Cultivation and Genomics Prove Long-Term Colonization of Donor's Bifidobacteria in Recurrent Clostridioides difficile Patients Treated With Fecal Microbiota Transplantation

Hanne Jouhten; Aki Ronkainen; Juhani Aakko; Seppo Salminen; Eero Mattila; Perttu Arkkila; Reetta Satokari

doi:10.3389/fmicb.2020.01663

Cultivation and Genomics Prove Long-Term Colonization of Donor's Bifidobacteria in Recurrent Clostridioides difficile Patients Treated With Fecal Microbiota Transplantation

Front Microbiol. 2020 Jul 15:11:1663. doi: 10.3389/fmicb.2020.01663. eCollection 2020.

Authors

Hanne Jouhten¹, Aki Ronkainen¹, Juhani Aakko², Seppo Salminen², Eero Mattila³, Perttu Arkkila⁴, Reetta Satokari¹

Affiliations

¹ Human Microbiome Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
² Functional Foods Forum, Faculty of Medicine, University of Turku, Turku, Finland.
³ Department of Infectious Diseases, Helsinki University Hospital, Helsinki, Finland.
⁴ Department of Gastroenterology, Helsinki University Hospital, Helsinki, Finland.

Abstract

Fecal microbiota transplantation (FMT) is an effective treatment for recurrent Clostridioides difficile infection (rCDI) and it's also considered for treating other indications. Metagenomic studies have indicated that commensal donor bacteria may colonize FMT recipients, but cultivation has not been employed to verify strain-level colonization. We combined molecular profiling of Bifidobacterium populations with cultivation, molecular typing, and whole genome sequencing (WGS) to isolate and identify strains that were transferred from donors to recipients. Several Bifidobacterium strains from two donors were recovered from 13 recipients during the 1-year follow-up period after FMT. The strain identities were confirmed by WGS and comparative genomics. Our results show that specific donor-derived bifidobacteria can colonize rCDI patients for at least 1 year, and thus FMT may have long-term consequences for the recipient's microbiota and health. Conceptually, we demonstrate that FMT trials combined with microbial profiling can be used as a platform for discovering and isolating commensal strains with proven colonization capacity for potential therapeutic use.

Keywords: C. difficile; comparative genomics; intestinal microbiota; next-generation probiotics; stool transplantation; strain tracking; therapeutic bacteria; whole genome sequencing.