Fecal Microbiota Transplantation for Inflammatory Bowel Disease Part III

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Fecal Transplants put my ulcerative colitis in remission in 1 week.

Before going into the results, let me first tell you the circumstance I was in. Prior to my first fecal transplantation, I was in a 6 month long flare. During these 6 months, I was coming at this flare with everything I knew to do, in both the conventional and alternative medicine realm. I sought out help from a nationally known integrative medicine MD, a very good gastroenterologist and an excellent primary care doctor. In spite of all this support, I was still not well.

I tried diet, food sensitivities testing, comprehensive stool analysis testing, herbs, vitamins, probiotics, antimicrobials, LDN, prednisone (steroids) and Asacol. Don’t get me wrong, all these therapies helped, but weren’t enough to push me over the edge of being in remission and able to come off of prescription steroids. I was clearly a difficult case.

All good physicians know that taking prescription cortico-steroids for any longer than a few weeks is a bad thing for the patient because of the negative short and long term side effects.

At any attempt to lower my dose of prednisone (steroid) below 10 MG all of my ulcerative colitis symptoms would come back with a vengeance. Being steroid dependent is nerve racking. Conventional medicine treats steroid dependence by weaning the patient on to the next higher class of drugs, the powerful immune suppressers and hope that they work in place of the steroids. If the higher classes of drugs do not work, you are looking at surgery. I was opposed to taking these dangerous immune suppressors, you can read about why in FMT part 1.

Fecal transplants were the last thing that I was going to attempt before giving in and using the immune suppressing drugs and I am glad I did.

Three days before my first FMT, I had a colonoscopy. The scope showed mild to moderate pan-colitis with small bouts of inflammation scattered throughout my colon; this was in spite of still being on prescription steroids. The biopsies from the colonoscopy said:

“Surprisingly biopsies from your entire colon showed inflammatory changes. This was even in the upper colon where it looked totally normal.”

I planned the scope before I started FMT so I could quantify how much the procedure helped. I have not had another colonoscopy after FMT in light of preserving the new bacteria in my gut after FMT but I do plan on comparing before and after stool tests for beneficial bacteria.

Week 1 of FMT

The day after my first FMT I was having completely normal bowel movements. Three days into FMT I was able to taper completely off of steroids without a recurrence of my symptoms.

Ever since my diagnosis of UC, my gut was noisy, gassy, border line painful, and irregular at times even when in remission. After FMT my bowels were quiet, non-tender, regular and predictable. I would go entire days and not even think about my colon because there weren’t any symptoms present to remind me that my colon was functioning sub-optimally.

I began to realize that what I considered “normal” in terms of digestion was not actually normal at all; it was just my interpretation of what normal was having come from a place of much worse digestion (UC flares). After FMT I was reminded of what normal healthy digestion felt like. The kind of digestion people have that is truly healthy and literally forget that their colon is a part of their body because it always does what it’s supposed to.

For 6 blissful months I remained in this place of perfect digestion. I was beginning to ask myself “is it is possible that the FMTs had somehow eradicated a pathogen in my gut and now I’m cured”?

Somewhere around month 7, life kicked in. Stress from college which lead to more studying and less sleep lead to the presence of ulcerative colitis symptoms. While the symptoms were mild, it was enough to indicate that fecal transplants do not work for me forever.

For whatever reason, the positive effects gleaned from FMT appear to have an expiration date for me. I have found that if I do 1-3 weeks of fecal transplants every 6 months then I can retain the positive effects. I’m currently working on strategies to prolong the benefits so I don’t have to continue FMT forever. That being said, for many, prolonged FMTs may be a viable option.

I clearly benefited from fecal transplants. The question in my mind is if this is a viable treatment for other individuals with inflammatory bowel disease? If so, is it accessible?

To answer this question I dug deeper into the literature on FMT for inflammatory bowel disease. Below I will sum up a total of 6 popular studies using FMT for inflammatory bowel disease.

If you are not interested in the details of the studies scroll on down to my thoughts on FMTs for my interpretation of the current FMT research.

Best Study Outcomes in UC

Study 1 Study 2
Method The first FMT transcolonoscopically followed by daily enemas for 14 days, then second daily, X3 per week, X2 per week and ultimately weekly at each step for a period determined by clinical response with a colonoscopic review at 12 weeks but without a bowel lavage to preserve the therapeutic microbial luminal contents. Fecal flora donors were healthy adults who were extensively screened for parasites and bacterial pathogens. Patients were prepared with antibiotics and oral polyethylene glycol lavage. Fecal suspensions were administered as retention enemas within 10 minutes of preparation and the process repeated daily for 5 days.
Results This study reported a 91.9% response rate to FMT with 67.7% achieving complete clinical remission after FMT, defined as a 0–1 score on a modified Powell–Tuck Index; 24.2% achieved partial remission (defined as a ≥2 point decrease) and only 8% were non-responders.In 12 of the 21 (57%) patients who had a repeat colonoscopy performed (mean follow-up time 33 months; range 1–198 months), normal mucosa was documented with absence of histological inflammation. By 1 week post-HPI some symptoms of UC had improved. Complete reversal of symptoms was achieved in all patients by 4 months post-HPI, by which time all other UC medications had been ceased. At 1 to 13 years post-HPI and without any UC medication, there was no clinical, colonoscopic, or histologic evidence of UC in any patient.
Pros Very High remission and long term in follow up group All participants achieved sustained clinical remission.
Cons Retrospective study meaning only past or historical data was obtained. It is a small case series study meaning no placebo group, exposures maybe inaccurate, relationship between exposure and outcome cannot always be ascertained.
Study Borody T, Wettstein A, Campbell J, et al. Fecal microbiota transplantation in ulcerative colitis: review of 24 years experience [abstract]. Am J Gastroenterol 2012; 107 (S1):S665The largest series documenting FMT for ulcerative colitis. Treatment of Ulcerative Colitis Using Fecal Bacteriotherapy

 

Okay study outcomes In UC

Study 3 Study 4 Study 5
Methods Participants were examined by flexible sigmoidoscopy when the study began and then were randomly assigned to groups that received FMT (50 ml, via enema, from healthy anonymous donors; n=38) or placebo (50 ml water enema; n=37) once weekly for 6 weeks. Patients, clinicians, and investigators were blinded to the groups. The primary outcome was remission of UC, defined as a Mayo score ≤ 2 with an endoscopic Mayo score of 0, at week 7. Patients provided stool samples when the study began and during each week of FMT for microbiome analysis.First the window of time from the collection to the processing was 5 hours.
Second the amount used for every implant was 50 grams and was mixed with 300 mL of “commercial bottled drinking water”The solution was mixed with a plastic spatula and then filtered with a paper filter.
The resulting solution was then used fresh or frozen al -20 C, the authors make no mention of the addition of any anti-freeze solutions. Then 50 mL of the solution was inserted via enema and the patient has to retain it for 20 minutes.
a small phase 1 pediatric trial of FMT in 10 children and young adults with mild–moderate ulcerative colitis using five consecutive daily infusions Systematic review followed Cochrane and PRISMA recommendations. Nine electronic databases were searched in addition to hand searching and contacting experts. Inclusion criteria were reports (RCT, nonrandomised trials, case series and case reports) of FMT in patients with IBD
Results Seventy patients completed the trial (3 dropped out from the placebo group and 2 from the FMT group). Nine patients who received FMT (24%) and 2 who received placebo (5%) were in remission at 7 weeks (a statistically significant difference in risk of 17%; 95% confidence interval, 2%-33%). Seven of the 9 patients in remission after FMT received fecal material from a single donor. Three of the 4 patients with UC ≤1 year entered remission, compared to 6/34 of those with UC > 1 year (P=.04 Fisher’s exact test). Stool from patients receiving FMT had greater microbial diversity, compared with baseline, than that of patients given the placebo (P=.02, Mann Whitney U test).  33% achieved clinical remission at the end of 1 week and 78% had a clinical response, with 67% maintaining a clinical response at 4 weeks.  In patients treated for their IBD, the majority experienced a reduction of symptoms (19/25) 76%, cessation of IBD medications (13/17)76% and disease remission (15/24) 63 %. 
Pros Very elaborate well designed study. Almost 90% of the patients that responded to FMTs remained in remission after 12 months.  Good clinical response  Reduction in symptoms of most 
Cons Only 24 % were in remission by the end of the study, did not measure the clinical response. FMT were only preformed once a week. Small Pilot study  Some of the participants in this systematic review were case studies. Not the highest remission rates 
Study Fecal Microbiota Transplantation Induces Remission in Patients With Active Ulcerative Colitis in a Randomized Controlled Trail Safety, tolerability, and clinical response after fecal transplantation, in children and young adults with ulcerative colitis.   Systematic review: faecal microbiota transplantation in the management of inflammatory bowel disease
Comments There was a clear benefit from implanting stools from one donor over the other one, meaning it is possible that some the donors stool maybe more potent at reducing symptoms than others. The researchers noted a slight trend for frozen-thawed stool to be more efficient than fresh stool     

 

Crohns Disease

Method rifaximin 200 mg 3 times daily for 3 days until the evening before procedure. Study participant recipients also received omeprazole (1 mg/kg orally) on the day before and morning of the procedure. Transplant recipients also received 1 capful of MiraLAX in 8 oz of water 3 times a day for 2 days. A nasogastric (NG) tube was placed for transplant, and location was confirmed by x-ray. Approximately 30 g of donor stool was mixed with 100 to 200 mL of normal saline and blended with a commercial blender (Hamilton Beach Personal Blender, Southern Pines, NC) at low speed for 2 to 4 minutes until a homogenous texture was achieved. The stool was then filtered twice using 4 × 4 gauze. Infusion was slowly administered through NG tube over a 3-minute period. The NG tube was flushed with 15 mL of normal saline over 1 minute. After 15 minutes, the NG tube was removed. 
Results Two weeks after FMT, 7 of the 9 patients were in clinical remission based on PCDAI scoring. At 6 and 12 weeks, 5 of 9 patients who did not receive additional therapy were still in remission. 
Pros High rates of clinical remission.
Cons Small study
Study Fecal Microbiota Transplant Effect on Clinical Outcomes and Fecal Microbiome in Active Crohns Disease

My Thoughts on Fecal Transplant Research

The message that can be pulled from the chart above is that there seems to be a large variety of outcomes in different studies. The study outcomes range from 100% clinical remission rates to only 24% clinical remission rates.

What can explain such a large mixed result in these studies?

To answer this question, we must first take a step back and ask, is there one perfect microbiome for everyone? We don’t know the answer to this question just yet. The perfect micobiome for one person may be completely different for another person. This too may explain the variety of outcomes. (1)

Researchers have noted that the selection of individual stool donors appears to be important. “The efficacy of this approach may also be donor dependent and this may explain why some case series have shown promise and others have had disappointing results.” (2)

I think one thing that is forgotten is how multivariate the microbiome is. Diet, stress, environment, sleep, exercise all affect the microbiome and the microbiome of the individual donors.

Fortunately, this understanding of the microbiome and new treatments aimed at modulating the microbiota should perpetuate the holistic or ecological approach to medicine and treating complex diseases in approaching them with a multifactorial notion in mind. It brings diet back into the conversation, because you cannot separate the microbiota from the diet.

In western medicine we tend to have a reductionist view that a single agent is the cause of a disease. This has been largely perpetuated by the germ theory, the germ theory states that some diseases are caused by a single microorganism. While this theory may be appropriate for communicable diseases, the non-communicable western diseases are rarely that simple and neglecting the fact that there are multiple variables at play in these diseases is a large problem we see in the research today.

You begin to see this reductionist, germ theory inspired notion of medicine in the studies on fecal transplants as if one factor will determine the efficacy of the fecal transplants.

One study that is taking place in Texas on the efficacy of fecal transplants for patients with IBD did so by administering only one single dose fecal transplant and observing its effects. (3)

Why would researchers only administer 1 dose of fecal transplants and expect to see result in IBD? The single dose fecal transplants work well for treating patients with C diff, however, it is well known by most clinicians and researchers specializing in this area, that IBD requires multiple administrations to show a positive clinical response.

Researchers believe the length of time the patient has had the disease appears to play an important role as well. “FMT may be more efficacious in patients with a recent diagnosis of UC, and this is biologically plausible, as a perturbation in the microbiome might be more easily restored early in the course of the disease,” (4)

Other factors that are often not considered by FMT researchers

  • Did the recipient take the antibiotics before the study?
  • The diet of the recipient
  • Is the recipient on proton pump inhibitors? (5)
  • Does the recipient have small intestine bacterial overgrowth (SIBO)?
  • Does the recipient have food sensitivities or gluten intolerance?
  • Does the recipient have a chronic infection?
  • Does the recipient have nutrient imbalances such as low vitamin D?
  • Does the recipient have current inflammation?
  • Does the donor have to pass a comprehensive donor exclusion criteria evaluation?

You begin to see all the different moving parts one must at least consider before drawing conclusions on microbiome research.

All of these factors effect, and are effected by the microbiota. Observers that reduce a study down to a single exposure: “does the patient get fecal transplant yes or no”? And drawing a reductionist conclusion without considering other variables that impact the outcome of the study, may be a reason why we see such a large discrepancy in fecal transplant research.

There are clearly some methodological errors in some of these FMT studies. But there are some important pearls that can be pulled from fecal transplant research.

What may increase likelihood of FMT success?

“You have to treat the whole of the patient, not just the hole of the patient” (6)

 

  1. Heal intestinal permeability and inflammation BEFORE FMT

FMT appears to work best if the gut isn’t actively inflamed; using whatever it takes to get the inflammation under control prior to FMT should contribute to a higher likelihood of success.

One study found that using fecal transplants in people with moderate to severely active ulcerative colitis actually increased the systemic immune response by increasing the C reactive Protein (a marker of immune activity). (7)

One potential mechanism as to why this may be happening is that when the gut is actively inflamed as in IBD, the tight junctions in the digestive tract are damaged and allowing the passage of the bacteria in the gut and entering into the rest of the body where the bacteria shouldn’t be (bacterial translocation) thus provoking an immune reaction on bacteria that normally resides in the gut. This phenomenon is called intestinal permeability (AKA leaky gut).

Intestinal permeability appears, in part to be a result of an altered intestinal microbiota which leads to the breakdown of the gut barrier. That being said, other things also contribute to intestinal permeability such as NSAID use. (8)

Temporary use of IBD directed pharmaceuticals can help decrease intestinal permeability and inflammation prior to fecal transplants as well. If your symptoms are bad it may be a good idea to use steroids to calm things down prior to starting FMT. I can’t emphasize enough how important it is to utilize all the tools available in conventional and alternative medicine to calm down your digestive symptoms prior to FMT. I find that many individuals involved in integrative medicine/holistic health often have a bias towards avoiding all pharmaceuticals (even the safe and effective ones) but they can be extremely helpful in the short term. Note: I did not attempt to lower my dose of prednisone until I began seeing improvements while using fecal transplants.

In FMT part 2 I discuss other methods to induce intestinal healing prior to fecal transplants with the use of diet, vitamins, and herbs.

I believe that keeping my inflammation levels manageable with drugs, diet, vitamins, and herbs had a positive outcome on my success with FMT.

Studies have shown that poor diet can induce intestinal permeability. Which brings me to the next point. (9)

  1. Diet

For many, diet alone is enough to control their digestive symptoms. Common problematic foods that should be eliminated are: gluten, sugar and possibly dairy and eggs. (10) Emphasis should be placed on increasing intake of fermentable carbohydrates such as listed below. These foods will likely have to be introduced very slowly and one at a time:

  • Legumes (resistant starch, fiber): beans and lentils if you tolerate
  • Starchy tubers (resistant starch, fiber): sweet potatoes, cooled white potatoes, cooled rice, plantains, green bananas, peas etc.
  • Prebiotic rich foods: Onions, garlic, leeks, shallots, asparagus, artichoke, chicory root, dandelion greens,
  • Raw nuts and seeds.

It may be wise to get the inflammation under control before adding fiber rich and prebiotic foods in the diet. Many clinics that perform fecal transplants counsel patients to follow a low fiber diet before FMT treatment and subsequently follow a high fiber diet after treatment.

If you have not first tried switching to a real food diet like paleo, SCD or GAPS then you probably shouldn’t bother with FMT. If you continue to eat the same poor diet that contributed to the gut dysfunction in the first place, then there is no reason to do FMT, as in theory you will not retain the results.

Microbiome researcher Jeff Leach made the statement “one thing that I learned very quickly is I can shift my gut microbiota in a very short time. The single macronutrient that seem to have the greatest impact on my personal microbiome is dietary fiber”.

Diet is a less drastic way to nudge your microbiome in a positive direction and decrease intestinal permeability (leaky gut) without going through all the trouble of fecal transplants.

  1. Chronic infections and dysbiosis

Intestinal dysbiosis is an imbalance of microbial communities in the gut, more specifically an overgrowth of bad bacteria and an undergrowth of good bacteria. Dysbiosis is strongly associated with IBD. (11) Fecal transplants work by correcting this dysbiosis. Ensuring that your digestive illness is dysbiosis related often requires testing.

Metametrixs GI effects and Doctors Data comprehensive stool analysis can detect levels of disbiosis. I used the metametrixs GI effects 2200.

These tests can also rule out infections, parasites and yeast. If you have a chronic infection, it’s quite likely that fecal transplants will not work for you unless the infection has first been addressed so testing is important.

Frequent antibiotic use in the past, C section birth and not being breast fed are all risk factors of intestinal dysbiosis. Those who respond positively to antimicrobial therapy maybe an indicator that manipulation of the microbiota is helpful. An example of this is when IBD patients improve from taking gut directed antibiotics.

  1. Length of the FMT procedures

It appears that the more FMTs the better the results. This is supported by the literature too:

“It seems that although initial FMT may not immediately cure UC, as happens with CDI, over many months to years, the implanted microbiota appears to progressively transform the inflamed UC mucosa to normal, histologically uninflamed mucosa.” (12)

At the centers for Digestive Diseases, doctor Borody uses a long trial of fecal transplants using a slow step down fashion to taper the patients off of fecal transplants slowly. “Noting that ulcerative colitis requires multiple FMT infusions, such patients are now treated in CDD with the first FMT transcolonoscopically followed by daily enemas for 14 days, then second daily, X3 per week, X2 per week and ultimately weekly at each step for a period determined by clinical response with a colonoscopic review at 12 weeks but without a bowel lavage to preserve the therapeutic microbial luminal contents”. (13)

Notice how the length of time may vary from patient to patient.

Note: As I mentioned earlier I have found that if I do 1-3 weeks of fecal transplants every 6 months than I can retain the positive effects. Doing fecal transplants does appear to have an additive effect, meaning the results of every round I do seems to give me longer positive effects.

  1. Antibiotics prior to FMT

It has been my observation that the studies that achieved the highest remission rate of IBD received the most aggressive antibiotic treatment prior. Dr Borody at the center for digestive diseases uses 3 powerful antibiotics prior to fecal transplants: vancomycin (500 mg twice daily), metronidazole (400 mg twice daily), and rifampicin (150 mg twice daily), all by mouth for 7-10 days). (14)

Bacteria are competitive, and also produce antimicrobial peptides to protect themselves from other bacteria. The reason the antibiotics prior to FMT are necessary is to lower the amount of harmful bacteria so the protective bacteria can survive and thrive after the fecal transplant.

I did not use all 3 of these antibiotics prior to fecal transplants but I did use the metrondazole (flagyl) and natural antibiotics in addition that you can read about in FMT part II.

  1. A healthy donor

Healthy donors can be hard to find but are very important. I had written off this procedure because of failure to find an appropriate donor until I decided to start writing up a family tree.

Factors to consider when choosing a healthy donor:

  • The diet of the donor
  • Was the donor breast fed?
  • Was the donor born vaginally or C section?
  • If the donor used antibiotics within 3-6 months.
  • Did the donor grow up on a farm or in the city?
  • Does the donor exercise?
  • Does the donor get 7-8 hours of sleep?
  • Does the donor have healthy bowel habits?
  • History of illness: Depression, anxiety, Eczema, Asthma, Chronic fatigue, Food allergies, Psoriasis, Arthritis, IBS, HIV/Aids, Intestinal parasites, MS, complexion issues, atopic disease, neurodevelopmental, psychiatric or learning disorder, Obesity, insulin resistance, metabolic syndrome, lupus, frequent yeast infections, type 1 or 2 diabetes, multiple sclerosis and chronic pain.

Here is a donor exclusion form provided by the power of poop website.

I used a relative as a donor. He is 16 years old, really healthy, no acne, skinny, athletic, and has very little use of anitbiotics etc. He doesn’t eat perfect but he does eat some fruit and veggies each day.

Some scientists argue that it is better to use non family members as donor, as often times the individuals gut microbiota is already similar to his relatives from spending time around them.

Some clinics that offer FMT have donor stool banks that screen for healthy donors.

Another option for finding a healthy donor is to use a stool bank like openbiome that has a very strict donor criteria.

 Finding a doctor to work with

First, this is very important, find a doctor to work on this. If you present FMT to them respectfully and responsibly then they should work with you. It may be a good idea to print off a few of the studies, or this post on FMT and bring it to your doctor. I have found primary care doctors tend to be more open minded than specialists. Integrative medicine doctors (not a health coach) will be even more likely to be open minded towards this approach.

DO NOT attempt FMT without a tested donor.      

I used RDS Infusions in florda. The doctor I teamed up with was Dr. Shepard. He is very experienced in fecal transplants.

Unless you have C diff, in the United States doctors are only allowed to assist you with screening your donor for do it yourself fecal transplants and advise you on the procedure. This means that you will be collecting your donors stool, mixing it with saline, straining it and putting it in an enema bag. This is what I did. You can watch videos on it here and here.

In many ways it can be a somewhat less risky procedure when done with an enema, as it does not necessitate any of the risks associated with a colonoscopy. Some studies have shown that fecal transplants using an enema bottle may be the most effective delivery method. (15)

You can find a list of FMT providers here.

Is it safe?

If there are major side effects of properly done fecal transplants, they have yet to emerge. (16) One small study involving 10 children and young adults reported “No serious adverse events were noted. Mild (cramping, fullness, flatulence, bloating, diarrhea, and blood in stool) to moderate (fever) adverse events were self-limiting.” (17)

A double blind, placebo controlled study of 70 people found that “There was no significant difference in adverse events between ether groups”. (18)

One caveat to the safety of this procedure is having the donor tested. There have been case reports of individuals using untested donors and acquiring infections from them. Some individuals carry asymptomatic parasites unbeknownst to them. When this infected stool is transmitted from one person to another it causes major problems to an already impaired gut. This is why I cannot stress enough of the importance of testing a stool donor prior to the procedure.

Conclusion

Perhaps the most important thing that FMT taught me is the important role of the gut microbiota in ulcerative colitis and giving me empowerment over my disease. I now know that my disease responds positively to the manipulation of the microbioita. This nugget of information will change my life and the way I choose to cater my treatment. This doesn’t mean that everyone’s IBD will benefit from this procedure (as represented in the literature above). More and more I am seeing that it is not a quick fix, but more of a tool (a very powerful one). I don’t believe there is a quick fix for autoimmunity; it is a complex multifactorial disease with many moving parts.

A determining factor of success with FMT is likely contributed to sleep, stress management, exercise, addressing nutritional deficiencies, chronic infections, food sensitivities/intolerances and genetics.

 

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