title: Colonization potential to reconstitute a microbe community in patients detected early after fecal microbe transplant for recurrent C. difficile.
abstract: BACKGROUND
  Fecal microbiota transplants (FMT) are an effective treatment for patients with gut microbe dysbiosis suffering from recurrent C. difficile infections. To further understand how FMT reconstitutes the patient's gut commensal microbiota, we have analyzed the colonization potential of the donor, recipient and recipient post transplant fecal samples using transplantation in gnotobiotic mice.
  
  
  RESULTS
  A total of nine samples from three human donors, recipient's pre and post FMT were transplanted into gnotobiotic mice. Microbiome analysis of three donor fecal samples revealed the presence of a high relative abundance of commensal microbes from the family Bacteriodaceae and Lachnospiraceae that were almost absent in the three recipient pre FMT fecal samples (<0.01%). The microbe composition in gnotobiotic mice transplanted with the donor fecal samples was similar to the human samples. The recipient samples contained Enterobacteriaceae, Lactobacillaceae, Enterococcaceae in relative abundance of 43, 11, 8%, respectively. However, gnotobiotic mice transplanted with the recipient fecal samples had an average relative abundance of unclassified Clostridiales of 55%, approximately 7000 times the abundance in the recipient fecal samples prior to transplant. Microbiome analysis of fecal samples from the three patients early (2-4 weeks) after FMT revealed a microbe composition with the relative abundance of both Bacteriodaceae and Lachnospiraceae that was approximately 7% of that of the donor. In contrast, gnotobioitc mice transplanted with the fecal samples obtained from the three at early times post FMT revealed increases in the relative abundance of Bacteriodaceae and Lachnospiraceae microbe compositions to levels similar to the donor fecal samples. Furthermore, the unclassified Clostridiales in the recipient samples post FMT was reduced to an average of 10%.
  
  
  CONCLUSIONS
  We have used transplantation into gnotobiotic mice to evaluate the colonization potential of microbiota in FMT patients early after transplant. The commensal microbes present at early times post FMT out competed non-commensal microbes (e.g. such as unclassified Clostridiales) for niche space. The selective advantage of these commensal microbes to occupy niches in the gastrointestinal tract helps to explain the success of FMT to reconstitute the gut microbe community of patients with recurrent C. difficile infections.
authors.affiliation: Center for Clinical and Translational Sciences, University of Alabama at Birmingham, Birmingham, AL, 35294, USA.
authors.forename: Ranjit
authors.initials: R
authors.lastname: Kumar
authors.affiliation: Department of Pathology, University of Alabama at Birmingham, Birmingham, AL, 35294, USA.
authors.forename: Craig L
authors.initials: CL
authors.lastname: Maynard
authors.affiliation: Department of Cell, Developmental and Integrative Biology, University of Alabama at Birmingham, 1918 University Blvd. MCLM 680, Birmingham, AL, 35294, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Eipers
authors.affiliation: Department of Genetics and Heflin Center for Genomic Science, University of Alabama at Birmingham, Birmingham, AL, 35294, USA.
authors.forename: Kelly T
authors.initials: KT
authors.lastname: Goldsmith
authors.affiliation: Center for Clinical and Translational Sciences, University of Alabama at Birmingham, Birmingham, AL, 35294, USA.|Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL, 35294, USA.
authors.forename: Travis
authors.initials: T
authors.lastname: Ptacek
authors.affiliation: Division of Infectious Disease, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, 35294, USA.
authors.forename: J Aaron
authors.initials: JA
authors.lastname: Grubbs
authors.affiliation: Division of Infectious Disease, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, 35294, USA.
authors.forename: Paula
authors.initials: P
authors.lastname: Dixon
authors.affiliation: Department of Pathology, University of Alabama at Birmingham, Birmingham, AL, 35294, USA.
authors.forename: Donna
authors.initials: D
authors.lastname: Howard
authors.affiliation: Department of Genetics and Heflin Center for Genomic Science, University of Alabama at Birmingham, Birmingham, AL, 35294, USA.
authors.forename: David K
authors.initials: DK
authors.lastname: Crossman
authors.affiliation: Department of Genetics and Heflin Center for Genomic Science, University of Alabama at Birmingham, Birmingham, AL, 35294, USA.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Crowley
authors.affiliation: Department of Pathology, University of Alabama at Birmingham, Birmingham, AL, 35294, USA.
authors.forename: William H
authors.initials: WH
authors.lastname: Benjamin
authors.affiliation: Center for Clinical and Translational Sciences, University of Alabama at Birmingham, Birmingham, AL, 35294, USA.|Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL, 35294, USA.
authors.forename: Elliot J
authors.initials: EJ
authors.lastname: Lefkowitz
authors.affiliation: Department of Pathology, University of Alabama at Birmingham, Birmingham, AL, 35294, USA.
authors.forename: Casey T
authors.initials: CT
authors.lastname: Weaver
authors.affiliation: Division of Infectious Disease, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, 35294, USA.
authors.forename: J Martin
authors.initials: JM
authors.lastname: Rodriguez
authors.affiliation: Department of Cell, Developmental and Integrative Biology, University of Alabama at Birmingham, 1918 University Blvd. MCLM 680, Birmingham, AL, 35294, USA. caseym@uab.edu.
authors.forename: Casey D
authors.initials: CD
authors.lastname: Morrow
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D001419:Bacteria / Q000145:classification / Q000235:genetics / Q000254:growth & development* / Q000302:isolation & purification; D016360:Clostridioides difficile / Q000502:physiology*; D003015:Clostridium Infections / Q000382:microbiology / Q000628:therapy*; D000069467:Fecal Microbiota Transplantation; D005260:Female; D000069196:Gastrointestinal Microbiome; D041981:Gastrointestinal Tract / Q000382:microbiology*; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL