Asquith M, et al. - In this investigation, researchers studied whether ankylosing spondylitis (AS) and rheumatoid arthritis (RA)-associated HLA alleles in healthy individuals influence the gut microbiome to support the assumption that they influence the risk of developing AS and RA through effects on the gut microbiome. Five hundred sixty-eight samples from 6 intestinal sites from 107 otherwise unrelated healthy subjects and stool samples from 696 twin pairs from the TwinsUK cohort were collected. According to results, there was an association between HLA-B27 genotype, and RA-risk HLA-DRB1 alleles, and overall microbial composition. The TwinsUK cohort stool samples replicated these associations. This investigation reveals that changes in the composition of the intestinal microbiome seen in AS and RA are at least partially due to effects on the gut microbiome of HLA-B27 and –DRB1. These findings support the assumption that HLA alleles operate by interacting with the intestinal microbiome to cause or increase the risk of these diseases, and suggest that microbiome-targeted therapies may be effective in their prevention and/or treatment.