Professional Societies, Advocacy, and
the Gov’t-How do we get along?
Gary D. Wu, M.D
Ferdinand G. Weisbrod Professor of Medicine
Division of Gastroenterology
Perelman School of Medicine
University of Pennsylvania
The AGA Center for Gut
Microbiome Research &
Education
The Center’s Mission Statement
To advance research and education on the
gut microbiome in human health and disease.
The Center will serve as the focus of all AGA activities
and programs in this field and will be built around the
pillars of the AGA Strategic Plan: Research-EducationAdvocacy-Practice.
AGA Microbiome Scientific Advisory Board
Provides guidance to AGA Board on
scientific matters relevant to the
microbiome: strategic direction,
topic and programmatic priorities,
program participants. Eight
members representing:
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Computational biology
Metagenomics
Animal models
Microbiology
Translational research
Nutrition and obesity
Motility
Pediatrics
Clinical Practice (FMT)
Regulatory and policy
issues
Members:
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Gary D. Wu, MD, SAB Chair, University of
Pennsylvania, Philadelphia, PA
Martin J. Blaser, MD, New York University,
New York, NY
Gail A. Hecht, MD, Loyola University,
Maywood, IL
Purna Kashyap, MD, Mayo Clinic,
Rhochester, MN
Colleen Kelly, MD, Brown University,
Providence, RI
Lee M. Kaplan, MD, PhD, Harvard
University/MGH, Boston, MA
Rob Knight, PhD, University of Colorado,
Boulder, CO
Loren Laine, MD, Yale University, New
Haven, CT
Mary Ellen Sanders, PhD, Consultant,
Centennial, CO
R. Balfour Sartor, MD, University of North
Carolina, Chapel Hill, NC
Phillip Tarr, MD, Wash. Univ., St. Louis, MO
Ex officio mbrs: Council chair; GB basic
science councillor
Fecal Microbiota Transplantation (FMT), a Success Story for
the Treatment of Refractory CDI—But with a Note of Caution
Prescreening of donors to
prevent transmission of
currently known pathogens
Homogenization, filtration,
and administration usually
through a colonoscope.
• Success rate of around 90% when fecal microbiota
transplantation (FMT) is used to treat CDI
• Currently over 500 cases reported in the literature
• Placebo-controlled clinical trial: Duodenal Infusion of Donor Feces
for Recurrent Clostridium difficile. N Engl J Med 2013; 368:407-41
Response of the Microbiome Center SAB to Issues
Related to FDA FMT IND for CDI
• May 2013: Notification of AGA membership that an IND was required for
FMT used for any indication including the treatment of refractory CDI.
Emergency use IND hotline provided to membership.
• Nine member committee established (5 AGA, 2 NASPGHAN, 2 IDSA) to
provide feedback to FDA regarding IND for FMT.
• FDA issues “regulatory restraint” on use of FMT for CDI—AGA membership
notified of decision.
• AGA committee develops “Current Consensus Guidance on Donor Screening
and Stool Testing for FMT” document for FDA together with IDSA,
NASPGHAN, ACG, and ASGE.
“You Shouldn’t Do it Just Because You Can—Caution about
FMT and the Need for Regulation
Although the short-term infectious risks of FMT seem to be definable and quantifiable,
we should remember the entire generation of patients infected with HCV by blood
transfusion before this pathogen was identified.
The field should move cautiously because the long-term consequences of FMT in
humans are unknown.
• The gut microbiome contains a highly complex and dense community of microbes
that include bacteria, fungi and viruses, many of which have not been fully
characterized.
• It is a dynamic and living consortium that can change over time in ways that
scientists cannot currently fully predict.
• Animal model data suggests that the gut microbiome may play a role in the
pathogenesis of several human diseases.
Viruses
Predator-Prey
Enhanced
Relationship Pathogenicity
Bacteria
Normon et al.
Gastro 2014
Archaea
Fungi
Publications on FMT for the Clinician
“A How to Guide: Investigational New Drug Application for Fecal Microbiota Transplantation”
Colleen R. Kelly, MD; Sachin S. Kunde, MD, MPH; Alexander Khoruts, MD
Clinical Gastroenterology and Hepatology
What's the Value of an FDA IND for Fecal Microbiota Transplantation in Clostridium difficile
Infection?
Gail A. Hecht, MD, MS and Members of the SAB for the AGA Center for Gut Microbiome
Research and Education
Clinical Gastroenterology and Hepatology
AGA-Sponsored Webinar: In planning stages
The Scientific Value of FMT
FMT and the Treatment of Type 2 Diabetes
•The success of FMT in the treatment of CDI is “proof of principle” that
the dysbiotic human microbiota can be modified to treat disease.
•Emphasizes the importance of using a resilient microbial community
to modify dysbiosis.
•FMT is a window into the biology of the gut microbiome in humans:
• Translation of findings in animal models into human biology.
• Understand the long term consequences of manipulating the gut microbiota in humans
The Future of FMT: Transplantation of Defined
Microbial Communities
•Customization of consortium membership of bacteria with
specific biological properties to produce predictable responses
and reduce both short- and long-term adverse outcomes
•Laboratory defined conditions prevent pathogen transmission
•Development of standardized conditions for the transplantation
(inoculation) and maintenance of the community
•Durable communities that are resilient to change
Evolution of Microbiome Research
Animal Models
(functional data)
Human Association
Studies
FMT for CDI
Novel Therapeutics
Next generation pre-, pro-,
synbiotics
Evolution of the microbiome field
Human Intervention
Studies
Past/Current
Status of the
field: “Safe”
traditional view.
Future status of the
field: Higher risk but
higher reward.
The Progression of Science, Reduction to Practice, and
Development of New Gut Microbiota-Based Products
Evolution of Scientific
and Product
Development
CDI
FMT
Processed Fecal
Products
Yes
Likely Yes
Defined Microbial
Consortia
Possibly Yes
Lawley TD PLoS Pathog. 2012;8(10):e1002995
Petrof EO. Microbiome. 2013 Jan 9;1(1):3
Other diseases
Safety
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Initiation
Focus of
technology
development
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Sustainability
Goals of the FMT Registry
• To gather information on practice in the U.S. and assess effectiveness of the intervention.
• To assess short-term and long-term safety.
• To aid practitioners and sponsors in satisfying regulatory requirements.
• To promote scientific investigation.
A National FMT Registry
•AGA Microbiome Center Scientific Advisory Board
•Infectious Disease Society of America (IDSA)
•NASPGHAN
•CCFA
AGA
Registry expertise
with a CRO (ACI
Clinical)
Penn-CHOP
Microbiome
Initiative
FMT Registry
Biobank
NIH NIAID Application for a
R24 (resource related
research project)
Stool/microbial products
FDA
Professional Societies
Oversight of FMT, Stool-based
products, and “next generation”
probiotics
Clinical practice standards
(efficacy/safety), liability,
reimbursement
Academia, CDC, NIH and
Other (i.e. Industry)
Basic and clinical investigation,
product development
Thank You