FMT:Delivery Systems and Methodologies Alexander Khoruts, MD University of Minnesota 2014 James W. Freston Single Topic Conference

Disclosures Research Funding CIPAC Limited: Research Grant Support for Preparation of Standardized Fecal Microbiota NIH University of Minnesota

Current Delivery Methods Enema Nasogastric Tube Nasoduodenal Tube Flexible sigmoidoscopy Colonoscopy Upper endoscopy

Dr. Ben Eiseman (1917 - 2012) “In the early days of oral antibiotics we were plagued by frequent diarrhea in our patients due presumably to killing off intestinal bacteria. I was Chief of Surgery at the VA and simplistically considered merely reintroducing normal organisms to counter such absence. Those were days when if one had an idea, we simply tried it. It seemed to work and I wrote it up. It made a small splash…Best wishes. Ben Eiseman, Emeritus Professor of Surgery — Now age 93.” (Sept. 20, 2011)

Enema Sample Protocol: Retention enema (may use a rectal balloon). Start in the left lateral decubitus position. Administer 60 mL q15 minutes x 4. Infuse slowly over 5 minutes, and ask the patient to rotate slowly over 10 minutes to right lateral decubitus position. Repeat. No need for sedation No need for endoscopist Poor anal sphincter tone may be problematic No diagnostic information regarding possible underlying bowel disease Uncertain delivery of material quantity Multiple administrations may be required Nursing personnel, room, facility fees, lack of reimbursement

Nasogastric/Nasoduodenal Infusion 500 mL of fecal suspension administered via nasoduodenal tube at a rate of 50 mL/2-3 minutes

Nasogastric/Nasoduodenal Infusion Radiologic procedure/fees associated with nasoduodenal tube placement Vomiting and aspiration is a potential risk associated with NG administration. Consider excluding patients with gastroparesis, large hiatal hernia, reflux disease Small bowel response to large quantities of fecal microbiota are unknown, but the procedure generally appears to be well-tolerated Viability of donor microbiota following exposure to stomach acid and the digestive small bowel environment is unknown

Endoscopic Administration: Colonoscopy, Flexible Sigmoidoscopy, (Upper Endoscopy) Relatively simple within the US infrastructure with available endoscopic expertise Diagnostic information regarding underlying disease Certainty of delivery

Preparation Antibiotics regiment Purging of the GI tract prior to the procedure

Fecal Microbiota Transplant Katie Scott, New York Times, 2013

Beginnings…

UMN Microbiota Therapeutics Program Donor Recruitment Donor Screening Donor Laboratory Testing Donation Manufacturing Laboratory/ Manufacturing Cryopreservation Release

UMN Microbiota Therapeutics Program Rigorous Donor Screening and Testing GMP Manufacturing Antibiotic usage within 6 months Infectious disease testing monthly (enteric and blood-borne) Metabolic Syndrome Autoimmunity Allergic/atopic disease Malnutrition Neurologic and neurodevelopmental disorders Clean, inspected facility Consistent Manufacturing Protocol Standardized Dosing (number of bacteria, etc.) Cryopreservation Tracking each unit Malnutrition Release criteria based on donor testing and manufacturing standards

Full-Spectrum MicrobiotaTM versus Defined Microbiota Petrof, E. and Khoruts, A. Gastroenterology 2014

Recipient Microbiota R-CDI IBD IBS NASH Autism Diabetes

UMN Microbiota Therapeutics Program Michael J. Sadowsky Matthew Hamilton Alexa Weingarden JT Kang Aleh Bobr Carolyn Graiziger Amanda Kabage