Transcript What is the deal with Fecal Microbiota Transplant (FMT)

What is the Deal About
FMT?
Herbert L. DuPont, MD
Director, Center for Infectious Diseases, University of Texas
School of Public Health
President, Kelsey Research Foundation
Mary W. Kelsey Distinguished Chair in Medical Sciences,
University of Texas Medical School, Houston
Clinical Professor Infectious Diseases and Microbiology,
Baylor College of Medicine
Unhealthy vs. Healthy
Intestinal Flora
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Dysbiosis – reduced
diversity of organisms
that reduce intestinal
health
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Healthy flora – broad
diversity of organisms
that provide intestinal
health
Dysbiosis –Antibiotics, Unhealthy Diet,
Flora-Associated Disorder or Intestinal
Infection
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Normal diverse intestinal flora:
“Richness & Evenness”
Antibiotics ablate diversity and
allow flora blooms
encouraging horizontal
movement of genes and
pathogens
Pure dysbiosis: Clostridium
difficile infection
For Depletion of Diversity of Microflora Fecal Microbiota Transplantation (FMT)
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Donor selection and screening
process
≥ 50 g of stool is collected and
mixed in stomacher and filtered
twice to remove fecal material
Study 1: fresh, frozen or lyophilized
(freeze-dried) bacterial product
dispensed via colonoscope
Study 2: frozen product given by
enema and lyophilized by oral
capsule
Our Patients Remind of Us of the
Miracle of FMT
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We have treated
more than >90
patients with
recurrent C diff
infection by FMT
 Success rate
90%; failures
receive second
FMT from a
different donor
 Our patients will
show you how
grateful they are
FMT # 1-9
“Thank you!, Thank you!, Thank you!
For the 1st time in a year I can hold
a grandchild”
FMT
2 #10
FMT # 1-69
Chairman, Department Head, sent
the university his resignation, cured by FMT,
rescinded his resignation, “you saved my life”
FMT
1 #69
20-yr old lost 40 lbs (down to 88 lbs), was
cured by FMT and organized fund raising
event to pay for medical expenses
19-yr old college football player with ulcerative colitis
and 4 episodes of C diff infection with 90 lbs of weight
loss was cured by FMT and he is back playing football
Fecal Microbiota in Recipients Before and
after Fecal Microbiota Transplantation
Relative Abundance (%)
80
60
Fusobacteria
Actinobacteria
Proteobacteria
Verrucomicrobia
Bacteroidetes
Firmicutes
40
20
0
BeforeFMT
7dpFMT
14dpFMT
30dpFMT
Recipients After ≥ 3 Bouts of CDI
Fecal Flora Diversity in 8 Donors and 41 Recipients
Before and After Fecal Microbiota Transplantation
Recipients After ≥ 3 Bouts of CDI
Partial List of Conditions With
Intestinal Flora Dysbiosis
Targets for FMT Trials
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Inflammatory bowel disease
Irritable bowel syndrome
Type II diabetes and metabolic
syndrome
Non-alcoholic fatty liver disease
Rheumatoid arthritis
Chronic neurologic diseases (e.g.
MS, Parkinson’s disease)
Allergic disorders and asthma
Allogeneic hematopoietic stem cell
transplantation*
Obesity
*resulting in bacteremia and C. difficile infection
FMT for Management of IBD
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Dysbiosis commonly found in
patients: ↓ in Firmicutes and ↑ in
Proteobacter (resembling CDI)
18 studies have looked at efficacy
of FMT; most single treatment;
with mixed results although flora
improved in most1
Study 70 patients in placebocontrolled trial FMT/placebo
enemas weekly for six weeks,with
significant improvement in
remission2
1 Colman RG et al. J Crohn’s & Colitis 2014;8:1569-81 (meta-analysis)
2 Moayyedi P et al Gastroenterology 2015;149:102-109
Conclusions and Summary
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Intestinal flora 2nd body Genome
influencing health by its diversity
FMT is a powerful low-tech physiologic
means of reversing dysbiosis that is being
harnessed to treat non GI diseases
We are now applying for IND to move into
several other conditions associated with
dysbiosis using enemas and capsules
The medium long-range future of FMT –
not great!
We will be moving into modern generation
probiotics that help control diversity of
flora in patients with dysbiosis – This will
move the field dramatically forward
Support Bacteria
They are the Only Culture
Some Folks Have!