Skip to content
  • About
  • Contact
  • Contribute
  • Book
  • Careers
  • Podcast
  • Recommended
  • Speaking
  • All
  • Physician
  • Practice
  • Policy
  • Finance
  • Conditions
  • .edu
  • Patient
  • Meds
  • Tech
  • Social
  • Video
    • All
    • Physician
    • Practice
    • Policy
    • Finance
    • Conditions
    • .edu
    • Patient
    • Meds
    • Tech
    • Social
    • Video
    • About
    • Contact
    • Contribute
    • Book
    • Careers
    • Podcast
    • Recommended
    • Speaking

4 reasons why fecal transplants aren’t mainstream. Yet.

Alexander Khoruts, MD
Conditions
February 23, 2015
Share
Tweet
Share

Fecal microbiota transplantation (FMT) has emerged as an increasingly common treatment for patients with refractory Clostridium difficile infection (CDI). Unlike standard antibiotic approaches, which only exacerbate dysbiosis and may perpetuate CDI recurrence, FMT restores normal gut microbial community structure and function of the gastrointestinal tract. However, a number of challenges need to be overcome before this procedure is widely accepted in mainstream clinical practice.

Before I jump into highlighting the number of practical barriers that are associated with FMT, I want to make clear that none of these issues represent insurmountable hurdles. The development of an efficient, safe and reliable transplant mechanism is certainly within technological reach.

Roadblock #1: Donor selection

Historically, an ideal FMT donor was considered a close family member, an intimate partner or a trusted friend; and patients were tasked with identifying their donor. However, there is no evidence that relatedness of a donor impacts the patient’s clinical outcome. Further, it is appropriate to consider the general health of the donor, which may be overlooked by a patient desperate to receive FMT.

The donor problem can be solved by the development of a dedicated, standardized donor program. In this ideal system, stool donors will be screened in a similar fashion to blood donors, with additional consideration of systemic problems, such as metabolic syndrome, diabetes, autoimmunity, inflammatory bowel disease, colon cancer risk,  irritable bowel syndrome, food intolerances, allergies, and neurologic and psychiatric problems. Further, potential donors cannot have a history of recent antibiotic exposure. While this would limit the number of eligible donors dramatically, the program is feasible because qualified donors can provide repeated donations, supplying sufficient material for an extensive FMT program. (While on this topic: you may have recently read that the nonprofit OpenBiome has created a stool bank for FMT, enticing healthy donors with up to $13,000 a year for their stool donations.)

Roadblock #2: Material processing

While FMT can be performed using whole stool, such a procedure can be very challenging esthetically. However, it is possible to separate the microbial portion from fecal material, and even more importantly, it is possible to freeze this microbial fraction while maintaining the viability of the different microbial taxa and clinical efficacy of the preparation.

There are several important advantages in using the frozen microbial fraction instead of the freshly prepared stool. First, the material is no longer esthetically challenging, having lost most of the potent pungent odor associated with stool. Second, the preparation can be quantified in terms of numbers and types of bacteria present rather than the crude measure of stool weight, which can vary in bacterial content between individual donations. Most importantly, the ability to bank the microbiota material before its use allows performance of rigorous testing and elimination of uncertainty associated with freshly prepared material.

Roadblock #3: Standardization

While there is currently no set standardization process in place, the entire process of producing fecal microbiota material can be standardized in accordance with the Current Good Manufacturing Practices (CGMPs), which is used and enforced by FDA to ensure proper design, monitoring and control of the manufacturing processes and facilities. Adherence to CGMPs is absolutely critical to large-scale manufacture of fecal microbiota preparation that may enter routine clinical practice. The ultimate purpose in the manufacture of a product as complex as fecal microbiota is not to obtain precise compositional consistency, which is impossible given that composition of every donation is somewhat different and gut microbiota is intrinsically dynamic. However, CGMPs do ensure that the manufacturing process is consistent between different batches, and any possibility of introducing risk is minimized.

Roadblock #4: Regulations on biotechs

The spectacular success of FMT in treating refractory CDI has provided a boost to various biotechnology start-up manufacturing companies that are attempting to harness the power of the microbiome for novel therapeutics development. Different companies are taking varying approaches to develop fecal microbiota–based products, including standardized whole donor-derived microbiota; highly simplified, defined microbial consortia; and hybrid products, such as SER-109, the lead spore-based compound from Seres Health (Cambridge, MA), which recently was reported to have promising early results in recurrent CDI. The pace of discovery and clinical validation is accelerating, and it appears very likely that a range of highly effective therapeutic options for CDI and perhaps other indications, soon will be introduced into mainstream medicine.

However, in addition to the many scientific and technical hurdles, developers also are challenged by the fluid regulatory framework and uncertainties in the intellectual property landscape. While FDA issued a policy of “enforcement discretion” for physicians using FMT on patients with refractory CDI not responding to standard therapies, these restrictions have been applied unevenly to commercial entities.

Functionally, gut microbiota fit the description of an organ and given its tight co-evolutionary linkage to its specific host species, it can be considered a human organ composed of microbial cells. Therefore, it may be more reasonable for FDA to borrow elements of regulation for microbiota products from those applied to tissue transplantation, rather than those applied to new drugs.

Moving forward

ADVERTISEMENT

Most importantly, therapeutic development in this area should be guided by the best science. We have the medical community on our side, as the American Gastroenterological Association has developed the AGA Center for Gut Microbiome Research and Education to continue to advance research on the gut microbiome in human health and disease.

Ultimately, we all — physicians, scientists, developers and regulators — need to be informed by continued research, basic and clinical, to allow establishment of this promising new class of therapeutics into mainstream medicine.

Alexander Khoruts is a gastroenterologist.

Prev

Which drugs are on formulary? A little help, please.

February 23, 2015 Kevin 5
…
Next

Lessons from my first nasogastric tube

February 23, 2015 Kevin 7
…

Tagged as: Gastroenterology

Post navigation

< Previous Post
Which drugs are on formulary? A little help, please.
Next Post >
Lessons from my first nasogastric tube

ADVERTISEMENT

More by Alexander Khoruts, MD

  • A clinician’s guide to microbiome testing

    Alexander Khoruts, MD

More in Conditions

  • How President Biden’s cognitive health shapes political and legal trust

    Muhamad Aly Rifai, MD
  • The emotional first responders of aesthetic medicine

    Sarah White, APRN
  • Why testosterone matters more than you think in women’s health

    Andrea Caamano, MD
  • How veteran health care is being transformed by tech and teamwork

    Deborah Lafer Scher
  • What Elon Musk and Diddy reveal about the price of power

    Osmund Agbo, MD
  • Understanding depression beyond biology: the power of therapy and meaning

    Maire Daugharty, MD
  • Most Popular

  • Past Week

    • The hidden health risks in the One Big Beautiful Bill Act

      Trevor Lyford, MPH | Policy
    • How New Mexico became a malpractice lawsuit hotspot

      Patrick Hudson, MD | Physician
    • Why doctors are reclaiming control from burnout culture

      Maureen Gibbons, MD | Physician
    • Why health care leaders fail at execution—and how to fix it

      Dave Cummings, RN | Policy
    • How digital tools are reshaping the doctor-patient relationship

      Vineet Vishwanath | Tech
    • How President Biden’s cognitive health shapes political and legal trust

      Muhamad Aly Rifai, MD | Conditions
  • Past 6 Months

    • Why tracking cognitive load could save doctors and patients

      Hiba Fatima Hamid | Education
    • Why are medical students turning away from primary care? [PODCAST]

      The Podcast by KevinMD | Podcast
    • What the world must learn from the life and death of Hind Rajab

      Saba Qaiser, RN | Conditions
    • Why “do no harm” might be harming modern medicine

      Sabooh S. Mubbashar, MD | Physician
    • Here’s what providers really need in a modern EHR

      Laura Kohlhagen, MD, MBA | Tech
    • The hidden health risks in the One Big Beautiful Bill Act

      Trevor Lyford, MPH | Policy
  • Recent Posts

    • How President Biden’s cognitive health shapes political and legal trust

      Muhamad Aly Rifai, MD | Conditions
    • Decoding your medical bill: What those charges really mean

      Cheryl Spang | Finance
    • The emotional first responders of aesthetic medicine

      Sarah White, APRN | Conditions
    • Why testosterone matters more than you think in women’s health

      Andrea Caamano, MD | Conditions
    • A mind to guide the machine: Why physicians must help shape artificial intelligence in medicine

      Shanice Spence-Miller, MD | Tech
    • How subjective likability practices undermine Canada’s health workforce recruitment and retention

      Olumuyiwa Bamgbade, MD | Physician

Subscribe to KevinMD and never miss a story!

Get free updates delivered free to your inbox.


Find jobs at
Careers by KevinMD.com

Search thousands of physician, PA, NP, and CRNA jobs now.

Learn more

View 1 Comments >

Founded in 2004 by Kevin Pho, MD, KevinMD.com is the web’s leading platform where physicians, advanced practitioners, nurses, medical students, and patients share their insight and tell their stories.

Social

  • Like on Facebook
  • Follow on Twitter
  • Connect on Linkedin
  • Subscribe on Youtube
  • Instagram

ADVERTISEMENT

  • Most Popular

  • Past Week

    • The hidden health risks in the One Big Beautiful Bill Act

      Trevor Lyford, MPH | Policy
    • How New Mexico became a malpractice lawsuit hotspot

      Patrick Hudson, MD | Physician
    • Why doctors are reclaiming control from burnout culture

      Maureen Gibbons, MD | Physician
    • Why health care leaders fail at execution—and how to fix it

      Dave Cummings, RN | Policy
    • How digital tools are reshaping the doctor-patient relationship

      Vineet Vishwanath | Tech
    • How President Biden’s cognitive health shapes political and legal trust

      Muhamad Aly Rifai, MD | Conditions
  • Past 6 Months

    • Why tracking cognitive load could save doctors and patients

      Hiba Fatima Hamid | Education
    • Why are medical students turning away from primary care? [PODCAST]

      The Podcast by KevinMD | Podcast
    • What the world must learn from the life and death of Hind Rajab

      Saba Qaiser, RN | Conditions
    • Why “do no harm” might be harming modern medicine

      Sabooh S. Mubbashar, MD | Physician
    • Here’s what providers really need in a modern EHR

      Laura Kohlhagen, MD, MBA | Tech
    • The hidden health risks in the One Big Beautiful Bill Act

      Trevor Lyford, MPH | Policy
  • Recent Posts

    • How President Biden’s cognitive health shapes political and legal trust

      Muhamad Aly Rifai, MD | Conditions
    • Decoding your medical bill: What those charges really mean

      Cheryl Spang | Finance
    • The emotional first responders of aesthetic medicine

      Sarah White, APRN | Conditions
    • Why testosterone matters more than you think in women’s health

      Andrea Caamano, MD | Conditions
    • A mind to guide the machine: Why physicians must help shape artificial intelligence in medicine

      Shanice Spence-Miller, MD | Tech
    • How subjective likability practices undermine Canada’s health workforce recruitment and retention

      Olumuyiwa Bamgbade, MD | Physician

MedPage Today Professional

An Everyday Health Property Medpage Today
  • Terms of Use | Disclaimer
  • Privacy Policy
  • DMCA Policy
All Content © KevinMD, LLC
Site by Outthink Group

4 reasons why fecal transplants aren’t mainstream. Yet.
1 comments

Comments are moderated before they are published. Please read the comment policy.

Loading Comments...