What is the Deal About What is the Deal About FMT?FMT?

Herbert L. DuPont, MDDirector, 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 Unhealthy vs. Healthy Intestinal FloraIntestinal Flora

Dysbiosis – reduced diversity of organisms that reduce intestinal health

Healthy flora – broad diversity of organisms that provide intestinal health

Dysbiosis –Antibiotics, Unhealthy Diet, Dysbiosis –Antibiotics, Unhealthy Diet, Flora-Associated Disorder or Intestinal Flora-Associated Disorder or Intestinal

InfectionInfection

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 - For Depletion of Diversity of Microflora - Fecal Microbiota Transplantation (FMT)Fecal Microbiota Transplantation (FMT)

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

FMT # 1-9“Thank you!, Thank you!, Thank you!

For the 1st time in a year I can holda grandchild”

FMT # 1-69Chairman, Department Head, sentthe university his resignation, cured by FMT,rescinded his resignation, “you saved my life”

Our Patients Remind of Us of the Miracle of Our Patients Remind of Us of the Miracle of FMTFMT

20-yr old lost 40 lbs (down to 88 lbs), was cured by FMT and organized fund raising

event to pay for medical expenses

FMT 2 #10

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

FMT 1 #69

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

Fecal Microbiota in Recipients Before andafter Fecal Microbiota Transplantation

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 Partial List of Conditions With Intestinal Flora DysbiosisIntestinal Flora Dysbiosis

Targets for FMT TrialsTargets for FMT Trials

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 IBDFMT for Management of IBD

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 placebo-controlled 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 SummaryConclusions and Summary 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 BacteriaThey are the Only Culture

Some Folks Have!