Fecal Microbiota Transplantation (FMT)

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Fecal Microbiota Transplantation (FMT)

• Spencer A. Wilson, MD
• Northside Gastroenterology
• September 14, 2013

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Overview

• Intestinal microbiome and host physiology
• Dysbiosis of the microbiome and C. difficile
  infection (CDI)
• Standard Rx of CDI
• FMT for restitution of colonization resistance
• Rx of recurrent/refractory CDI
• The future of FMT

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Intestinal Microbiota

• Includes bacteria, archea (single-celled
  prokaryotes), viruses, fungi and parasites
• gt 50 bacterial phyla described
• Majority anaerobic
• Constitute 60 of dry weight of feces
• Bacteroides, Firmicutes, Actinobacteria,
  Proteobacteria
• 1014 bacterial cells ? 10 times greater than
  number of human cells in our body

Eckburg, PB et al. Science 20053081635-8
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Intestinal MicrobiotaRole in Health and Disease
De Vos, WM. SelfCare 20123(S1)1-68
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Intestinal MicrobiotaAlterations During Human
Life Cycle
Ottman, N. Front Cell Infect Microbiol. 20122104
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Intestinal MicrobiotaEnvironmental Influence
and Immune Response
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Microbiota and Host Physiology
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C. difficile Infection (CDI)

• 1996 2009 in U.S., rates of CDI doubled
• 3 million cases per year
• Unadjusted fatality rate
• 1.2 (2000) ? 2.3 (2004)
• Majority gt 65 y/o
• 3.2 billion dollars excess cost of care

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C. difficile Manifestations

• Carrier state
• C. difficile - associated diarrhea (CDAD)
• C. difficile colitis
• Pseudomembranous colitis
• Fulminant Colitis / Toxic megacolon
• Atypical (e.g., sepsis, ascites)
• Recurrent disease

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Recurrent CDI

• 15-20 of patients
• Relapse
• Re-infection
• Post-CDI irritable bowel syndrome
• 2nd recurrence 40 3rd recurrence 60
• Rx failure before 2003 lt 10 after 2003 20
• Relapses can continue for years
• No universal Rx algorithm

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Why Do We Get Recurrent CDI ?

• Impaired host-response
• Altered intestinal microbiome
• Dysbiosis decreased microbiota diversity

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Host Immune Response to C. difficile Infection

• IgG anti-toxin A protects against diarrhea and
  colitis

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Decreased Diversity of Fecal Microbiome in
Recurrent CDI

• Decreased phylogenic richness in recurrent CDI
• Bacteroidetes reduced in recurrent but not single
  episode CDI
• 
  Chang JY, et al. J
  Infect Dis 2008197435-8

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ACG Rx Guidelines 2013
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Fecal Microbiota Transplantation (FMT)

• Definition Instillation of stool from a healthy
  person into a sick person to cure a certain
  disease
• Rationale A perturbed imbalance in our
  intestinal microbiota (dysbiosis) is associated
  with or causes disease and can be corrected with
  re-introduction of donor feces

Brandt LJ ACG Meeting Oct. 2012
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Recurrent CDI Rationale for FMT

• Avoid prolonged, repeated courses of antibiotics
• Re-establish normal diversity of the intestinal
  microbiome, thus restoring colonization
  resistance

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Early History of FMT

• 4th Century
• Oral human fecal suspension (yellow soup) for
  severe diarrheal illnesses
• 17th Century Veterinary medicine
• Fecal transfer for horses with diarrhea
• 1958 FMT enema
• Eismann, et al. 4 patients with pseudomembranous
  colitis
• Dramatic response within 48 hours

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Protocol for FMT in Recurrent CDI

• Choose donor
• Spouse/partner
• 1st degree relative
• Household contact
• Universal donor
• Donor exclusions
• Antibiotic use within 3 months
• Diarrhea, constipation, IBS, IBD, colorectal CA,
  immunocompromised, anti-neoplastic drugs,
  obesity, metabolic syndrome, atopy, high-risk
  behaviors
• Donor testing
• Stool culture, listeria, OP, C. diff, H.
  pylori Ag, Giardia Ag, cryptosporium Ag,
  acid-fast stain (cyclospora, isospora), Rotavirus
• Blood Hep A, Hep B, Hep C, syphilis, HIV

Brandt LJ ACG Meeting Oct. 2012
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Protocol for FMT in Recurrent CDI

• Recipient
• D/C antibiotics 2-3 days prior to procedure
• Large volume bowel prep evening before FMT
• Loperamide before procedure
• Donor
• Gentle laxative (e.g. MOM) evening before FMT
• Freshly passed stool is used within 6-8 hours
• Stool need not be refrigerated

Brandt LJ ACG Meeting Oct. 2012
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Protocol for FMT in Recurrent CDI

• Stool Transplant
• Donor stool ? suspension with non-bacteriostatic
  saline
• Filtered through gauze into canister
• Use of hood (level 2 biohazard)
• 60 cc catheter tip syringe connected to suction
  tubing
• Volume of 300 mL instilled into ileum and/or
  ascending colon
• Patient to hold stool for 4-6 hours

Brandt LJ ACG Meeting Oct. 2012
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Current History of FMT in Recurrent C.
difficile infection
Kleger, A Schnell, J Essig, A Wagner, M
Bommer, M Seufferlein, T Härter, G Fecal
Transplant in Refractory Clostridium difficile
Colitis Dtsch Arztebl Int 2013 110(7) 108-15
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FMT in Recurrent CDI 1st RCT of FMT vs Oral
Vanco
Van Nood N et. al. NEJM 2013
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FMT in Recurrent CDI 1st RCT of FMT vs Oral
Vanco
Trial stopped early as deemed unethical to
continue
Van Nood N et. al. NEJM 2013
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Follow-up Survey

• 77 patients gt 3 months after FMT
• Duration of illness 11 months
• Symptomatic response after FMT
• lt 3 days in 74
• Primary cure rate 91
• Secondary cure rate 98.7
• 97 of patients would have another FMT for
  recurrent CDI
• 58 would chose FMT as their prefered Rx

Brandt LJ, et al. Am J Gastroenterol 2012
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FMT for Recurrent CDI

• Drawbacks
• Aesthetically unpleasing
• No remibursement
• Cautions
• Potential transmission of pathogens
• Pros
• Re-establishes diversity of intestinal microbiota
• Inexpensive
• Efficacy gt 90
• Rapidly effective (within hours-days)

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Indications for FMT for CDI

• For recurrent, refractory dz YES
• For severe dz arguably yes
• As first-line therapy arguably yes
• For post-C. difficile IBS - possibly

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Future Direction of FMT

• Universal donor
• Processed and frozen until use
• RePOOPulate
• Artificial stool synthetic alternative
• Indications
• Severe, complicated CDI ? 1st occurrence
• Other GI IBD, IBS, constipation
• Non-GI DM, obesity, Parkinson, MS, ITP, Autism?
• Route of administration
• LGI transplant better than UGI ?
• Safety

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Questions ?