title: Recovery of the gut microbiome following fecal microbiota transplantation.
abstract: Clostridium difficile infection is one of the most common health care-associated infections, and up to 40% of patients suffer from recurrence of disease following standard antibiotic therapy. Recently, fecal microbiota transplantation (FMT) has been successfully used to treat recurrent C. difficile infection. It is hypothesized that FMT aids in recovery of a microbiota capable of colonization resistance to C. difficile. However, it is not fully understood how this occurs. Here we investigated changes in the fecal microbiota structure following FMT in patients with recurrent C. difficile infection, and imputed a hypothetical functional profile based on the 16S rRNA profile using a predictive metagenomic tool. Increased relative abundance of Bacteroidetes and decreased abundance of Proteobacteria were observed following FMT. The fecal microbiota of recipients following transplantation was more diverse and more similar to the donor profile than the microbiota prior to transplantation. Additionally, we observed differences in the imputed metagenomic profile. In particular, amino acid transport systems were overrepresented in samples collected prior to transplantation. These results suggest that functional changes accompany microbial structural changes following this therapy. Further identification of the specific community members and functions that promote colonization resistance may aid in the development of improved treatment methods for C. difficile infection.
  
  
  OBJECTIVE
  Within the last decade, Clostridium difficile infection has surpassed other bacterial infections to become the leading cause of nosocomial infections. Antibiotic use, which disrupts the gut microbiota and its capability in providing colonization resistance against C. difficile, is a known risk factor in C. difficile infection. In particular, recurrent C. difficile remains difficult to treat with standard antibiotic therapy. Fecal microbiota transplantation (FMT) has provided a successful treatment method for some patients with recurrent C. difficile infection, but its mechanism and long-term effects remain unknown. Our results provide insight into the structural and potential metabolic changes that occur following FMT, which may aid in the development of new treatment methods for C. difficile infection.
authors.affiliation: Department of Internal Medicine, Division of Infectious Diseases, Department of Microbiology and Immunology, University of Michigan, Ann Arbor, Michigan, USA;
authors.forename: Anna M
authors.initials: AM
authors.lastname: Seekatz
authors.affiliation: Essentia Health, Department of Gastroenterology, Duluth, Minnesota, USA;
authors.forename: Johannes
authors.initials: J
authors.lastname: Aas
authors.affiliation: Essentia Institute of Rural Health, Duluth, Minnesota, USA;
authors.forename: Charles E
authors.initials: CE
authors.lastname: Gessert
authors.affiliation: Essentia Health, Department of Gastroenterology, Duluth, Minnesota, USA;
authors.forename: Timothy A
authors.initials: TA
authors.lastname: Rubin
authors.affiliation: Essentia Institute of Rural Health, Duluth, Minnesota, USA;
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Saman
authors.affiliation: St. Luke's Hospital, Section of Infectious Diseases, Duluth, Minnesota, USA.
authors.forename: Johan S
authors.initials: JS
authors.lastname: Bakken
authors.affiliation: Department of Internal Medicine, Division of Infectious Diseases, Department of Microbiology and Immunology, University of Michigan, Ann Arbor, Michigan, USA; youngvi@med.umich.edu.
authors.forename: Vincent B
authors.initials: VB
authors.lastname: Young
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001419:Bacteria / Q000145:classification / Q000235:genetics / Q000302:isolation & purification*; D001691:Biological Therapy; D016360:Clostridioides difficile / Q000502:physiology*; D003015:Clostridium Infections / Q000382:microbiology / Q000628:therapy*; D005243:Feces / Q000382:microbiology*; D005260:Female; D041981:Gastrointestinal Tract / Q000382:microbiology; D006801:Humans; D008297:Male; D064307:Microbiota; D008875:Middle Aged; D008969:Molecular Sequence Data; D010802:Phylogeny