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
46 Shares
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

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

More by Alexander Khoruts, MD

  • A clinician’s guide to microbiome testing

    Alexander Khoruts, MD

More in Conditions

  • Overcoming Parkinson’s: a journey of laughter and resilience

    Cynthia Poire Mathews, FNP
  • The untold struggles patients face with resident doctors

    Denise Reich
  • Maximize sleep efficiency with stimulus control

    Pedram Navab, DO
  • The endless waves of chronic illness

    Michele Luckenbaugh
  • Surviving and thriving after life’s most difficult moments

    Rebecca Fogg, MBA
  • The surprising power of Play-Doh in pediatric care: How it’s bringing families together

    Alexander Rakowsky, MD
  • Most Popular

  • Past Week

    • The real cause of America’s opioid crisis: Doctors are not to blame

      Richard A. Lawhern, PhD | Meds
    • It’s time for C-suite to contract directly with physicians for part-time work

      Aaron Morgenstein, MD & Corinne Sundar Rao, MD | Physician
    • What is driving physicians to the edge of despair?

      Edward T. Creagan, MD | Physician
    • The untold struggles patients face with resident doctors

      Denise Reich | Conditions
    • The psychoanalytic hammer: lessons in listening and patient-centered care

      Greg Smith, MD | Conditions
    • 10 commandments of ethical affiliate marketing for physicians

      Aaron Morgenstein, MD & Amy Bissada, DO | Finance
  • Past 6 Months

    • The real cause of America’s opioid crisis: Doctors are not to blame

      Richard A. Lawhern, PhD | Meds
    • Nobody wants this job. Should physicians stick around?

      Katie Klingberg, MD | Physician
    • The vital importance of climate change education in medical schools

      Helen Kim, MD | Policy
    • The fight for reproductive health: Why medication abortion matters

      Catherine Hennessey, MD | Physician
    • It’s time for C-suite to contract directly with physicians for part-time work

      Aaron Morgenstein, MD & Corinne Sundar Rao, MD | Physician
    • Resetting the doctor-patient relationship: Navigating the challenges of modern primary care

      Jeffrey H. Millstein, MD | Physician
  • Recent Posts

    • 10 commandments of ethical affiliate marketing for physicians

      Aaron Morgenstein, MD & Amy Bissada, DO | Finance
    • The heart of a Desi doctor: Balancing emotions and resources in oncology

      Dr. Damane Zehra | Physician
    • Safe sex for seniors: Dispelling myths and embracing safe practices [PODCAST]

      The Podcast by KevinMD | Podcast
    • Overcoming Parkinson’s: a journey of laughter and resilience

      Cynthia Poire Mathews, FNP | Conditions
    • The untold struggles patients face with resident doctors

      Denise Reich | Conditions
    • Maximize sleep efficiency with stimulus control

      Pedram Navab, DO | Conditions

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

CME Spotlights

From MedPage Today

Latest News

  • Four-Year-Old Gets Hospital Bill; Woolly Mammoth Meatball; How AR-15s Damage Humans
  • How This Doctor Found Purpose After a Devastating Injury
  • House Lawmakers Squabble Over HHS Budget
  • Infant Formula Crisis Exposed FDA and Industry Failings, Lawmakers Say
  • Building Vaccine Trust Among the General Public

Meeting Coverage

  • Phase III Trials 'Hit a Home Run' in Advanced Endometrial Cancer
  • Cannabis Use Common in Post-Surgery Patients on Opioid Tapering
  • Less Abuse With Extended-Release Oxycodone, Poison Center Data Suggest
  • Novel Strategies Show Winning Potential in Ovarian Cancer
  • Children Do Well With Fewer Opiates After Surgery
  • Most Popular

  • Past Week

    • The real cause of America’s opioid crisis: Doctors are not to blame

      Richard A. Lawhern, PhD | Meds
    • It’s time for C-suite to contract directly with physicians for part-time work

      Aaron Morgenstein, MD & Corinne Sundar Rao, MD | Physician
    • What is driving physicians to the edge of despair?

      Edward T. Creagan, MD | Physician
    • The untold struggles patients face with resident doctors

      Denise Reich | Conditions
    • The psychoanalytic hammer: lessons in listening and patient-centered care

      Greg Smith, MD | Conditions
    • 10 commandments of ethical affiliate marketing for physicians

      Aaron Morgenstein, MD & Amy Bissada, DO | Finance
  • Past 6 Months

    • The real cause of America’s opioid crisis: Doctors are not to blame

      Richard A. Lawhern, PhD | Meds
    • Nobody wants this job. Should physicians stick around?

      Katie Klingberg, MD | Physician
    • The vital importance of climate change education in medical schools

      Helen Kim, MD | Policy
    • The fight for reproductive health: Why medication abortion matters

      Catherine Hennessey, MD | Physician
    • It’s time for C-suite to contract directly with physicians for part-time work

      Aaron Morgenstein, MD & Corinne Sundar Rao, MD | Physician
    • Resetting the doctor-patient relationship: Navigating the challenges of modern primary care

      Jeffrey H. Millstein, MD | Physician
  • Recent Posts

    • 10 commandments of ethical affiliate marketing for physicians

      Aaron Morgenstein, MD & Amy Bissada, DO | Finance
    • The heart of a Desi doctor: Balancing emotions and resources in oncology

      Dr. Damane Zehra | Physician
    • Safe sex for seniors: Dispelling myths and embracing safe practices [PODCAST]

      The Podcast by KevinMD | Podcast
    • Overcoming Parkinson’s: a journey of laughter and resilience

      Cynthia Poire Mathews, FNP | Conditions
    • The untold struggles patients face with resident doctors

      Denise Reich | Conditions
    • Maximize sleep efficiency with stimulus control

      Pedram Navab, DO | Conditions

MedPage Today Professional

An Everyday Health Property Medpage Today iMedicalApps
  • 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...