Taking the Yuck Out of Microbiome Medicine

I can still remember the shock I felt when I heard about fecal microbiota transplants for the first time. It is not the sort of thing you forget.

At a microbiology conference, a scientist was giving a lecture about the microbiome–the microbes that live harmlessly inside of us. She described one unusual case she was involved in where a doctor named Alexander Khoruts used the microbiome to save a patient’s life. The patient had taken antibiotics for a lung infection. While the drugs cleared that infection, they  also disrupted the ecology of her gut, allowing a life-threatening species of bacteria called Clostridium difficile to take over. The pathogen was causing horrific levels of diarrhea. Khoruts couldn’t stop it, because it was resistant to every antibiotic he tried.

So Khoruts decided to use an obscure method: the fecal transplant. He took some stool from the patient’s husband, mixed it with water, and delivered it to her large intestines like a suppository. In a matter of days she was recovering.

Since I first heard about these transplants in 2010, they’ve hit the big time. Last year, a team of Danish and Finnish doctors reported clinical trials in which the transplants 94 percent effective against C. difficile. It appears that some species in the transplant from a healthy gut will grow quickly and outcompete the pathogen, returning a sick person’s intestines to its former state. Scientists have been exploring using fecal transplants for other disorders of the gut, along with conditions beyond the gut, such as diabetes and obesity.

But there are many obstacles left to putting fecal transplants into widespread practice. For one thing, the FDA is very cautious with this kind of living medicine. For another thing, fecal transplants are conceptually crude. Doctors simply give a patient a random sample of hundreds of different species from a healthy person’s gut, assuming that at least some of them will restore the patient to health. When the patients get better, they can’t say precisely why.

And then there is the yuck factor. In 2012, scientists conducting a survey about attitudes towards feccal transplants, politely summed up the problem this way: “patients recognize the inherently unappealing nature of FMT.”

But now there’s a potentially promising development in the quest to harness the microbiome. At an American Gastroenterological Association conference in Chicago this weekend, researchers will be describing how they cured C. difficile not with a fecal transplant, but with a pill full of bacterial spores.

The pill is the work of a small Boston-area company called Seres Health. They came up with a combination of certain harmless microbe species that naturally live in our gut. These species  all form spores, which are rugged enough to survive inside a pill. Once they reach the warm refuge of the gut, they pop out of their spores and multiply. In previous studies, Seres researchers showed they could treat C. difficile infection effectively in mice and hamsters. (Technology Review described the company’s efforts in this article from last December.)

Recently, doctors at the Mayo Clinic, the Miriam Hospital in Providence, and Massachusetts General Hospital ran a clinical trial on people to see if the pills from Seres were safe and effective. They gave the pill to fifteen people. The results were striking: the overall cure rate was 100 percent. (The detailed abstract pdf is here.)

I contacted Khoruts to see what he thought of the study. “It looks very promising,” he told me.

But Khoruts also raised a few caveats. He pointed out that the authors excluded very sick patients from the study because of the risk of adverse events. So the 100 percent cure rate might be higher than it would be in the real world.

Khoruts also pointed out a few potential problems with taking a pill full of spores as opposed to getting stool from a donor. Scaling it up to industrial production will require making sure that the factory stocks don’t get contaminated by strains of bacteria that would harm patients, for example.

In those factory stocks, Khoruts pointed out, the microbes will continue to evolve and adapt to their surroundings. If they become too well adapted to life in a factory, they may not do as well inside of people’s bodies.

Nor does the initial report on these pills actually explain how these particular species are conquering C. difficile. I’m sure that the fifteen people who were cured of these awful bugs aren’t clamoring for a detailed  mechanistic explanation of what happened when they swallowed the pills.

But if scientists are going to rationally design microbiome treatments for a lot of different conditions, they’re going to have to open this microbial black box.


16 thoughts on “Taking the Yuck Out of Microbiome Medicine

  1. .
    We are More Microbe than Mammal.

    Our MicroBiome Bug Trail .. Wags Us.

    We are now in an Antibiotic Resistance Epidemic.

    When will our Medical’s prescribe Pre & Probiotics WITH Antibiotic Scripts ?

    Research shows that the MicroBiome NEVER Returns to normal after Anti’s …

    Until Host is No More ..

    OR aggressively ReSeeded …

    When fighting enviro allergies in Dog’s ( Doggy GOO ) or Humans ( GOOy CHEWy ) …

    The GUT’s Biome Must be Healthy

  2. It annoys me that people always bring up the “yuck” factor. Do you want to know what is really the “yuck” factor? It is bloody diarrhea many times a day. It is seeing your sickly wife in the hospital, thin and pale. It is hearing her moaning and crying in bed, sick with c diff.

    And people think a fecal transplant is “yucky”? Suck it up – there are many worse and disgusting things. There is nothing “yucky” about healing someone who is sick.

    What about surgery? Isn’t that “yucky”? Cutting open my wife and ripping out their colon? No, that’s totally fine, but fecal transplant is “yucky”? It’s a joke and people should stop saying it.

    [CZ: I hope my post doesn’t imply that I personally consider this transplant “yucky.” If I was hit with C. diff, I’d be yelling for a transplant! But every time I write about this and look at the responses in comment threads, on Twitter, etc., I’m struck by how strongly it repulses many people. People are even disgusted by the concept of this pill–someone on Twitter went so far as describing it (wrongly) as swallowing shit. It’s an open question how much this disgust will hinder research, or stop people from taking this treatment.

    And I also hope that with my headline I wasn’t giving the impression that the “yuck” factor is the only issue at play here. Pills might be better simply because they’d be more carefully prepared combinations of species, rather than the random zoo found in stool.]

  3. Microbiome optimization can be achieved through diet (SCD, GAPS, PALEO, WAHL’s) and lifestyle factors (stress management, responsible sun, exercise, sleep, overall toxin load reduction…). RUSH, UMass, Stanford, and Wahl’s Diet studies have demonstrated such, not to mention the loads of online anecdotal support. Some of these patients (UMass for instance) were very seriously ill IBD patients. I get that the masses are offered pharma instead of these options as a first pass due to physician limitations and the “standard of care” legal mandates. But gut healing dietary protocols are always worth a first try, and there is a lot of online support if one decides to integrate such. Cdiff may be one ailment that exceeds the ability of gut healing dietary/lifestyle management mainly due to excessive antibiotic use that wipes out that microbiome beneficial bacteria to the point of no return.

  4. Relative to the IBD-FMT study (and IBS-FMT study) presented at the 2014 James W. Freston Conference, wouldn’t it have been great if a significantly relevant number of patients were (post-FMT) placed on a gut healing protocol to ascertain ramifications? I wonder if the authors: Olga C. Aroniadis, Adam Greenberg, Corbett Shelton, Lawrence Brandt, and David M Pinn even realize the relevance?

  5. The therapeutic possibilities of fecal transplants as well as the pill are astounding. I’m following the topic with great interest.

    I can empathize with Mike’s comments above and fully agree. I do also want to back up the author and say that the mainstream world has a hard time embracing anything like this, so using words like “yuck” may help readers loosen up rather than shut down. We need to get people on board to understand how devastating antibiotic therapy is.

  6. I agree with Mike above, emphasis of the “Yuck” factor idea is part of what is making adaptation of fecal transplant difficult, even in situations where it ought to be obviously worth trying. Our medical establishment does have a tendency to think that “experimental” in extreme cases is ok, if it comes packaged as part of a pharmaceutical product development project, but not if it comes from less potentially patent-able sources. The problem now is not so much about what the mainstream world thinks, but rather that the medical establishment has put up barriers to the procedure when it is desired by patients and their families.

    I think that this information needs to be tied into the information in your previous column, The Quantified Microbiome Self. While using the pill is obviously a huge improvement, what happens next? Does it really return a patients intestines to their former state? Or do these much more benign that C-Diff, but still rugged (by design) microbes take over in a manner that shuts out a more balanced microbiome?

    If I were facing C-Diff today, I might be inclined to believe that fecal transplants from my husband might lead to a better mix for me, in my environment, than one out of a pill. Especially if the pill can not be guaranteed to have remained as advertised. And I might want to undergo several such transplants in series, on the theory that what got established first, in the disturbed state of a C-Diff infection, could be joined later by other species for an improved balance.

    Also, it seems to me that part of the ruggedness factor is due to the use of a pill, which is being “inserted” at the wrong end. If a synthetic microbe mixture is used, why wouldn’t it be placed, as a fecal transplant is, where it is actually needed?

  7. I have to agree with Mike: if I have a choice of dying of dehydration while on antibiotics that are working too slowly or not at all, or getting a fecal transplant with a very good chance of a cure–I will take the fecal transplant. At that point one doesn’t care about any psychological drawbacks.

    I was worried about using endoscopy to plant the new material, when my GI system was already devastated and sometimes bleeding. I was worried about finding a healthy donor (as I read one often has to do this for one’s self, using the old method).

    For those reasons, it’s maybe good the “pulsed” protocol with vancomycin worked, as the freeze-dried coated preparation was never widely available and the totally lab-prepared kind in your article here was not ready yet.

    But it took a long time for my gut to start healing, during which time I continued to struggle to eat and drink enough, and my GI system still is worse than before the infection (especially, more food sensitivities, to the point where I can no longer eat a balanced diet–my GI doc and my cardiologist support what I’m eating given the circumstances, but I am not happy with food avoidance as a long-term solution). Maybe this kind of microbe transplant would still be beneficial.

  8. It’s a long standing practice in animal husbandry to do this the direct way: when a sheep gets very ill and needs a heavy dose of antibiotics it is often necessary to repopulate the gut with familiar microbes as soon as possible. We do this by convincing the sick sheep to eat a small amount of manure from a healthy sheep. It’s easier said than dung.

  9. After the dentist prescribed Clindamyacin antibiotic in September, 2013 I battled c-diff until January because flagyl and Vancomycin compound only worked while taking them. Vancomycin compound is extremely expensive and insurance didn’t pay. My husband and I did a fecal transplant (he did all the dirty work). It was like a miracle, though I am wary of discontinuing daily yogurt and probiotic. This pill sounds wonderful if it happens again!!

  10. As I nurse who has taken care of many patients with C. Diff and seen people die in agony despite IV antibiotics and antibiotic enemas meant to cure the C. diff; I would gladly give myself an fecal enema or eat poop for that matter, rather than endure the days of horrible diarrhea, pain and body damage that occurs during this infection. So many times I’ve wished that fecal transplants were the first line of treatment rather than antibiotics.

  11. My son contracted cdiff when he was 17. He now has ulcerative cholitis and PCS. I think his health issues were caused by undiagnosed vitamin D deficiency. I had my teenage daughter checked, her Vitamin D level was so low, that the Dr called before we got home. She now takes supplements. If she were to get cdiff, I would want FMT done on her immediately. I hope this treatment will help prevent whatever causes people who get cdiff from developing other chronic diseases.

  12. I wondered about the pill image and figured out it’s just a photo used with attribution from a flickr photographer. I very much doubt the developers would choose a clear, brown color for an ingestible spore medicine (speaking of reducing the “yuck” factor).

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