title: Community dynamics drive punctuated engraftment of the fecal microbiome following transplantation using freeze-dried, encapsulated fecal microbiota.
abstract: Fecal microbiota transplantation (FMT) is a highly effective treatment of recurrent and recalcitrant Clostridium difficile infection (rCDI). In a recent study oral-delivery of encapsulated, freeze-dried donor material, resulted in comparable rates of cure to colonoscopic approaches. Here we characterize shifts in the fecal bacterial community structure of patients treated for rCDI using encapsulated donor material. Prior to FMT, patient fecal samples showed declines in diversity and abundance of Firmicutes and Bacteroidetes, with concurrent increases in members of the Proteobacteria, specifically Enterobacteriaceae. Moreover, patients who experienced recurrence of CDI within the 2-month clinical follow-up had greater abundances of Enterobacteriaceae and did not show resolution of dysbioses. Despite resolution of rCDI following oral-administration of encapsulated fecal microbiota, community composition was slow to return to a normal donor-like assemblage. Post-FMT taxa within the Firmicutes showed rapid increases in relative abundance and did not vary significantly over time. Conversely, Bacteroidetes taxa only showed significant increases in abundance after one month post-FMT, corresponding to significant increases in the community attributable to the donors. Changes in the associations among dominant OTUs were observed at days, weeks, and months post-FMT, suggesting shifts in community dynamics may be related to the timing of increases in abundance of specific taxa. Administration of encapsulated, freeze-dried, fecal microbiota to rCDI patients resulted in restoration of bacterial diversity and resolution of dysbiosis. However, shifts in the fecal microbiome were incremental rather than immediate, and may be driven by changes in community dynamics reflecting changes in the host environment.
authors.affiliation: a BioTechnology Institute , University of Minnesota , St. Paul , Minnesota , USA.
authors.forename: Christopher
authors.initials: C
authors.lastname: Staley
authors.affiliation: b Division of Gastroenterology , Department of Medicine , University of Minnesota , Minneapolis , Minnesota , USA.
authors.forename: Byron P
authors.identifier: 0000-0001-5081-3761
authors.initials: BP
authors.lastname: Vaughn
authors.affiliation: b Division of Gastroenterology , Department of Medicine , University of Minnesota , Minneapolis , Minnesota , USA.
authors.forename: Carolyn T
authors.initials: CT
authors.lastname: Graiziger
authors.affiliation: a BioTechnology Institute , University of Minnesota , St. Paul , Minnesota , USA.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Singroy
authors.affiliation: a BioTechnology Institute , University of Minnesota , St. Paul , Minnesota , USA.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Hamilton
authors.affiliation: c Department of Food Science and Nutrition , University of Minnesota , St. Paul , Minnesota , USA.
authors.forename: Dan
authors.initials: D
authors.lastname: Yao
authors.affiliation: c Department of Food Science and Nutrition , University of Minnesota , St. Paul , Minnesota , USA.
authors.forename: Chi
authors.initials: C
authors.lastname: Chen
authors.affiliation: a BioTechnology Institute , University of Minnesota , St. Paul , Minnesota , USA.|b Division of Gastroenterology , Department of Medicine , University of Minnesota , Minneapolis , Minnesota , USA.
authors.forename: Alexander
authors.initials: A
authors.lastname: Khoruts
authors.affiliation: a BioTechnology Institute , University of Minnesota , St. Paul , Minnesota , USA.|d Department of Soil, Water and Climate , University of Minnesota , St. Paul , Minnesota , USA.
authors.forename: Michael J
authors.identifier: 0000-0001-8779-2781
authors.initials: MJ
authors.lastname: Sadowsky
mesh_terms: D000284:Administration, Oral; D041963:Bacteroidetes / Q000302:isolation & purification; D001647:Bile Acids and Salts / Q000032:analysis; D044822:Biodiversity; D002214:Capsules; D002853:Chromatography, Liquid; D003015:Clostridium Infections / Q000628:therapy; D004269:DNA, Bacterial / Q000235:genetics; D000069467:Fecal Microbiota Transplantation; D005243:Feces / Q000382:microbiology; D000068536:Bacillota / Q000302:isolation & purification; D005500:Follow-Up Studies; D005612:Freeze Drying; D000069196:Gastrointestinal Microbiome; D006801:Humans; D007422:Intestines / Q000382:microbiology*; D013058:Mass Spectrometry; D020560:Proteobacteria / Q000302:isolation & purification; D012008:Recurrence; D017422:Sequence Analysis, DNA; D016896:Treatment Outcome
chemical_list: D001647:Bile Acids and Salts; D002214:Capsules; D004269:DNA, Bacterial
keywords: 16S rRNA; Capsule-delivered FMT; Clostridium difficile; cure; fecal microbial transplantation; microbial community structure; next-generation sequencing