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 Dysbiosis – reduced diversity of organisms that reduce intestinal health Healthy flora – broad diversity of organisms that provide intestinal health

Dysbiosis –Antibiotics, Unhealthy Diet, Flora-Associated Disorder or Intestinal Infection 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) 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 1 st time in a year I can hold a grandchild” FMT # 1-69 Chairman, Department Head, sent the university his resignation, cured by FMT, rescinded his resignation, “you saved my life” Our Patients Remind of Us of the Miracle of FMT 20-yr old lost 40 lbs (down to 88 lbs), was cured by FMT and organized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 and after 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 Intestinal Flora Dysbiosis Targets 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 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 most 1 Study 70 patients in placebo- controlled trial FMT/placebo enemas weekly for six weeks,with significant improvement in remission 2 1 Colman RG et al. J Crohn’s & Colitis 2014;8: (meta-analysis) 2 Moayyedi P et al Gastroenterology 2015;149:

Conclusions and Summary Intestinal flora 2 nd 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!