Fecal Microbiota Transplant Questions and Answers

Question 1:  What are the main requirements to be a good Fecal Transplant Donor?

Health: I suggest the Fecal Microbiota Transplantation Workgroup criteria as the baseline for determining a good donor. That means no infectious disease, autoimmune disease, gastrointestinal disease, atopic disease, blood sugar dysregulation, mood disorders, or chronic pain, and lab tests showing the donor to be negative for blood and fecal transmissible pathogens. I’ve had patients decide to skip the lab tests when they’re using a parent, child, or spouse as a donor and they feel confident that they don’t have risk factors for any of the things the lab tests look for. In addition, you’re looking for someone who has a formed bowel movement every day or almost every day, and who hasn’t had antibiotics in at least 3-6 months. Ideally you want a donor who has generally clear skin, healthy energy and activity levels, and a good disposition.

Age: Conventional wisdom is that kid colon flora resembles adult flora by age two, and that colon flora diversity declines in elderly populations, so the best donors will probably be between the age of two and sixty-five. That being said, I’ve seen people benefit when using FMT donors younger than two, and there’s no evidence (just speculation) that individuals over the age of sixty-five won’t make effective donors.

Family members: I’ve seen people with Ulcerative Colitis, C diff colitis, and other conditions benefit from family member donors and unrelated donors. No clear evidence yet, but my guess is that it doesn’t make a difference.

Blood type: There’s one paper (http://www.biomedcentral.com/content/pdf/1471-2180-12-94.pdf) suggesting that people who have blood type “B” or “AB” may have a significantly different gut microbiome than people who don’t, so in my practice I’ve recently started trying to pair donors and patients with compatible blood types, but it’s way too early to see if that’s making any difference.

Age is really an unknown, but clearly infants are ‘different’ from adolescents and adults, who are typically used, although more by convention than based on science. Likewise, family members are often used as they are willing confidantes, but whether that’s more effective is unknown. Intimate partners are generally the most desirable, in that if they do have an undiagnosed potentially transmissable infection, they’ve essentially already shared it, and it’s quite unlikely that a transplant exposes the recipient to any additional risk.

Question 2:  When treating C-difficile, how many and at what intervals are fecal transplants necessary?

There was a great meta-analysis (http://cid.oxfordjournals.org/content/53/10/994.long) that tried to answer that question. This chart (http://cid.oxfordjournals.org/content/53/10/994/T2.expansion.html) from that paper indicates that groups that gave one infusion saw an 81.7% resolution without relapse rate. Groups that gave two or three infusions had a 91.2% resolution without relapse rate. Groups that gave more than three infusions had an 87.2% resolution without relapse rate.

The way I use that information clinically with C diff colitis patient is to give an initial FMT infusion, and check in 24 hours later. If someone is 95-100% better, I tell them they’re done. If they’re less than 95% better, we do a second infusion, and check in again after 24 hours. I’ve had to administer as many as five infusions that way.

Extensive data supports that one transplant is sufficient (and effective) in the large majority of C diff patients. There’s no data (but probably no need for such data) on multiple transplants in this population. Most series have used a single implant, from a single donor, most often an intimate partner, with ‘cure’ rates of >90%.

Question 3:  What is the most effective way to deliver a fecal transplant? (Colonoscopy, enema, endoscopy etc..?)

Great question. The comparison chart (http://cid.oxfordjournals.org/content/53/10/994/T2.expansion.html) from the meta-analysis I mentioned in the previous question does it’s best to answer that question as well, and enema came up as he most effective technique! I want to emphasize here that the whole meta-analysis only looked at 317 patients, so I’m not convinced that enema-delivered FMT really is tremendously more effective for C diff colitis than colonoscopically-delivered FMT is, but it certainly doesn’t seem LESS effective.

Since I’m writing these answers for “IhaveUC.com” though, I want to address efficacy for UC. This question has never been examined, since there are so few people treating UC with FMT. The main doc providing FMT for UC is Thomas Borody, an Australian gastroenterologist, and he uses a colonoscope; he only published about his findings in 2003/2004, at which time he reported a 50% effectiveness rate, although he’s told me he’s seeing FMT be effective for UC about 90% of the time now. In my practice, I’m seeing no benefit in about 10% of UC patients, partial benefit in 60-70%, and complete effectiveness (no symptoms no meds, and eating a varied diet) about 25% of the time. That’s not nearly as good as Dr. Borody is reporting, and I wonder if it’s because we are reporting our successes differently or because he is administering via colonoscope.

I’ve seen complete turnarounds of UC (people with 10+ bloody BMs/day, some people with UC for decades) using enema-delivered FMT, but I wonder if some of my patients who improved partially (symptom free as long as they avoid certain foods or stay on certain meds, or off meds and eating a varied diet with most symptoms gone, but still experiencing at least one symptom) might have improved more with colonoscopically-delivered FMT, so I’m training in colonoscopy, and hope to be able to offer it to patients in summer of 2013, although it might be longer than that.

Also not definitively known, and there’s plenty of data supporting quite high cure rates with all three routes. Clearly, as a gastroenterologist, colonoscopic administration is available to me, and intellectually makes sense. Upper tract administration (NG tube or endoscopy) seems to have modestly lower cure rates in a global (not statistical) analysis, and is esthetically unappealing to many, as well as potentially exposing the infusate to acid, bile salts, pancreatic enzymes etc, which could have unknown effects. Enema cure rates seem quite reasonable as well. To a man with a hammer…..

Question 4:  Can fecal transplants work for people who have a j-Pouch?

There aren’t any cases in the published scientific literature of using FMT for people with a J-pouch, and I haven’t used FMT anyone with a J-pouch in my practice either. However, since pouchitis can respond to oral probiotics (http://www.ncbi.nlm.nih.gov/pubmed/12730861?dopt=Abstract), it seems likely that changing the pouch microbiome with FMT has potential to benefit people with recurrent pouchitis.

 

unknown (to me, at least)

 

Question 5:  Is it recommended to take antibiotics prior to starting fecal transplant therapy?

Another great question. Dr. Borody. who’s the most experienced doc in the world at using FMT for UC, gives antibiotics before FMT for every UC patient. The idea makes sense: try to decrease the amounts potentially harmful bacteria we don’t want in there so they are more easily outcompeted by the healthy bacteria that we’re introducing with FMT. Since Dr. Borody uses them for all his patients though, I didn’t know before I got started how important of an ingredient that was to the success of his FMT infusions. I’ve prescribed Dr. Borody’s protocol (metronidazole, vancomycin and rifampin) to some of my UC patients before FMT, used different anti-biotic pretreatment protocols for others, tried herbal antimicrobials with some, and used no antimicrobial pretreatment with about half of the UC patients I’ve tried FMT with. I’ve seen successes and failures in each of these groups, and although I haven’t carefully analyzed my own clinical data yet, I don’t think I’m seeing more success in the antibiotic pre-treatment group.

There aren’t any studies that have looked at this in humans, but there is one group (http://genome.cshlp.org/content/20/10/1411.long) who has studied this in rats: they did FMT with a number of rats, and used a very accurate DNA-measuring technique to look at their colon flora before and after the treatment, while comparing it to the colon flora of their donors. They also gave half of the rats antibiotics first. They concluded that “antibiotic pretreatment counter-intuitively interferes with the establishment of an exogenous community.”

In my practice I’m willing to prescribe the antibiotic pretreatment (since it’s part of the world’s most respected protocol) but I encourage people to consider trying it without the antibiotics, since of course those have some risks of their own.

 

I don’t believe so, although there are many opinions on same, and little data.

 

Question 6:  How effective are fecal transplants for helping patients treat Ulcerative Colitis and Crohn’s Disease?

Dr. Borody initially reported a 50% success rate in using FMT for a mixed IBD and IBS population ( PDF File Link to this study), and more recently has told me in conversation that he’s seeing complete resolution in 90% of the UC patients that he uses FMT with, as long as they are able to re-infuse for long enough. In my own practice (treating about 40 UC patients with FMT in the past year) I’m seeing no benefit in about 10% of UC patients, partial benefit in 60-70%, and complete effectiveness (no symptoms no meds, and eating a varied diet) about 25% of the time.

For Crohn’s, a lot less is known. Dr. Borody has reported using FMT with one patient with Crohn’s colitis, who became symptom free without meds or dietary restrictions for 18 months, then relapsed. I treated one patient with Crohn’s who had previously had most of his colon and parts of his small intestine resected. He did not see any benefit from FMT.

 

Also still very limited and early data. It’s certainly plausible that they might be, but as compared with the data for c diff, which to me is conclusive, this is still a very unsettled question.

 

Question 7:  What might be some of the reasons that Fecal Transplants work for some people and not for others?

That is the million dollar question. I don’t know. For some people, maybe their colon bacteria are not the primary trigger of their autoimmune colon inflammation, and FMT will never work for them. Other people may be using a non-compatible donor. For people that it could work for but hasn’t, I’m starting to think more and more that persistence is the key, just frequency of infusions until symptoms are well-managed, then gradually tapering. Some people who don’t benefit when trying FMT without pre-treatment via enema may benefit with antibiotic pre-treatment or or colonoscopic delivery.

 

host biome? donor biome? technique? moon phase? (ie, who knows)

 

Question 8:  What are some of the risks involved with trying Fecal Transplant Therapy?

I always tell people that the major literature reviews on the subject call the side effect profile of enema-delivered FMT from a properly-screened donor “none” or “negligible.” That being said, FMT isn’t approved by the FDA for any indication, and the biggest review to date has only included 317 patients, so there’s a lot we don’t know. FMT delivered by naso-gastric tube or colonoscope carries the small but real risk of perforation, peritonitis, or bad reaction to anesthesia. There are a list of health problems we associate with colon flora that currently make us exclude donors (asthma, eczema, IBS, colon cancer, any autoimmune disease) but it could be possible that there are other conditions we don’t know to exclude that are associated with gut flora, and that could be transmitted.

We haven’t really seen much morbidity or harm, but it’s still early, and still unknown. There is certainly a theoretical risk of infection transmission (Hepatitis C, for example, has been transmitted via colonoscopy, ostensibly a much lower viral load), although I’m unaware of any reports to date. Also, we’ve really got no clue how durable the ‘biome transformation’ is, and if it is durable, could that have adverse immunologic or metabolic consequences? it absolutely could, but we just can’t tell yet.

Question 9:  What costs might a patient expect to incur if insurance did not cover Fecal Transplant Therapy?

If they live with an eligible donor, and they are willing and able to do the preparation and administration themselves, it can cost under $100 for a blender, some enema bottles, a strainer, etc. If they want colonoscopic delivery (from Dr. Lawrence Brandt in New York or Dr. Alister George in California), it’s just the cost of the colonoscopy, which I think is a thousand or two.

If someone with C diff colitis does not have a donor, Dr. Alex Khoruts in Minnesota and myself (Mark Davis in Oregon) maintain fecal slurry donor banks form pre-screened donors. I also use my donor bank to treat patients with UC. People with UC who use my donor bank and are able to self-administer the enemas pay $4,050 for ten days, plus $200 per infusion for re-infusions if they are indicated.

 

Very variable. the procedure itself costs might be minimal for enemas, certainly higher for colonoscopy. The costs of donor screening can be substantial as well. the disposable blender from target is the least of it!

Question 10:  I have dysbiosis of the large bowel and chronic SIBO in the small intestine. Would a fecal transplant help rectify the colonic bacteria in both the small and large intestine?

Great question! I used to tell people routinely that I didn’t think FMT could help SIBO or other dysbioses of the small bowel. Now that I’ve started having some success treating patients with chronic constipation though, I’m realizing that sometimes SIBO can occur as a RESULT of large bowel constipation and other dysbiosis, and once you clear up what’s going on in the large bowel, you can see small bowel problems resolve as well.

 

completely unknown

 

Question 11:  If you tested positive for C-diff, would you first take antibiotics to treat the C-diff, or would you opt to try fecal transplant therapy first?

I personally would definitely try FMT first. Most docs who use FMT for C diff keep their patients on doses of antibiotics large enough to keep them sypmtom-free until they infuse the fecal slurries, but I did treat one patient who was not on any antibiotics at the time who had a complete resolution after FMT.

Certainly the national standard of care is currently first to take antibiotics, and apply transplant to multiply-recurrent patients. SHOULD that be the standard? Would i personally do differently? At this point, I think it is a rational and data supported standard, and no, I probably wouldn’t personally try transplant first.

 

Question 12:  Is the medical community expecting for fecal transplant therapy to become more popular and accepted as a viable option for more GI related health problem? (Besides C-diff)

Yes! The main reason that many gastroenterologists are not routinely performing FMT is that their hospital or clinic administrators will not allow them to perform a procedure that has not been shown to be safe and effective in a randomized controlled trial. There are currently two trials of FMT for UC underway, one in Toronto for Canadian adults with UC (http://clinicaltrials.gov/ct2/show/NCT01545908) and the other in Michigan for children with colonic IBD (http://clinicaltrials.gov/ct2/show/NCT01560819?term=NCT01560819&rank=1). The trial for adults is giving one enema-administered infusion per week for six weeks, and the trial for children is giving five infusions within the span of ten days. Now, neither of these duration/frequency protocols is what I would have chosen, but I’m hoping they see positive results, because if they do I expect to see many more gastroenterologists in the US and world-wide performing FMT for UC.

 

Absolutely. Huge buzz from this and the human biome project. all that’s left to figure out is, you know, well, who, what, why, when and how? ie EVERYTHING! it’s an exciting early stage and it will be fascinating to me to see how this all evolves over the next decade.

 

Question 13:  Additional Comments/Ideas regarding Fecal Stool Transplants…

I’ve been exploring some other untested ideas, some drawn from Dr. Borody, some from the naturopathic community. Sometimes I recommend a short course of prednisone just before and during the infusions period, and I usually recommend DHEA with prednisone. For UC patients I usually suggest a period of low to no fibre before starting FMT, then introduce fiber foods starting with the infusions. If people are using antibiotics or other antimicrobials I suggest using a bifilm disruptor–I most often use NAC.

 

 

 

 

Bright Medicine Clinic

Dr. Mark Davis
5432 N Maryland Ave
Portland Oregon 97217
phone 971.800.1368
fax 971.239.1913
info@brightmedicineclinic.com
www.probioticinfusion.com

 

 

 

Neil Stollman MD, AGAF, FACP, FACG
Chairman, Department of Medicine
Alta Bates Summit Medical Center
Oakland, CA
Associate Clinical Professor of Medicine
Division of Gastroenterology
University of California San Francisco
www.norcalgi.com

 

 

(On behalf of the iHaveUC readers and Colitis Patients of the world, I’d like to send a Huge Thank You to Dr. Davis and Dr. Neil Stollman for taking so much time to answer all of the user submitted questions.  And to everyone reading, please note that Dr. Davis volunteered his time for this Q&A session and has received no monetary compensation from the iHaveUC.com site.  Dr. Davis wrote another informational story on the site back in November of 2011 which you can also read via this link:  Fecal Transplant Info which has quite a few comments and additional answers.

Also, just so everyone knows, Dr. Neil Stollman is my personal GI doctor – and an amazing person too.  I’ve written about him before, and he appeared on the video I shot a few months ago sharing my colonoscopy results.  I can’t thank him enough for participating here as well.  Like Dr. Davis, he has received no monetary compensation from the iHaveUC site for his time and effort in participating with this Fecal Q&A project.)

Like always, please feel free to leave your comments below, and feel free to share or forward this valuable information to anyone else who might have questions about this type of therapy.  Thank you as well to everyone who submitted your questions.  I tried my hardest to include all of your questions that I felt would benefit as many people as possible, however there were some very specific questions that some of you wrote which were not included (and I apologize for that).  If that was one of you, post your questions in the comment area below with the hope that an answer will follow.

-Adam Scheuer

PS: here is a video which might answer some more of your questions that you still may.  It focuses specifically on Fecal Transplant Therapy for C-Difficile:

Update Recent News (as of January 2013): And if you just really have not gotten enough about Fecal Transplants and C-DIFF, there’s some more news about the effectiveness here in a new “Fecal Transplant Microbiome Breakthrough Study“