Fecal Microbiota Transplantation for Inflammatory Bowel Disease Part II

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Healing gut barrier integrity prior to FMT

Fecal microbiota transplantation (FMT), is a procedure that extracts the stool bacteria from a tested healthy donor and implants the extracted bacteria into the colon of individuals with Clostridium difficile, ulcerative colitis, and crohns disease with much success in clinical trials. (1, 2)

I preformed this procedure on myself with the help of an overseeing physician and had amazing success with it. FMT essentially replaced my entire gut ecology with a new intact microbiota, replacing species that may have been extinct in my westernized microbiota.

I saw immediate results the first day I did 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. You can read about my success story here.

As described in fecal transplants part I, many of the diseases we face in this country are a product of our lifestyle and environment. Ulcerative colitis seems to be associated with the western diet and is virtually non-existent in more primitive cultures. Simply doing fecal microbiota transplants and expecting it to cure all your problems is probably very unlikely if you do not address all the other underlying perpetuating factors of your disease such as diet, sleep, stress, malabsorption, and food intolerances.

In spite of my eagerness to tell the world of my new found health I obtained from FMT, I wanted to first express the importance of covering all your bases before you begin a procedure such as FMT. This is why I wrote these posts in a series.

The Human Ecosystem

Attempting to manipulate the microbiome is complex; it brings a complex ecological approach to medicine and it is not always a black and white answer, which is quite possibly why adding a species or two, or eight particular probiotics may not have been very helpful for me in the past. (3) This may also explain why some individuals do not benefit in the long term from doing FMT.

In a paper I found in the journal nature, the authors compare manipulating the gut microbiota to lawn care. In this analogy, the antibiotics would be like an herbicide that wipes out the lawn. If the lawn is left alone undesirable weeds may grow or opportunistic bacteria (bad bacteria).

To get the lawn back on track, sowing grass seeds would be akin to taking a probiotic, additionally lawn food (fertilizer) would be similar to prebiotics (fibers that feed beneficial microbes). Alternatively it may be better to replace the lawn with new grass, this is akin to fecal transplants. (4)

If your yard was overrun with weeds, just throwing grass seeds on your yard would not take care of the weed problem, the same as just using FMT would not take care of the overgrowth of a pathogen, which ill explain later is associated with IBD.

It’s interesting to see that much of the research coming from the American gut project and the human microbiome suggests that the gut should be treated as a complex ecosystem.

This concept of treating the gut as an ecosystem aligns with the model that many alternative healthcare practitioners have used for years and this is the approach I used.

One example that comes to mind, that is common among alternative medicine practitioners who support treating the gut as an ecosystem, is the 4 Rs of gut restoration, or 4 R approach. The first of the 4 Rs is remove gut mucosal irritants such as pathogens, allergic foods, alcohol, medication and stress. The second R is replace agents essential for digestive functions, these include digestive enzymes and hydrochloric acid. The Third R is re-inoculate, with things like probiotics, fecal transplants, fiber and prebiotics. The fourth R is repair the mucosa lining, this can be achieved with nutrients, botanical’s and a couple pharmaceuticals I can think of. (4)

Interestingly enough Dr. Borody, the early pioneers of fecal transplants also used a similar approach while conducting his research on FMT.

Instead of just using fecal transplants in his patients with digestive disorders, he would first have them take a round of antibiotics to “remove” opportunist bacteria or pathogens. After the course of antibiotics he would then perform the fecal transplants (re-inoculate) on the patients. He would also encourage them to “re-inoculate” by educating them to eat more fiber. Not identical to the 4 R approach but you get the idea. (5)

Rather than trying to reinvent the wheel, I essentially followed a 4R approach prior, during, and after FMT while still following the instructions that the overseeing physician suggested I do.

Below I will list my Personal 4 R approach that I used to recover from ulcerative colitis in these exact steps.

Many of these I will list below are unconventional treatments, but the research is out there to support the use in these treatments of digestive disorders. I encourage you not to just take my word for it and do your own research; this is the reason I put live links to all the studies as a reference.

It is very important that you work with a doctor on this, preferably an integrative medicine doctor to oversee your treatment. These integrative therapies may be combined with conventional therapy as part of a comprehensive alternative treatment protocol.

1. Remove

As mentioned earlier the remove portion of this approach is to remove anything that could be irritating the intestinal epithelium (gut).

Diet

This includes food intolerance’s, food allergies, inflammatory foods, alcohol and NSAIDS. For many, diet alone is enough to put their digestive symptoms to rest.

As mentioned in Is Starch a necessary component for a healthy microbiotia, my concern with staying on SCD/strict paleo/starch free diet, while doing FMT, was that in the past it hasn’t done much of a job with providing enough substrates to feed beneficial bacteria, so I didn’t want to risk not providing enough diversity of fibers for the newly implanted bacteria to feed on, essentially starving my new microbiota.

My dietary restrictions are largely based on my test results from an IgG food sensitivities, associations in gluten intolerances and IBD, and a high risk of celiac disease according to a celiac panel. (6)

Anti-tissue transglutaminase antibodies are used as a marker to detect celiac disease. It just so happens that anti-tissue transglutaminase tends to be elevated in patients with IBD. (7) This means that individuals with IBD are especially at risk for gluten intolerance.

Dr. Fasanos’ research has demonstrated that exposure to gliadin, a component of gluten, appears to increase intestinal permeability (leaky gut) in everyone that consumes it, even healthy subjects. (8)

The point I’m trying to get across is the removal of gluten from the diet is the single most important dietary modification someone should make if they are suffering from any gastrointestinal disorder.

I essentially follow an auto immune paleo protocol (AIP). Dr. Sarah Ballantyne does a great job of describing the science and rationale for this protocol.

That being said, there is no one diet for all. Individual intolerance’s, food sensitivity tests, etc should serve as a guide to you in finding a diet that is appropriate for you. My diet looked something like below:

Emphasis on

  • Chicken broth
  • Beef broth
  • Fermented foods
  • coconut oil (caprylic acid, lauric acid)
  • Fresh ginger tea
  • Grass-fed/free range liver weekly
  • Dark leafy greens
  • Wild caught fish
  • Seaweed
  • Starchy tubers
  • Prebiotic foods
  • Mineral waters

Eliminated foods

  • Gluten, corn, oats etc.
  • Soy
  • Eggs (test came back very high on IgG food sensitivity)
  • Dairy, except ghee (high IgG food sensitivity)
  • Alcohol
  • Peanuts- are actually a misnomer, botanically they are actually not a true tree nut, they are more of a legume. What makes them bad is that unlike other legumes, it is not necessary to soak and or cook peanuts before you eat them. Soaking and cooking beans lowers the lectin and phytic acid content greatly.
  • Nightshades (I cheat on this one a lot; if I eat a lot of nightshades, I notice joint pain)
  • NSAIDS

Antimicrobials

It is also important to remove any pathogens that could be contributing to epithelial damage. Prescription antibiotics are commonly used by gastroenterologists to treat IBD flare and are helpful for inducing remission. (9) Antibiotics do manipulate the microbiota and appear to be beneficial in the short term, but they damage the microbiota by decreasing diversity and killing good commensal bacteria in the long term. Comparing it to the example used earlier, using antibiotics for gastrointestinal disorders is akin to knocking out undesirable weeds. After removing the weeds (pathogen) it is important to replace with seeds (probiotics, FMT).

I used both prescription and a natural antimicrobial before I did FMT. Listed below are my notes and research on possible reasons as to why antimicrobials are effective for IBD and why it’s important to use herbal antibiotics.

  • Gammaproteobacter is a class of bacteria that tends to be elevated in individuals with IBD. Gammaproteobacteria is a class of proteobacteria that we know to be mostly pathogenic organisms such as Salmonella (enteritis, typhoid fever), Vibrio cholerae (cholera), Yersinia pestis (plague), Pseudomonas aeruginosa, E.coli (food poisoning).
    • Escherichia coli tends to be higher in Crohns disease and ulcerative colitis; E coli is known to activate toll-like receptor 4 (TLR4) leading to an inflammatory cascade. TLR4 expression is already up-regulated in IBD. (10, 11, 12, 13)
    • E coli is a pathobiont meaning it is capable of causing disease, and may be a potential trigger for an IBD flare. This may explain the remitting and chronicity of IBD. (14)
  • Pathogenic E coli seems to induce intestinal inflammation in mice and seems very good at adhering to and invading intestinal tissue. (15)
  • This may also explain why antibiotics are sometimes effective in treating IBD.
  • Interestingly, a commercial probiotic that contains a friendly strain of E coli named E coli nissle 1917, goes by the brand name mutaflor, appears to be therapeutic in treating IBD. Rather than trying to eradicate E coli, it maybe more beneficial to crowd it out pathogenic E. coli with this friendly strain of E. coli. (16)
  • 5-amino salicylic acid (5ASA), a drug commonly used to treat IBD- the exact mechanism of this drug is unknown but it is thought to act as an antioxidant and decrease intestinal inflammation. 5ASA has been linked to reductions in Escherichia/Shigella genus. This may shed light on of the effect the immune system has on regulating the microbiota. A possible genetic predisposition to IBD, is regulating our microbiota negatively by limiting the type of bacteria that is able to survive. I know there are studies showing our microbiota regulates our immune system but it appears that an overzealous immune system may also regulate out microbiota. (17)
  • Patients with UC have elevations in sulfate-reducing deltaproteobacteria. : Deltaproteobacteria is a class (just below phylum level) of bacteria that are sulfur reducing bacteria, this means the bacteria derive their energy by reducing sulfur and produce hydrogen sulfide. Hydrogen sulfide is damaging to the intestinal epithelium. (18) This maybe one reason that patients with ulcerative colitis tend to have foul, rotten egg like, sulfer smelling flatulence.

To sum of the list above, pathobioant bacteria (proteobacteria such as E coli) appears to ignite IBD (damage the epithelium) and then flees the scene (becomes dormant).

Elevations in E coli are associated with IBD. E. coli and other pathogens, may act as a primary pathogen in the bowel triggering flares. Berberine, a herbal antimicrobial, has been shown to be effective against eradicating pathogenic E coli and Vibrio cholerae. Berberine also promotes recovery of IBD in animal models. (19, 20)

For this reason, I choose berberine as an antimicrobial.

Prior to FMT, I used both prescription and herbal antimicrobials and they really seemed to calm things down for me quite a bit. My success with both prescription and herbal antimicrobials has gotten me to see the importance of them in treating gut dysbiosis (imbalance of good and bad bacteria). Some of the most effective studies using FMT were done by Dr. Borody, who was a big proponent in using antibiotics before FMT. In fact, he uses three strong antibiotics prior to FMT. (21)

Antimicrobials I used:

  •  Berberine: A derivative of goldenseal, use 400-1000mg daily for 1 month (antimicrobial, anti-inflammatory, in animal models helped repair damage from ulcerative colitis, lowers TNF alpha, a common drug target for IBD drugs) (22)
  • Caprylic acid: (found in coconut oil, I took 1 to 2 tsp of coconut oil a day) 
  • Metronidazole: (flagyl, requires a prescription)

Biofilm disrupters

Biofilms are slimy protective structures that bacteria secrete to protect themselves. Biofilms are mesh like accumulations of extracellular polymeric substances. A good example of a biofilm is the plaque that is on your teeth.

Biofilms are often present in chronic and persistent infections. These biofilms are often so protective of the bacteria that the body’s defenses and antibiotics are often ineffective against them. (23)

In order for antimicrobials to work, it is important to break down bacterial biofilms. These are what I used to address this problem.

  • Lactoferrin: Found in colostrum, glycoprotein that starves bacteria by depriving it of iron.
  • NAC, N-acetyl-cysteine: reduces and prevents biofilm formation. (24)
  • Klare labs interface plus: breaks down pathogenic biofilms, contains a mixture of many different enzymes that break down bacterial cell walls. One good example is lysozyme, which targets gram positive bacterial cells peptidoglycan. (25)
  • Lauricidin: Monolaurin, an extract of lauric acid, a naturally occurring fat purified from coconut to increase therapeutic benefit. I’m not sure of the efficacy of this over coconut oil yet. I just used coconut oil. (26)

2. Replace

I grew up in a house hold where we consumed the flavored antacids like candy. At the time I was oblivious of the essential functions that stomach acid plays in digestion.

Prolonged use of proton pump inhibitors (acid blocking drugs) appear to produce bowel symptoms and increase small intestinal bacterial overgrowth (SIBO). SIBO is a condition of excessive bacteria in the small intestines.(27)

SIBO is associated with IBS, chronic diarrhea, weight loss and malabsorption.

Hypochlorhydria (low stomach acid) is a problem that can be treated by using betaine Hcl. This raises the acidity of your stomach and small intestine which discourages overgrowth of bacteria in places it shouldn’t be, like in SIBO.

Replacing stomach acid with betaine Hcl prior to meals, will also aid in digestion, adsorption of nutrients and prevent infections. I plan on writing more extensively on this topic later.

What I used:

  • Betaine Hcl: One study demonstrated that 1500mg of betaine Hcl acidified the stomach of individuals with PPI induced hypochlorhydia. (28)

3. Repair

There are quite a bit of herbal medicine and nutrients that help restore the intestinal epithelium, but I try to stick to the ones that have actual studies for their use in IBD.

  • Andrographis: One study demonstrated that in patients with mild to moderate ulcerative colitis, 1,800 mg daily of andrographis paniculata extract were more likely to achieve clinical response than those receiving placebo and had similar efficacy of mesalamine. (29)
  • Bosweillia serrate: Clinical remission of colitis was higher in bosweillia group than in placebo. (29)
  • Wormwood (Artemisia absinthium) : I must admit I have not tired this one but the evidence for it is compelling. In a study of crohns disease 65% of patients were in remission using wormwood compared to none in remission of the patients in the control group. Lowers TNF alpha. Appears to improve the mood of patients using it. (30, 31, 32)
  • NAG – (N-Acetyl Glucosamine): I found this on Centre for Digestive Diseases website, they are considering this as a potential therapy for IBD. One small study shows positive results in pediatric IBD patients. (33)
  • Phosphatidyl choline: a few human studies show that they may be helpful for UC. (34)
  • Fish oil EPA/DHA: Numerous studies show a reduction in disease activity in IBD. It appears to be more effective in ulcerative colitis than it is in crohns disease. (35)
  • Turmeric or curcumin: A natural inhibitor of the cytokine TNF-alpha, Curcumin phytosomes complexed with Phosphatidylcholine (BCM 95 or mervia) is much better absorbed. Works much like NSAIDS pain relieving effects from COX-2 (cycloxygenase-2) inhibition. (36) In one study of patients with mild to moderate ulcerative colitis, 53% receiving curcumin achieved clinical remission at 4 weeks compared to none in the placebo group. (37)
  • Zinc l carnosine: in a study of patients with active ulcerative colitis, 71% of patients using a zinc carnosine enema had a better clinical response or remission compared to 10% in the placebo group. (38)
  • Mesalamine (5-ASA): Requires a prescription, well tolerated drug for ulcerative colitis and Crohns disease. 15-20% of patients with mild to moderate UC treated with mesalamine achieved remission. It appears to reduce the chance of colorectal cancer. As mentioned earlier it is linked to reductions in E. coli. (39)
  • Low Dose Naltrexone (LDN): This is a very interesting drug and requires a prescription. Naltrexone was originally formulated to treat opioid addiction. When used at much lower doses (3-4.5MG) has been demonstrated to be helpful in treating a host of auto immune conditions. Very few side effects have been reported of this drug when taken at such low doses. It is believed to work by boosting endogenous opioid production and increasing T regulatory cell function. In a study of cohn’s disease, patients treated with LDN had a 78% decline in crohn’s disease endoscopy severity. (40)

4. Re-inoculate

There are 100 trillion in numbers and 10,000 individual strains of bacteria in the microbiota. More importantly, about 40% of the microbiome has not been cultured, this is what makes it such a hot topic in research. We are also finding that our guts may also harbor viruses and fungi that has no harmful effect. (41)

A 10 strain probiotic doing much good seemed like a drop in the bucket. We simply have not mapped out all the different bacteria present in the human gut. Learning about the complexities of the microbiome it quickly becomes evident that we are dealing with a diverse ecosystem.

Fecal Microbiota transplantation is currently the only method of completely replacing the vast array of diverse bacteria that is missing in many digestive disorders.

In my next post I will explain how I went about finding a healthy stool donor, having him tested and actually doing the procedure.

 

Further Reading:

Fecal Microbiota Transplantation for Inflammatory Bowel Disease Part III

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