Loss of sex and age driven differences in the gut microbiome characterize arthritis-susceptible 0401 mice but not arthritis-resistant 0402 mice.

PloS One
Andres GomezVeena Taneja

Abstract

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. 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. We have demonstrated for the first time that HLA genes in association with the gut microbiome may determi...Continue Reading

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Datasets Mentioned

BETA
SRA043819

Methods Mentioned

BETA
Transgenic
flow cytometry

Software Mentioned

ca
R project
SAS
R
pwr
Primer
E PRIMER
ANOSIM
Mothur Perl scripts
Blastn

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