title: A Novel Microbiome Therapeutic Increases Gut Microbial Diversity and Prevents Recurrent Clostridium difficile Infection.
abstract: Patients with recurrent Clostridium difficile infection (CDI) have a ≥60% risk of relapse, as conventional therapies do not address the underlying gastrointestinal dysbiosis. This exploratory study evaluated the safety and efficacy of bacterial spores for preventing recurrent CDI.
  
  
  
  Stool specimens from healthy donors were treated with ethanol to eliminate pathogens. The resulting spores were fractionated and encapsulated for oral delivery as SER-109. Following their response to standard-of-care antibiotics, patients in cohort 1 were treated with SER-109 on 2 consecutive days (geometric mean dose, 1.7 × 10(9) spores), and those in cohort 2 were treated on 1 day (geometric mean dose, 1.1 × 10(8) spores). The primary efficacy end point was absence of C. difficile-positive diarrhea during an 8-week follow-up period. Microbiome alterations were assessed.
  
  
  
  Thirty patients (median age, 66.5 years; 67% female) were enrolled, and 26 (86.7%) met the primary efficacy end point. Three patients with early, self-limiting C. difficile-positive diarrhea did not require antibiotics and tested negative for C. difficile at 8 weeks; thus, 96.7% (29 of 30) achieved clinical resolution. In parallel, gut microbiota rapidly diversified, with durable engraftment of spores and no outgrowth of non-spore-forming bacteria found after SER-109 treatment. Adverse events included mild diarrhea, abdominal pain, and nausea.
  
  
  
  SER-109 successfully prevented CDI and had a favorable safety profile, supporting a novel microbiome-based intervention as a potential therapy for recurrent CDI.
authors.affiliation: Mayo Clinic, Rochester, Minnesota.
authors.forename: Sahil
authors.initials: S
authors.lastname: Khanna
authors.affiliation: Mayo Clinic, Rochester, Minnesota.
authors.forename: Darrell S
authors.initials: DS
authors.lastname: Pardi
authors.affiliation: Miriam Hospital, Women's Medicine Collaborative, Providence, Rhode Island.
authors.forename: Colleen R
authors.initials: CR
authors.lastname: Kelly
authors.affiliation: Emory University School of Medicine, Atlanta, Georgia.
authors.forename: Colleen S
authors.initials: CS
authors.lastname: Kraft
authors.affiliation: Emory University School of Medicine, Atlanta, Georgia.
authors.forename: Tanvi
authors.initials: T
authors.lastname: Dhere
authors.affiliation: Seres Therapeutics, Cambridge.
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Henn
authors.affiliation: Seres Therapeutics, Cambridge.
authors.forename: Mary-Jane
authors.initials: MJ
authors.lastname: Lombardo
authors.affiliation: Seres Therapeutics, Cambridge.
authors.forename: Marin
authors.initials: M
authors.lastname: Vulic
authors.affiliation: Seres Therapeutics, Cambridge.
authors.forename: Toshiro
authors.initials: T
authors.lastname: Ohsumi
authors.affiliation: Seres Therapeutics, Cambridge.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Winkler
authors.affiliation: Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: Christina
authors.initials: C
authors.lastname: Pindar
authors.affiliation: Seres Therapeutics, Cambridge.
authors.forename: Barbara H
authors.initials: BH
authors.lastname: McGovern
authors.affiliation: Seres Therapeutics, Cambridge.
authors.forename: Roger J
authors.initials: RJ
authors.lastname: Pomerantz
authors.affiliation: Seres Therapeutics, Cambridge.
authors.forename: John G
authors.initials: JG
authors.lastname: Aunins
authors.affiliation: Seres Therapeutics, Cambridge.
authors.forename: David N
authors.initials: DN
authors.lastname: Cook
authors.affiliation: Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: Elizabeth L
authors.initials: EL
authors.lastname: Hohmann
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001691:Biological Therapy / Q000009:adverse effects / Q000379:methods*; D016360:Clostridioides difficile / Q000254:growth & development*; D003015:Clostridium Infections / Q000517:prevention & control*; D003967:Diarrhea / Q000517:prevention & control; D005260:Female; D000069196:Gastrointestinal Microbiome; D041981:Gastrointestinal Tract / Q000382:microbiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D055502:Secondary Prevention / Q000379:methods*; D055815:Young Adult
keywords: Clostridium difficile infection; Clostridium difficile treatment; dysbiosis; microbiome; vancomycin-resistant Enterococcus