Abstract

Strain-resolved analysis in a randomized trial of antibiotic pretreatment and maintenance dose delivery mode with fecal microbiota transplant for ulcerative colitis

Sci Rep. 2022 Apr 1;12(1):5517.doi: 10.1038/s41598-022-09307-5.

 

Byron J Smith 1 2Yvette Piceno 3Martin Zydek 4Bing Zhang 4 5Lara Aboud Syriani 6Jonathan P Terdiman 4Zain Kassam 7Averil Ma 8Susan V Lynch 4 9Katherine S Pollard 10 11 12Najwa El-Nachef 13

 
     

Author information

1Gladstone Institute of Data Science and Biotechnology, San Francisco, CA, USA.

2Department of Epidemiology and Biostatistics, University of California, San Francisco, CA, USA.

3Symbiome, Inc., San Francisco, CA, USA.

4Division of Gastroenterology, University of California, San Francisco, CA, USA.

5Division of Gastrointestinal and Liver Diseases, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.

6College of Osteopathic Medicine of the Pacific, Western University of Health Sciences, Pomona, CA, USA.

7Finch Therapeutics, Somerville, MA, USA.

8Department of Medicine, University of California, San Francisco, CA, USA.

9Benioff Center for Microbiome Medicine, University of California, San Francisco, CA, USA.

10Gladstone Institute of Data Science and Biotechnology, San Francisco, CA, USA. katherine.pollard@gladstone.ucsf.edu.

11Department of Epidemiology and Biostatistics, University of California, San Francisco, CA, USA. katherine.pollard@gladstone.ucsf.edu.

12Chan Zuckerberg Biohub, San Francisco, CA, USA. katherine.pollard@gladstone.ucsf.edu.

13Division of Gastroenterology, University of California, San Francisco, CA, USA. najwa.elnachef@ucsf.edu.

Abstract

Fecal microbiota transplant is a promising therapy for ulcerative colitis. Parameters maximizing effectiveness and tolerability are not yet clear, and it is not known how import the transmission of donor microbes to patients is. Here (clinicaltrails.gov: NCT03006809) we have tested the effects of antibiotic pretreatment and compared two modes of maintenance dose delivery, capsules versus enema, in a randomized, pilot, open-label, 2 × 2 factorial design with 22 patients analyzed with mild to moderate UC. Clinically, the treatment was well-tolerated with favorable safety profile. Of patients who received antibiotic pretreatment, 6 of 11 experienced remission after 6 weeks of treatment, versus 2 of 11 non-pretreated patients (log odds ratio: 1.69, 95% confidence interval: -0.25 to 3.62). No significant differences were found between maintenance dosing via capsules versus enema. In exploratory analyses, microbiome turnover at both the species and strain levels was extensive and significantly more pronounced in the pretreated patients. Associations were also revealed between taxonomic turnover and changes in the composition of primary and secondary bile acids. Together these findings suggest that antibiotic pretreatment contributes to microbiome engraftment and possibly clinical effectiveness, and validate longitudinal strain tracking as a powerful way to monitor the dynamics and impact of microbiota transfer.

 

 

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