbiota Transplantation Past Present and Future, Current Opinion in Gastroenterology 29, 79-84 (2013).

[18] Faith Rohlke, and Neil Stollman, Fecal Microbiota Transplantation in relapsing Clostridium difficile infection, Therapeutic Advances in Gastroenterology 5(6), 403-420 (2012).

[19] Kenneth S. Spriggs, My Drug Induced Psychosis, www.diyehr.com (2011).

[20] Jennifer L. Seminerio, et al., Infliximab for Crohn’s Disease: The First 500 Patients Followed Up Through 2009, Digestive Diseases and Science 58, 797-806 (2012).

[21] Jean-Frederic Colombel, et al., Adalimumab for Maintenance of Clinical Response and Remission in Patients With Crohn’s Disease: The CHARM Trial, Gastroenterology 132, 52-65 (2007).

[22] Gary R. Lichtenstein, Remo Panaccione, and Gordon Mallarkey, Efficacy and Safety of adalimumab in Crohn’s Disease, Therapeutic Advances in Gastroenterology 1(1), 43-50 (2008).

[23] W.J. Sandborn, et al., Adalimumab for maintenance treatment of Crohn’s disease: results of the CLASSIC II trial, Gut 56, 1232-1239 (2007).

[24] David Healy and Harriet Rosenberg, AbbVie: Humira Timeline, www.davidhealy.org, (2013).

[25] David Healy, AbbVie Petition: Drug hazards are not trade secrets, www.davidhealy.org, (2013).

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