title: Loss of sex and age driven differences in the gut microbiome characterize arthritis-susceptible 0401 mice but not arthritis-resistant 0402 mice.
abstract: BACKGROUND
  HLA-DRB1 0401 is associated with susceptibility, while HLA-DRB1 0402 is associated with resistance to developing rheumatoid arthritis (RA) and collagen-induced arthritis in humans and transgenic mice respectively. The influence of gut-joint axis has been suggested in RA, though not yet proven.
  
  
  RESULTS
  We have used HLA transgenic mice carrying arthritis susceptible and -resistant HLA-DR genes to explore if genetic factors and their interaction with gut flora gut can be used to predict susceptibility to develop arthritis. Pyrosequencing of the 16S rRNA gene from the fecal microbiomes of DRB1 0401 and DRB1 0402 transgenic mice revealed that the guts of 0401 mice is dominated by a Clostridium-like bacterium, whereas the guts of 0402 mice are enriched for members of the Porphyromonadaceae family and Bifidobacteria. DRB1 0402 mice harbor a dynamic sex and age-influenced gut microbiome while DRB1 0401 mice did not show age and sex differences in gut microbiome even though they had altered gut permeability. Cytokine transcripts, measured by rtPCR, in jejuna showed differential TH17 regulatory network gene transcripts in 0401 and 0402 mice.
  
  
  CONCLUSIONS
  We have demonstrated for the first time that HLA genes in association with the gut microbiome may determine the immune environment and that the gut microbiome might be a potential biomarker as well as contributor for susceptibility to arthritis. Identification of pathogenic commensal bacteria would provide new understanding of disease pathogenesis, thereby leading to novel approaches for therapy.
authors.affiliation: Institute for Genomic Biology, University of Illinois, Urbana, Illinois, United States of America.
authors.forename: Andres
authors.initials: A
authors.lastname: Gomez
authors.forename: David
authors.initials: D
authors.lastname: Luckey
authors.forename: Carl J
authors.initials: CJ
authors.lastname: Yeoman
authors.forename: Eric V
authors.initials: EV
authors.lastname: Marietta
authors.forename: Margret E
authors.initials: ME
authors.lastname: Berg Miller
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Murray
authors.forename: Bryan A
authors.initials: BA
authors.lastname: White
authors.forename: Veena
authors.initials: V
authors.lastname: Taneja
mesh_terms: D000367:Age Factors; D000818:Animals; D001168:Arthritis / Q000235:genetics / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology*; D018925:Chemokines / Q000235:genetics / Q000378:metabolism; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D005243:Feces / Q000382:microbiology; D005260:Female; D020022:Genetic Predisposition to Disease; D059811:HLA-DRB1 Chains / Q000276:immunology*; D007422:Intestines / Q000382:microbiology*; D008297:Male; D054892:Metagenome; D051379:Mice; D008822:Mice, Transgenic; D012336:RNA, Ribosomal, 16S / Q000737:chemistry; D017422:Sequence Analysis, DNA; D012737:Sex Factors
chemical_list: D018925:Chemokines; D016207:Cytokines; D059811:HLA-DRB1 Chains; C553505:HLA-DRB1*04:01 antigen; C553506:HLA-DRB1*04:02 antigen; D012336:RNA, Ribosomal, 16S