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Results from a Faecal Microbiota Transplantation Phase-I Clinical Trial

Discussion in 'Research' started by joshualevy, Dec 27, 2020.

  1. joshualevy

    joshualevy Approved members

    Dec 30, 2008
    Faecal Microbiota Transplantation (FMT) is a surgical procedure where stool is transferred from a healthy donor into the gastrointestinal tract (usually the colon) of the patient. The standard use is to treat people whose gut microbiota has been decimated by antibiotic treatment or who have a runaway Clostridioides difficile infection (commonly called "C. diff"). The goal is to seed the regrowth of a healthy microbiota. This is sometimes called "bacteriotherapy" or "fecal transplant".

    Recently some researchers have thought that type 1 diabetes might be triggered or encouraged by something in the gut microbiota. I reviewed this theory (in the context of probiotics) a year ago:

    The DIMID1 Study

    This study enrolled 20 adults with T1D during their honeymoon phase (within 6 weeks of diagnosis). Half got transplants from healthy people, and half got transplants from themselves. Both groups went through the same procedures, but the second group got no new microbiota. Both groups got three procedures in the first four months, and were followed for a year. The exact times are marked with an arrow in the charts below. The primary results were C-peptide production (which measures the body's ability to generate insulin), and the secondary results were a wide variety of immunological, microbiota, and blood sugar control measurements.

    This study was funded by the AMC Hospital several Dutch organizations. It ran from 2013 to 2017 in the Netherlands. The researchers did not report on the ethnic composition of the participants.


    The primary results are summarized below. The blue lines represent the people who got the a transplant from a healthy (non-T1D) donor and the red represents people who got a transplant from themselves. These are all people in their honeymoon phase, and you can see the "transplant from healthy" group C-peptide numbers drop (as expected from an untreated group) but the "transplant from self" group stays steady, which is better than expected. After a year the "transplant from self" group has not gotten worse, but the "transplant from healthy" group has, and the difference is statistically significant. The "C" results are for fasting (sometimes called "baseline") C-peptide generation, while the "D" results are for C-peptide generated in response to eating a meal.

    Copyrighted material provided for educational purposes only.

    Journal article: https://gut.bmj.com/content/gutjnl/early/2020/10/25/gutjnl-2020-322630.full.pdf
    Personal note: this article is very well written, and easy to read. The authors often describe why they chose to do one thing rather than another, so it is very informative. People who want to understand why the gut microbiota might effect T1D can read the introduction for a quick, easy to understand justification.

    Clinical trial registry: https://www.trialregister.nl/trial/3542


    Remembering that C-peptide is a measure of the body's ability to generate insulin, people who got the "transplant from self" treatment in their honeymoon phase did not deteriorate (in terms of generated C-peptide) over the next year. Those who got the "transplant from healthy" treatment lost their ability to generate insulin (as would be expected over the course of the honeymoon).

    But, what does this mean? Is it important? Will it lead to a cure? These are the open questions. When I started this blog, results like this made me optimistic. I thought that if a treatment could preserve beta cells in early testing, then as we learned more about it, later tests might show it increased beta cells and lead to a cure. However, that has not happened in any of the treatments which showed this result early on. Therefore, I'm no longer so positive about them.

    My current thinking is that these results are more likely to grow into a delay or prevention rather than a cure. In particular, if this treatment had the same effect on people who were at-risk of T1D, as this study showed for people in the honeymoon phase, then it would naturally cause a delay. If prevention turns out to be the natural result of a long delay, then this treatment could become that as well. All that would be required is to see the same results seen here, but in at-risk people rather than honeymooners. Of course, we can still hope for it turning in a cure, but that is less likely.

    One interesting point about this result, is that the good effect was seen in the "transplant from self" group, rather than the "transplant from healthy" group. It seems more likely that a transplantation from someone who did not have T1D would be beneficial while moving Microbiota around within the same person would not change anything. However, in fact, the reverse is seen. That is an odd result (at least to me) so I'm interested in seeing where it goes, if it goes anywhere.

    The researchers wanted to include 34 people in their study (17 in each group). Unfortunately, they were not funded enough to do that, so they ended up with 20 people (10 in each group). Luckily, their results were strong enough to show up with the smaller numbers, but that is not often true. So this study shows the practical impact of less money for research: fewer subjects in each study, and more uncertainty in the outcomes because of that.

    Other Research

    Only one other clinical trial is testing FMT right now. It is a pilot study, enrolling 10 people:

    There are several clinical trials using probiotics to try to improve a patient's T1D. This can be viewed as an alternate treatment to FMT, both of which are based on the same "gut based T1D" theory.

    Joshua Levy
    publicjoshualevy at gmail dot com
    All the views expressed here are those of Joshua Levy, and nothing here is official JDRF or JDCA news, views, policies or opinions. My daughter has type-1 diabetes and participates in clinical trials, which might be discussed here. My blog contains a more complete non-conflict of interest statement. Thanks to everyone who helps with the blog.

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