title: Effects of Fecal Microbial Transplantation on Microbiome and Immunity in Simian Immunodeficiency Virus-Infected Macaques.
abstract: An altered intestinal microbiome during chronic human immunodeficiency virus (HIV) infection is associated with mucosal dysfunction, inflammation, and disease progression. We performed a preclinical evaluation of the safety and efficacy of fecal microbiota transplantation (FMT) as a potential therapeutic in HIV-infected individuals. Antiretroviral-treated, chronically simian immunodeficiency virus (SIV)-infected rhesus macaques received antibiotics followed by FMT. The greatest microbiota shift was observed after antibiotic treatment. The bacterial community composition at 2 weeks post-FMT resembled the pre-FMT community structure, although differences in the abundances of minor bacterial populations remained. Immunologically, we observed significant increases in the number of peripheral Th17 and Th22 cells and reduced CD4(+) T cell activation in gastrointestinal tissues post-FMT. Importantly, the transplant was well tolerated with no negative clinical side effects. Although this pilot study did not control for the differential contributions of antibiotic treatment and FMT to the observed results, the data suggest that FMT may have beneficial effects that should be further evaluated in larger studies.
  
  
  OBJECTIVE
  Due to the immunodeficiency and chronic inflammation that occurs during HIV infection, determination of the safety of FMT is crucial to prevent deleterious consequences if it is to be used as a treatment in the future. Here we used the macaque model of HIV infection and performed FMT on six chronically SIV-infected rhesus macaques on antiretroviral treatment. In addition to providing a preclinical demonstration of the safety of FMT in primates infected with a lentivirus, this study provided a unique opportunity to examine the relationships between alterations to the microbiome and immunological parameters. In this study, we found increased numbers of Th17 and Th22 cells as well as decreased activation of CD4(+) T cells post-FMT, and these changes correlated most strongly across all sampling time points with lower-abundance taxonomic groups and other taxonomic groups in the colon. Overall, these data provide evidence that changes in the microbiome, particularly in terms of diversity and changes in minor populations, can enhance immunity and do not have adverse consequences.
authors.affiliation: Department of Pharmaceutics, University of Washington, Seattle, Washington, USA.|Washington National Primate Research Center (WaNPRC), University of Washington, Seattle, Washington, USA.
authors.forename: Tiffany
authors.initials: T
authors.lastname: Hensley-McBain
authors.affiliation: Department of Pharmaceutics, University of Washington, Seattle, Washington, USA.|Washington National Primate Research Center (WaNPRC), University of Washington, Seattle, Washington, USA.
authors.forename: Alexander S
authors.initials: AS
authors.lastname: Zevin
authors.affiliation: Department of Pharmaceutics, University of Washington, Seattle, Washington, USA.|Washington National Primate Research Center (WaNPRC), University of Washington, Seattle, Washington, USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Manuzak
authors.affiliation: Washington National Primate Research Center (WaNPRC), University of Washington, Seattle, Washington, USA.|Department of Microbiology, University of Washington, Seattle, Washington, USA.
authors.forename: Elise
authors.initials: E
authors.lastname: Smith
authors.affiliation: Department of Pharmaceutics, University of Washington, Seattle, Washington, USA.|Washington National Primate Research Center (WaNPRC), University of Washington, Seattle, Washington, USA.
authors.forename: Jillian
authors.initials: J
authors.lastname: Gile
authors.affiliation: Department of Pharmaceutics, University of Washington, Seattle, Washington, USA.|Washington National Primate Research Center (WaNPRC), University of Washington, Seattle, Washington, USA.
authors.forename: Charlene
authors.initials: C
authors.lastname: Miller
authors.affiliation: Washington National Primate Research Center (WaNPRC), University of Washington, Seattle, Washington, USA.
authors.forename: Brian
authors.initials: B
authors.lastname: Agricola
authors.affiliation: Washington National Primate Research Center (WaNPRC), University of Washington, Seattle, Washington, USA.|Department of Microbiology, University of Washington, Seattle, Washington, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Katze
authors.affiliation: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: R Keith
authors.initials: RK
authors.lastname: Reeves
authors.affiliation: Department of Pathology and Laboratory Medicine, Emory University Hospital, Atlanta, Georgia, USA.
authors.forename: Colleen S
authors.initials: CS
authors.lastname: Kraft
authors.affiliation: Washington National Primate Research Center (WaNPRC), University of Washington, Seattle, Washington, USA.|Department of Microbiology, University of Washington, Seattle, Washington, USA.
authors.forename: Stanley
authors.initials: S
authors.lastname: Langevin
authors.affiliation: Department of Pharmaceutics, University of Washington, Seattle, Washington, USA klattnr@uw.edu.|Washington National Primate Research Center (WaNPRC), University of Washington, Seattle, Washington, USA.
authors.forename: Nichole R
authors.initials: NR
authors.lastname: Klatt
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D003106:Colon / Q000382:microbiology / Q000473:pathology; D004195:Disease Models, Animal; D000069467:Fecal Microbiota Transplantation / Q000009:adverse effects; D000069196:Gastrointestinal Microbiome / Q000187:drug effects / Q000276:immunology; D020459:Genes, rRNA; D015658:HIV Infections / Q000276:immunology / Q000382:microbiology / Q000628:therapy / Q000821:virology; D006801:Humans; D007422:Intestines / Q000166:cytology / Q000276:immunology / Q000382:microbiology; D008213:Lymphocyte Activation / Q000187:drug effects; D008253:Macaca mulatta; D010865:Pilot Projects; D012336:RNA, Ribosomal, 16S / Q000235:genetics; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000382:microbiology / Q000628:therapy*; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000276:immunology*; D058504:Th17 Cells / Q000276:immunology; D019562:Viral Load / Q000187:drug effects
chemical_list: D000900:Anti-Bacterial Agents; D012336:RNA, Ribosomal, 16S