The Texas Medical Center at Houston is the world’s largest medical complex and home to some of the most advanced and innovative medical treatments available. It is surprising then that in the heart of this medical technology complex patients are receiving a low-tech treatment option that is more than 90% effective at curing their disease.
The treatment is known as fecal microbial transplantation (FMT) a procedure in which fecal matter, or stool, is collected from a tested donor, mixed with a saline or other solution, strained, and placed in a patient, usually by colonoscopy, to replenish the patient’s population of ‘good’ bacteria throughout the colon.
Through a collaborative partnership between St. Luke’s and The University of Texas School of Public Health (UTSPH), led by Dr. Herbert DuPont, MD, MACP, Director of the Center for Infectious Diseases, UTSPH, FMT has been made available by colonoscopy to approved patients participating in a clinical trial since 2013. Recently, Dr. DuPont and his team started a new clinical trial that is assessing the effectiveness of FMT when administered by non-invasive methods that include enteric coated capsules.
This week, Dr. DuPont took the time to speak with me about their new clinical trial and what he thinks the future of FMT will be over the next decade.
Dr. DuPont, thank you for agreeing to speak with me. The first FMT trial at St. Luke’s started in 2013 with very favorable results, and now you and your team are conducting another trial that is using a less invasive method of delivery. Can you talk a little about the results you have observed and how you see FMT’s role in the future, specifically, how will it best be used for treating patients?
There are a number of diseases associated with dysbiosis, which means the intestinal material has lost its diversity. The analogy that I use is that the intestinal bacteria look like a Persian carpet with tens of thousands of species of bacteria that form little interlocking walls to keep microbes that may cause mischief in the gut from producing — kind of walling them off. Well, when people get courses of antibiotics the diversity of these bacteria is depleted, and instead of a Persian carpet, it is a carpet with one or two colors in it, and now C.diff can swim everywhere and disease can occur — the most pure model of dysbiosis is recurrent C.diff infection. So, this is the model to test FMT methods. In a patient with recurrent C.diff, if we put bacteria isolated from a healthy person in the colon by colonoscopy it has a 90% cure rate, and if you take the 10% failures and give them another donor product, you can essentially cure them all. Now we know that you can put these bacteria in the colon, you can give an enema, or you can put the FMT in the duodenum, the upper small bowel, through a nasoduodenal tube that tells you that oral use of the drug will work because if you have enteric coated capsules it’s essentially the same as the nasoduodenal tube. So, oral delivery should work and enema has been shown to work before. So study 2 is to take frozen FMT and administer it by enema or lyophilized (freeze dried) material given orally in capsules and that is what we are doing right now with patients in the study taking the oral capsules.
The first study we did which started almost two years ago in 2013, was designed to test it through the colonoscope using fresh frozen and lyophilized material to see if they were comparable in efficacy and they were. The value of that is frozen works and we have shown it now — and Emory, as well as University of Minnesota have shown it — then you can stockpile bacteria and treat all 2000 patients in Texas every year that have this condition of recurrent C.diff. If the lyophilized works, then we should be able to make capsules and that has led into study number 2: frozen by enema that a nurse can give with no GI doctors involved, very cheap and low-tech; or pills, enteric coated capsules that can be released in the upper small bowel rather than in the stomach, since stomach acid could cause problems.
How is the trial 2 going?
We have 8 patients on it and it looks like it is going well.
Are you seeing better results with the non-invasive method?
We don’t have enough experience in study 2 yet to know.
Patients that have undergone the FMT procedure often times call it a ‘miracle,’ so what if anything are the Food and Drug Administration (FDA), the medical establishment, and insurance companies doing to make this procedure more readily available to patients?
It is a miracle!
Each one of those entities is different:
The FDA had a meeting in May of 2013 and the issue — they are required by Federal Law to test any product that is going to be evaluated for therapy — of having an IND, (Investigational New Drug) application, well after this meeting they decided C.diff was such a critical problem and FMT was so successful they wouldn’t require an IND — they were essentially breaking the law. So the FDA is bending over backwards to allow this to be used- and that is a great story!
Now, why isn’t it more available? Why are we the only full service program in Texas? That has to do with economics. [The program itself] is very expensive. The most expensive part is screening the donors looking for all those diseases infections and illnesses — each one of those tests has a cost, to screen a donor is something like $875. So, consider that when you develop a program. The other thing is reimbursement is not very good. So the reasons why centers are not developing are that it is not cost-effective — you will end up spending money not making money. So, it is not a surprise that private doctors don’t want to develop this. We do it here because making money is not what we are after — we receive no money from the FMT — we just basically get enough money from the subjects to pay for the expenses, but we are in it for research and that is why we have an advantage over groups that are involved with fee-for-service activities.
Now as far as the 3rd part of your question about the payers: why don’t they recognize this. I think it is conservatism with payers — unless it is an approved indication, they don’t really approve off-label things even if there is evidence for it because it gets chaotic. Their view has been if it is approved by the Federal Government and FDA they will pay for it. If it is not, it is research. Now while I understand their view I think they could look at the data and see that a patient who is taking years of very expensive antibiotics that cost about $3500 for 10 days for one drug and $1400 for 10 days for another, and these patients are on these drugs month after month after month, the economics is quite clear. So some of the payers have bought this and do pay for FMT if it is done by colonoscopy, but we find that they are not going to pay for the pill or the enema part because that is more investigational and we don’t know if it is going to work. So we know that we are not going to get reimbursed by insurance companies going into this.
Is CMS (Centers for Medicare & Medicaid Services) an entity that reimburses?
It does not. It will pay for the colonoscopy but not for FMT.
That is surprising considering the number of occurrences of chronic C.diff in Nursing Homes?
Once the FDA approves it then they will pay for it.
Now once the FDA does approve FMT in the future do you see this as one day being an over the counter (OTC) treatment?
It will be an OTC if organized properly. For example, it could be put in fleet enema products. But most likely it will be a prescription based product. There is an important point being that FMT is a short-term solution. Ten years from now we will not be doing FMT — we will have isolated the active portion and will know what it is that improves this diversity of flora and we are developing animal models to help us identify what fraction of the FMT is active and within 10 years we will have the active components of this and we can administer that and stools will be gone. So that is where we are headed and once we have this modern generation probiotic then anything is possible when treating people.
Such as antibiotic resistance?
It is possible it could be important in antibiotic resistance but there are many potential applications as we said, including obesity, which would be an incredible thing!
You mentioned Parkinson’s disease: is the neurological community getting on board?
They know about this. We might do studies with Parkinson’s disease in the future.
Can you go into the link with Parkinson’s disease?
It has been associated with this dysbiosis — the colonic bacteria — these diverse Persian carpets of the bacteria communicate with the brain through small molecules that are able to cross the blood brain barrier such as cytokines and interferons, and peptides, which are in constant communication and the gut controls more of the immune system of the body than any other organ and there is this direct connection with the brain. So gut disease is associated with depression and anxiety, and these flora may well be involved in the chronic neurologic picture in some way. We don’t know how, but we know if you look at Parkinson’s patients their flora is abnormally noncomplex — it lacks diversity. So since the flora are so powerful it may be one approach — I don’t think it would necessarily cure Parkinson’s disease but it could help with the management.
So a question that the general public has is: “if FMT is reestablishing healthy flora in the gut, why can’t the probiotics they buy at the health food store, do the same thing?”
Do you know how they pick probiotics to sell? There is no science. They just pick a bug that is not pathogenic and market it and if you look at the health food stores there are no health claims — no claims — pick up a probiotic — it doesn’t claim to do anything. And there is no reason to think those probiotics on those shelves have any health benefits — no evidence for that — there are a few probiotics that have anti-C.diff activities, there is a combination VSL3 that has been shown to have benefit in IBS treatment but that is about it. It is an explosion industry with no scientific backing. Why don’t they make health claims? Why don’t they do studies? Why don’t they show that it works? Why don’t they get the FDA to approve their product’s use: because they are not really that effective?
Now if you want the best probiotic in the world — feed your bacteria and you got it! Much of the processed foods in the US are absorbed in the upper intestine and never get down to the colonic bacteria, but there are some foods that will make sure you have the healthiest flora possible and to list a few: bran, beans, oats, soybeans, flax seeds, bananas, avocados, root vegetables: onions, carrots, beets. Those foods are not absorbed by the upper gut and go down to feed the colonic bacteria in the intestine. So if you feed your bacteria and you avoid antibiotics you have the best probiotic available.
That is such the opposite of what we do in Western Culture.
Because we overuse antibiotics and we don’t have healthy diets. It is a horrible thing.
There have been instances reported of patients suffering from C.diff taking it upon themselves to perform FMT at home using a blender — how can the medical community prevent this?
You can’t prevent this because until FMT is readily available you can’t prevent that. There are actually instructions on the internet how to do that using a blender to mix up the stool and then administer it by enema, of course your blender is destroyed, and you are putting stool in and not bacteria but it works. I first did this in 1970 and I did grind up stool and put it in a patient; that was 8 years before we even heard of C.diff.
What made you want to try that procedure?
Well, the first studies were in 1958 when 5 or 6 patients with antibiotic hospital associated severe diarrhea were treated and cured. I had a patient when I was on the faculty at the University of Maryland, who was dying from antibiotic associated diarrhea — we didn’t know what C.diff was, but antibiotic associated diarrhea was well known. So I talked to leaders at the hospital and medical school into letting me give him a fecal transplant and it cured the patient.
In closing, is there anything else you think our readers should know about the study and FMT?
I will end with an image: A patient who was one of our early FMT study participants who sent us a picture at Christmas 2014 where she is holding this little baby up and looking straight into the eyes and she said “Thank you, thank you, thank you, for the first time in a year I can hold my grandchild.”
This is an amazing, low-tech, powerful thing, it is not monoclonal antibodies, surgery, modern drugs that kill this cell, this is just simple physiologic treatment. It is amazing!
If people are interested in becoming donors what should they do?
Contact us. We would love it. We do need them to give us a lot of samples because we have to screen them and we want to collect as many stools as we can to treat patients before we have to recheck them to make sure they haven’t gotten a new infection. We would love to have a few more donors!
If you are interested in becoming a donor or have more question about FMT contact: St. Luke’s FMT program at 832-355-4122