{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T04:58:53Z","timestamp":1780894733467,"version":"3.54.1"},"reference-count":64,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T00:00:00Z","timestamp":1780876800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Ankylosing spondylitis (AS) is a chronic immune-mediated inflammatory disease that primarily affects the axial skeleton and entheseal structures. Although the role of HLA-B27 is well established, AS pathogenesis is multifactorial, and accumulating evidence suggests that disruption of intestinal homeostasis and the gut\u2013joint axis may contribute to disease pathobiology. AS-associated gut dysbiosis is characterized by reduced microbial diversity and compositional alterations that may be associated with mucosal immune activation, increased intestinal permeability, and systemic inflammatory priming. Mechanistically, altered microbial signals and barrier dysfunction may converge on key immunological pathways, including the IL-23\/IL-17 axis, and may promote the activation or trafficking of innate-like lymphocytes, such as MAIT cells, \u03b3\u03b4 T cells, and ILC3s, thereby contributing to inflammation and abnormal bone remodeling. In addition to community structure, microbial metabolites, including short-chain fatty acids and tryptophan-derived indole metabolites, help regulate epithelial integrity and immunoregulatory homeostasis; their perturbation may favor pro-inflammatory immune programs relevant to AS. This review summarizes recent evidence on dysbiosis, barrier dysfunction, and immunometabolic signaling in the gut\u2013joint axis, while critically distinguishing established immune-targeted therapies from experimental microbiota-directed and combination strategies.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1809165","type":"journal-article","created":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T04:23:03Z","timestamp":1780892583000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Mechanistic insights into how gut homeostasis and immune-system crosstalk shape ankylosing spondylitis"],"prefix":"10.3389","volume":"17","author":[{"given":"Jiawen","family":"Li","sequence":"first","affiliation":[{"name":"Gansu University of Traditional Chinese Medicine","place":["Lanzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingwen","family":"Xie","sequence":"additional","affiliation":[{"name":"Gansu 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