[HLA-B27 alters gut microbial composition and promotes susceptibility to intestinal inflammation]

Objective This study aimed to investigate the impact of human leukocyte antigen B27 (HLA-B27)/β2m gene expression on the gut microbiota and metabolites, and to elucidate its role in the pathogenesis of spinal arthritis (SpA)-associated intestinal inflammation. Methods Transgenic mice expressing HLA-B27/β2m without spontaneous inflammation were employed. Integrated multi-omics analyses, including metagenomics and metabolomics, were conducted to profile microbial and metabolic changes at prenatal, early colonization, and stable colonization stages. Inflammatory susceptibility was further assessed using a dextran sulfate sodium (DSS)-induced colitis model. Results Expression of HLA-B27/β2m significantly altered the gut microbiota structure, promoting the expansion of Gram-negative bacteria and inhibiting Gram-positive populations. Metabolomic profiling revealed enhanced arachidonic acid metabolism, elevated levels of pro-inflammatory metabolites such as prostaglandins, and a reduction in anti-inflammatory flavonoids. These findings collectively indicated a pro-inflammatory intestinal microenvironment, which was corroborated by exacerbated colitis upon DSS challenge in animal models. Conclusion The HLA-B27/β2m gene modulates gut microbial composition and metabolic balance, predisposing the intestine to inflammatory responses. These results provide novel mechanistic insights into the "gut-joint axis" in SpA pathogenesis.