Selective estrogen receptor modulator lasofoxifene suppresses spondyloarthritis manifestation and affects characteristics of gut microbiota in zymosan-induced SKG mice

Abstract

Ankylosing spondylitis is a male-predominant disease and previous study revealed that estrogens have an anti-inflammatory effect on the spondyloarthritis (SpA) manifestations in zymosan-induced SKG mice. This study aimed to evaluate the effect of selective estrogen receptor modulator (SERM) lasofoxifene (Laso) on disease activity of SpA. Mice were randomized into zymosan-treated, zymosan+17 beta-estradiol (E2)-treated, and zymosan+Laso-treated groups. Arthritis was assessed by F-18-fluorodeoxyglucose (F-18-FDG) small-animal positron emission tomography/computed tomography and bone mineral density (BMD) was measured. Fecal samples were collected and 16S ribosomal RNA gene sequencing was used to determine gut microbiota differences. Both zymosan+E2-treated mice and zymosan+Laso-treated mice showed lower arthritis clinical scores and lower F-18-FDG uptake than zymosan-treated mice. BMD was significantly higher in zymosan+E2-treated mice and zymosan+Laso-treated mice than zymosan-treated mice, respectively. Fecal calprotectin levels were significantly elevated at 8 weeks after zymosan injection in zymosan-treated mice, but it was not significantly changed in zymosan+E2-treated mice and zymosan+Laso-treated mice. Gut microbiota diversity of zymosan-treated mice was significantly different from zymosan+E2-treated mice and zymosan+Laso-treated mice, respectively. There was no significant difference in gut microbiota diversity between zymosan+E2-treated mice and zymosan+Laso -treated mice. Laso inhibited joint inflammation and enhanced BMD in SKG mice, a model of SpA. Laso also affected the composition and biodiversity of gut microbiota. This study provides new knowledge regarding that selected SpA patients could benefit from SERM treatment.