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

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.

Application of Microbiome Management in Therapy for Clostridioides difficile Infections: From Fecal Microbiota Transplantation to Probiotics to Microbiota-Preserving Antimicrobial Agents

“…To simplify the influence of FMT on gut microbiota, studies among specific populations, such as groups with malignancy or inflammatory bowel disease, are not discussed in this review [ 16 ]. Since the poor bacterial diversity is correlated with rCDIs in clinical patients, the efficacy of FMT in preventing rCDIs has been correlated with the restoration of the disturbed and poor diversity of gut microbiota due to the disruption by antibiotic exposures [ 17 , 18 ], for example, replanting the genera of Bacteroidetes [ 16 , 19 , 20 , 21 , 22 , 23 , 24 , 25 ], Firmicutes [ 23 , 25 ], Faecalibacterium [ 16 , 26 ], or Bifidobacterium [ 27 ], and conveniently decreasing Proteobacteria [ 22 , 25 , 28 ], Enterobacteriaceae [ 29 , 30 ], or bacteria harboring antibiotic-resistant genes within the microbiota [ 25 ].…”

“…The diverse change in microbiota after FMT was noticed, which might depend on the different composition of microbiota of the donor population, different donor ages, or different FMT methods [ 22 , 23 , 27 , 31 , 32 ]. For all successful FMT treatments with the resolution of rCDI symptoms and a negative C. difficile toxin test within 4–12 weeks after FMT, the genomic analysis of donor microbiota showed that the Bacteroidetes-to-Fermicutes ratio did not reveal a significant difference among donors with different ages [ 32 ].…”

“…The colonization of Bacteroidetes [ 16 , 19 , 20 , 21 , 22 , 23 , 24 , 25 ], Firmicutes [ 23 , 25 ], Faecalibacterium [ 16 , 26 ], or Bifidobacterium [ 27 ] were found to be decreased during the initial CDIs and rCDIs after successful FMT. In a cohort with a long-term (up to 409 days) follow-up, all patients who were clinically recovered and free of CDIs were characterized by increased members of the genera Bacteroides, Parabacteroides, and Faecalibacterium throughout the year in their fecal microbiota [ 19 ].…”

“…No matter the composition of donor’s microbiota or the ways of performing FMT, donor-derived Bacteroidetes, Firmicutes, or Bifidobacterium can colonize rCDI patients who were treated successfully with FMT for more than one year, and accordingly, FMT may have long-term consequences for the recipient’s microbiota and health [ 22 , 23 , 24 , 27 , 31 ].…”

Novel strain of Pseudoruminococcus massiliensis possesses traits important in gut adaptation and host-microbe interactions

“… 6 , 8 The potential of different species and strains within the donor´s microbiota to colonize the recipient gut is affected by multiple factors, including the properties of individual strains and co-transferred bacteria as well as the recipient´s endogenous microbiota and niche opportunity in the new ecosystem. 9–12 The key bacterial species associated with a positive outcome upon FMT are yet to be identified.…”