Fecal Microbiota Transplant Flashcards
FMT
Introduction of fecal suspension derived from a healthy donor into the GI tract of a diseased individual
Goals of FMT
- Restore phylogenetic diversity and therefore physiological functions
- Replace/inhibit pathogenic species
FMTs started
1700 years ago in China for severe diarrhea + 4th century for severe diarrhea
Yellow soup
Infant feces used to treat diarrheal illness in the 16th century
Growth of FMT in recent years due to
1) Global C. difficile epidemic (CDI)
2) Growing appreciation of the complexity of the GI microbiome and its role in health and disease
Current indication for FMT
CDI
Future indications for FMT
UC (curable in some) + CD (supporting role?)
Antibiotics for CDI
Metronidazole, Vancomycin, Fidaxomicin, Rifaximin
Downfalls of CDI antibiotic therapy (4)
Further microbial damage + reoccurrence rate of 20% + rising reoccurrence rate with each episode + do not correct normal microbiome
CDI symptoms
fever, abdominal cramps, diarrhea
CDI mechanism
Endospores survive acidity and reach intestines and grows in colon –> produces Toxin A and B to cause mucosal damage –> Pseudomembranous colitis where yellow plaques form over damaged epithelium –> antibiotics make it worse by altering normal microbiota and causing dysbiosis
CDI is the
Most common infectious cause of nosocomial diarrhea
CDI epidemic
2000-2002: number of cases doubled and severity, death, and surgeries increased
CDI epidemic was associated with…
Quinolone use and hypervirulent strains
Cure rate of FMTs
85-90% in case series
Efficacy of FMT in CDI
Clinical trial: First round 81% and second 94% (30% vancomycin)
OTUs relative abundance in FMT
Switch from a recipient to donor microbiome
IBD and FMT
Has had a systemic review and meta analysis done with 18 studies and 1 randomised –> 122 patient (79 UC, 39 CD, and 4 unclassified)
Remission of IBD in Systemic Review
45% had clinical remission: 36% in cohort studies, 22% in UC, and 61% in CD
Conclusions of IBD analysis
Study bias and more randomized studies needed with clinical and microbiological data needed + no serious safety concerns
How to FMT
- Donor selection
- Donor screening
- Stool collection and prep
- Patient prep and stool administration
Donor selection
Unrelated member or family and friends: must be healthy and devoid of transmissible or microbiota associated disease (IBS, obesity, constipation, GI malignancy) + no recent antibiotics
Only ___ candidates for FMT are selected when screened
30%
Types of screening for donor
Medical interview + medical history and exam + blood + stool
Stool preparation
Fresh stool blended in saline solution –> filter out larger particles –> place into barium enema kit or make capsules…
Stool must be delivered for processing
Within hour
Freezing of stool
Can be frozen after processing in stool bank
No consensus for
FMT preparation, processing, patient prep, or rout of administration
Patient prep
Stop antibiotics (24-72 hours before), colonoscopy prep night before
Main routes of FMT
Retention enema, colonoscopy, naso-duodenal infusion, pills
Safety of FMT
Generally well tolerated
Risks of FMT (3)
Infection, microbiota associated disease, complication of procedure
Most common symptom day of infection
Diarrhea
Frozen stool banks
Permit post donation screening and no “same day delivery” + shown efficacious
Next Generation FMT
Starting up in CDI as standardised pharmaceutical grade, prep of beneficial mix of bacteria
Next Generation FMT composition
Can be whole microbiome or few beneficial strains
Example of Next Generation FMT
RBX2660 (87% success in Phase II trails)
