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

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