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I can still remember where I was standing when I first heard of fecal transplants. It was the fall of 2009, and I was in my fourth year in the naturopathic medicine program at National College of Natural Medicine (NCNM) in Portland, Oregon. As a student, I interned with Dr. Steven Sandberg-Lewis, a naturopathic doctor with over 30 years of experience treating patients with inflammatory bowel disease (IBD). His patients were often very sick people who had failed many or all pharmaceutical interventions, or were only stable on strong doses of prednisone, and I helped manage their care.
We used diet, herbs, nutritional supplements, and other interventions, and many of our IBD patients improved, some quite dramatically. For those who continued to suffer, I scoured the literature, researching everything from traditional world medicines to cutting-edge discoveries, and one day, standing in the hallway at a computer kiosk at NCNM, I came across Thomas Borody's 2003 paper "Treatment of Ulcerative Colitis Using Fecal Bacteriotherapy."1
Borody is an Australian gastroenterologist who has been using fecal transplants for patients with IBD since 1989, when his Centre for Digestive Diseases reported on using the technique with 55 patients with irritable bowel syndrome (IBS) or IBD.2 His paper took my breath away. The six ulcerative colitis (UC) patients whom the 2003 paper described reminded me of my own UC patients: frequent bloody stools, pain, weight loss, anemia, and, most importantly, nonresponsive to most or all other therapies.
His patients became asymptomatic, they came off medications, their lab values normalized, and eventually colonoscopy revealed normal tissues with all traces of inflammation gone. He followed one patient as long as 13 years, and at his last colonoscopy there was no sign that the patient had ever had UC. Borody called the process "human probiotic infusions," a name that I love, but since then the name fecal microbiota transplantation (FMT) has become more standard.3
The treatment seemed simple enough – dilute fresh stool (from a screened donor) with normal saline, filter, and administer the liquid, teeming with healthy bacteria, as a retention enema. Borody applied "anticlostridial" antibiotics and oral bowel lavage beforehand to reduce the endogenous bacterial population, and suggested a high-fiber diet afterwards, to feed the new bacteria.
Standing there in that hallway, it felt like I had found a silver bullet. I remember thinking, "This could be so powerful, and it sounds so simple!" As I reflect on FMT now, 5 years later, I continue to be floored by what a powerful tool it has been, but it is not always simple, and it certainly isn't a silver bullet for everyone with UC.
FMT is the process of administering microorganisms from the stool of a healthy donor to a patient's GI tract. Coprophagy is an important biological trait in some animal species, and the oral administration of stool from healthy human donors to human patients with intractable diarrhea has been reported since the 4th century in China, through the 16th century in China and Europe and in modern times.4–7 FMT was first documented in modern medical literature by Eiseman et al. in 1958, who reported using FMT retention enemas with four patients with infectious colitis, three of whom were very close to death.8 All four recovered completely within 48 hours following FMT retention enemas. After Eiseman, there are sporadic reports of FMT for pseudomembranous colitis and other forms of Clostridium difficile infection (CDI) for a few decades, and then, in 1989, two reports of FMT for IBD. One is the report by Borody, in which he describes treating 55 patients with IBD and IBS. The other is a letter from American physician J. D. Bennet, whose own UC had been steroid dependent for 6 years until a series of FMT retention enemas reversed his disease.9
Over the past 5 years, interest in the microbiome, and in fecal transplant in particular, has skyrocketed. FMT continues to appear safe and quickly curative for adults, children, and immunocompromised individuals with refractory CDI.10–12 There have been no serious side effects conclusively associated with FMT in hundreds of published case reports. FMT also appears to be safe, and effective to varying degrees for children and adults with IBD. 13,14
How does FMT accomplish all this? Analysis of patient fecal microbiomes after FMT shows that they more closely resemble the donor's microbiome than the patient's own pre-FMT microbiome.15 Unlike aerobic Lactobacillus and Bifidobacterium probiotics, which are typically transient organisms, the anaerobic colon organisms of FMT appear to effectively colonize and inhabit the colon. They may help banish C. difficile by taking over the same niche and simply outcompeting it. Or, it may be that antibiotics produced by the donor colon microbes are sufficiently lethal to the C. difficile organism.
Theories abound as to how FMT benefits patients with IBD, some of whom may get durable benefit from a single or limited series of infusions, some of whom may need "top-off" infusions to stay well, and some of whom to do not appear to respond at all. It may be that IBD is triggered or aggravated by the lack of important immunomodulating organisms such as Faecalibacterium prauznitzii that FMT replaces.16 It could be that FMT is outcompeting or killing bad actors in the native microbiome as we suspect it does with C. difficile. It could be that FMT simply restores a ratio, or triggers immunomodulating reactions in the same way that even heat-killed Lactobacillus and Bifidobacterium probiotics can.
More of the Story
The first patient whom I pitched FMT to was a 14-year-old male with a 6-month history of ulcerative colitis. The conversation went something like this:
Me: So, there's another therapy I'd like you to consider. It's called human probiotic infusion.
14-year-old: What is it?
Me: Well, the idea is that you might have some bacteria in your colon that are causing your immune system to react, or you might be missing some bacteria that normally quell inflammation. The bacteria in someone else's colon might be a better fit for you, so we collect stool from a healthy person, strain it, and give the part with the bacteria to you as an enema.
14-year-old: The therapy is giving me poop?
14-year-old: Well, that doesn't sound too bad. I guess I'll think about it. What's an enema?
Me: It's a tube that's lubricated and inserted through the anus into the rectum, then the HPI flows through the tube into the rectum.
14-year-old: Anus? Butt? My butt? You stick something into my butt? No way. Can't you just inject it into my veins or something?
Dr. Sandberg-Lewis: Actually, that would kill you.
That first patient did not take me up on my suggestion, in part because he was a 14-year-old boy, but also because he hadn't been living with ulcerative colitis for very long. When researchers at the University of Chicago asked a series of focus groups consisting of patients with UC and parents of children with UC how desperate they'd have to be to consider FMT as a therapy, they were nearly unanimous: not only would they be interested in trying it, they'd like to have it available as a first-line therapy, before they tried immunosuppressants.17 As one patient in my practice says, "People who don't have inflammatory bowel talk about 'the yuck factor' of FMT. They have no idea – the yuck of FMT pales in comparison to the yuck of living with this disease every day."
Before I started my private practice in 2011, I had worked with exactly one patient with FMT. Laurie was 37 years old at the time, with a 4-year history of UC, and mother of twin toddlers. Her first round of five FMT retention enemas didn't benefit her at all. Two months later, she wanted to try again, so we tweaked everything: different donor, different timing, and a different support system that helped her retain the infusions for longer. This time, her UC improved – she described herself as 90% better. I was hooked.
The Question of Antibiotics
In 2011, there was, as far as I could tell, no one in the US offering FMT for inflammatory bowel disease and offering a donor bank, although there were a few medical doctors around the US and Canada regularly using it for CDI. I decided to make that my niche. I bought the website fecalmicrobiotatransplantation.com, and started spreading the word. I wrote articles, and gave talks for IBD support groups and CE talks for professionals.18–20 The FDA had not yet regulated FMT, so I was treating patients with CDI, IBS, chronic constipation, microscopic colitis, ulcerative colitis, Crohn's disease, and occasionally other autoimmune or inflammatory diseases.
Early in my career, I had the opportunity to ask Borody some questions about FMT. He told me at that time that he had never had a patient decline the antibiotic pretreatment part of his protocol. Without any comparative data on the topic, I tell my patients that they can choose whether to use Borody's protocol or try FMT without antibiotic pretreatment. I work with patients who choose some combination of pharmaceutical and/or herbal antimicrobials and biofilm busters, and some who choose no pretreatment at all. Oral bowel lavage can leave patients with too much bowel laxity to retain the fecal slurry enema for the 6 hours that I recommend, so I often use large-volume water cleansing enemas about an hour before FMT instead. I'm often using other interventions alongside FMT, offering guidance on diet, and supplements tailored to the individual.
My favorite quote about medicine is from Hippocrates: "Life is short, and the art is long. Opportunity is fleeting, experimenting is dangerous, and deciding is difficult." It can be hard, as a clinician, to feel confident about which interventions have made a difference for your patient. That being said, my experience leads me to believe that some people with IBD can have near-miraculous benefit from FMT without any antibiotics involved. I also suspect that there are some people with IBD who will not see any benefit from FMT unless there are antibiotics on board beforehand.
Several of my IBD patients have not benefited from an initial round of FMT, then completed a course of Borody-style antibiotics followed by a second round of FMT and then benefitted. However, in the spirit of avoiding the post hoc, ergo propter hoc fallacy, let me return to Laurie, the 37-year-old with UC and twins. Her first round of FMT did not benefit her, but a second round of FMT, also without antibiotics, benefited her substantially. Perhaps my other patients who did a second round of FMT with antibiotics may have just been benefiting from a second round of FMT.
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