Low Level Engraftment and Improvement following a Single Colonoscopic Administration of Fecal Microbiota to Patients with Ulcerative Colitis.
OBJECTIVE
Fecal microbiota transplantation (FMT) is an investigational treatment for diseases thought to involve alterations in the intestinal microbiota including ulcerative colitis (UC). Case reports have described therapeutic benefit of FMT in patients with UC, possibly due to changes in the microbiota. We measured the degree to which the transplanted microbiota engraft following FMT in patients with UC using a donor similarity index (DSI).


METHODS
Seven patients with mild to moderate UC (UC disease activity index scores 3-10) received a single colonoscopic administration of FMT. Metagenomic sequence data from stool were analyzed using an alignment-free comparison tool, to measure the DSI, and a phylogenetic analysis tool, to characterize taxonomic changes. Clinical, endoscopic, histologic, and fecal calprotectin outcome measures were also collected.


RESULTS
One of 5 patients from whom sequencing data were available achieved the primary endpoint of 50% donor similarity at week 4; an additional 2 patients achieved 40% donor similarity. One patient with 40% donor similarity achieved clinical and histologic remission 1 month after FMT. However, these were lost by 2-3 months, and loss correlated with a decrease in DSI. The remaining patients did not demonstrate clinical response or remission. Histology scores improved in all but 1 patient. No patients remained in remission at 3 months after FMT.


CONCLUSIONS
Following a single colonoscopic fecal transplant, a DSI of 40-50% is achieved in about two-thirds of recipients. This level of engraftment correlated with a temporary clinical improvement in only 1/5 patients. Larger sample sizes could further validate this method for measuring engraftment, and changes in transplant frequency or method might improve microbiota engraftment and efficacy.


BACKGROUND
ClinicalTrials.gov NCT01742754.
Department of Medicine, Division of Gastroenterology, University of Washington, Seattle, Washington, 98195, United States of America.
Christopher J
CJ
Damman
Department of Microbiology, University of Washington, Seattle, Washington, 98195, United States of America.
Mitchell J
MJ
Brittnacher
Department of Anatomic Pathology, University of Washington, Seattle, Washington, 98195, United States of America.
Maria
M
Westerhoff
Department of Microbiology, University of Washington, Seattle, Washington, 98195, United States of America.
Hillary S
HS
Hayden
Department of Microbiology, University of Washington, Seattle, Washington, 98195, United States of America.
Matthew
M
Radey
Department of Microbiology, University of Washington, Seattle, Washington, 98195, United States of America.
Kyle R
KR
Hager
Department of Medicine, Division of Gastroenterology, University of Washington, Seattle, Washington, 98195, United States of America.
Sara R
SR
Marquis
Department of Microbiology, University of Washington, Seattle, Washington, 98195, United States of America.
Samuel I
SI
Miller
Department of Medicine, Division of Gastroenterology, University of Washington, Seattle, Washington, 98195, United States of America.
Timothy L
TL
Zisman
D000328:Adult; D003093:Colitis, Ulcerative / Q000382:microbiology* / Q000473:pathology / Q000628:therapy*; D003106:Colon / Q000382:microbiology* / Q000473:pathology*; D003113:Colonoscopy / Q000379:methods; D005243:Feces / Q000382:microbiology*; D005260:Female; D006801:Humans; D008297:Male; D064307:Microbiota; D008875:Middle Aged; D011446:Prospective Studies; D016896:Treatment Outcome