Among patients with ankylosing spondylitis (AS) and rheumatoid arthritis (RA), changes in intestinal microbiome composition are the result of the effects of human leukocyte antigen (HLA)-B27 and HLA-DRB1 on the gut microbiome, according to study results published in Arthritis & Rheumatology. The results support the hypothesis that HLA alleles may cause or increase the risk for AS or RA by interaction with the intestinal microbiome.

The study included 568 stool and biopsy samples from 6 intestinal sites collected from 107 participants (61 female; age range, 40-75 years). In addition, the study included stool samples from 1392 twins from the TwinsUK cohort. Researchers performed microbiome profiling by sequencing the 16S ribosomal RNA bacterial marker gene. They used the Illumina CoreExome single-nucleotide polymorphism microarray to perform genotyping of all participants. HLA genotypes were imputed using these data.

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Researchers found a significant association between body mass index (BMI) and microbiome composition (P =.0022), primarily driven by the differences seen in underweight participants (BMI <18.5). They also found significant differences in the microbiomes of individuals based on sex (P =.0004).

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After adjusting for BMI and sex, researchers found associations between the overall microbial composition and between both the HLA-B27 genotype and HLA-DRB1 RA risk allele (P =.0002 and P =.00001, respectively). Using the stool samples from the TwinsUK cohort, both associations were replicated (P =.023 and P =.033, respectively).

“The data presented here support the need for further research in this field, including investigation of whether manipulation of the gut microbiome may be therapeutic or potentially capable of preventing AS or RA in at-risk [individuals],” the researchers wrote.


Asquith M, Sternes PR, Costello M-E, et al. HLA alleles associated with risk of ankylosing spondylitis and rheumatoid arthritis influence the gut microbiome [published online April 30, 2019]. Arthritis Rheumatol. doi:10.1002/art.40917