Ask the Researchers: Part 1

October 22, 2020
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Dr. Alexander Khoruts, Medical Director of the University of Minnesota Microbiota Therapeutics Program

You asked... the researchers answered! Read on for the first installment of our two part series with some of the leading researchers in microbiota therapy. Our first Q&A session is with Dr. Alexander Khoruts, Medical Director of the University of Minnesota Microbiota Therapeutics Program. Interested in learning more? Check out our virtual event, Spread Hope to hear more from Dr. Khoruts and other experts. Have a question you'd like featured on our blog? Ask here!

Q.       How do children (4-5 years) receive IMT capsules?

A.      Currently, we have only minimal experience with using IMT capsules in such young patients. We did successfully treat a 5 year-old with autism. This patient had no problems swallowing pills. However, we realize this is a challenge and development of a pediatric-friendly oral formulation is one of the emerging projects.

Q.     Can IMT capsules be prescribed?

A.     No. This is an investigational preparation and it is not available for prescription at this time. It is likely that commercial preparations based in part on our work will emerge in the coming years. However, it is important to realize that this is an entirely new class of therapeutics and physicians will also require a lot of education on how to use them. One cannot simply extrapolate from C. difficile experience to other indications, even though the legal framework in our country assumes that physicians will know that. I worry that they won't.

Q.       What safety measures are taking now that we are in this unprecedented time with Covid-19?  Has Covid-19 impacted your ability to procure donors? If so, to what extent?

A.      We were shut down for a number of months by the University, as was all non-COVID research. In addition, we had to develop a protocol to monitor and frequently test our donors. This protocol was approved by the FDA. We are fully operational now.

Q.       What are the implications post transplant for a diverse diet? What are the typical steps post transplant for life long benefits?

A.      This is an excellent question that has not yet been addressed experimentally. We think that a diet diverse in sources of fiber is the best diet. This is because microbial diversity in the intestine generally correlates with stability and resilience of the intestinal microbial community as well as health of the host. A diverse diet likely helps to foster a diverse microbial community. However, we did not yet have a chance to test this idea in a post-transplant setting.

Q.       Do oral FMT capsules work just as well as FMT delivered via colonoscopy or endoscopy?

A.      Both are quite good in treating C. difficile infections. However, colonoscopic delivery is somewhat more effective (90% versus 80% for capsules). However, the simplicity of the capsule treatment generally makes it preferable to colonoscopy, at least as a first attempt. When it comes to indications other than C. difficile infections, multiple treatments are required. In those cases colonoscopic administration is simply impractical.

Q.       Can oral FMT help with SIBO?

A.      There is no data on that, and there is little reason that it would. However, 'true' SIBO is a very unusual condition, typically seen in patients with major motility disorders like scleroderma, surgical complications (e.g., loss of the ileocecal valve), or partial bowel obstructions. Most patients who are diagnosed with 'SIBO' don't have any of those things; rather it is a possible contributor to irritable bowel syndrome (IBS). Here, the data is all over the place. There are some studies with FMT that show no change, some show benefit, and some show worsening of symptoms. This is clearly an area where answers will require intensive and rigorous research.

Q.       In Dr. Jim Adam‘s Autism study, were selected microbe strains used in FMT?

A.      No. However, patients with autism do have some characteristic differences in their microbiome. Therefore, we rank the donors to compensate for certain microbial groups that were missing in the patients. Thus, we do choose the donors for autism studies based on their microbiome testing in addition to requiring that all other health criteria are satisfied.

Q.       To get best results, should the stool donors be similar to the patients in terms of gender, ethnicity, region they live in or does that not matter?

A.       No evidence for that has yet emerged. Clinical outcomes are not dependent on matching ethnicity or sex, at least in treatment of C. diffiicle infections. In population studies of healthy people virtually no genetic constraints have been identified on the composition of intestinal microbial communities. One exception is lactose intolerance -- people who do not consume milk products because of a genetic problem in digesting lactose do have very minor differences. This is expected as dietary restrictions over long periods of time can lead to extinction of certain microbes that benefit from a particular nutrient. For the most part the core features of intestinal microbial communities are the same in all healthy people. There are fine distinctions between individuals and it is possible to distinguish individuals by their microbiome alone. These differences are not clinically significant in treatment of C. difficile infection. However, when it comes to other indications, e.g., autism or ulcerative colitis, we do think that there are certain functionalities that will prove to be important and careful selection among donors will be required. However, ethnicity or sex are not likely to inform that selection.