{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T06:38:35Z","timestamp":1777012715103,"version":"3.51.4"},"reference-count":136,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T00:00:00Z","timestamp":1776988800000},"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>Systemic lupus erythematosus (SLE) is a prototypical autoimmune disease in which host-microbiota crosstalk plays a pivotal role in immune dysregulation. Recent metagenomic studies have revealed that disease-specific dysbiosis\u2014\u2014characterized by the expansion of pathobionts and depletion of immunoregulatory commensals\u2014\u2014occurs across the gut, oral cavity, skin, and genital tract. Integrative multi-omics analyses have identified three mechanistic pathways linking microbial imbalance to autoimmunity: (1) microbial peptides trigger molecular mimicry and epitope spreading, activating autoreactive lymphocytes: (2) microbial metabolites disrupt redox homeostasis, impair epithelial barriers, and skew the AhR-mediated Th17\/Treg balance; and (3) dysbiosis alters epigenetic regulation by inhibiting DNA methyltransferases, leading to hypomethylation of SLE-risk genes. Translational studies have shown that microbiome-targeted interventions, including probiotics, prebiotics, fecal microbiota transplantation, and even B cell-depleting chimeric antigen receptor T-cell (CAR-T) therapy, can restore microbial balance, reduce autoantibody levels, and modulate the gut-immune axis. Furthermore, microbial signatures are emerging as potential biomarkers for disease activity and treatment response. Despite this promise, challenges remain, such as the impact of immunosuppressants on the microbiota, spatial heterogeneity in host-microbe interactions, and limitations in causal inference. Looking forward, integrating single-cell metagenomics, microbiota-directed diets, and engineered microbial consortia may pave the way for personalized microbiome-based therapies. Reframing SLE as a \u201cmeta-organismal imbalance\u201d positions microbial ecology at the forefront of precision medicine.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1782828","type":"journal-article","created":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T05:43:34Z","timestamp":1777009414000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["The microbiota-systemic lupus erythematosus axis: mechanisms, diagnostics, and therapeutic frontiers"],"prefix":"10.3389","volume":"17","author":[{"given":"Miaomiao","family":"Hua","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine, The Fuyang Affiliated Hospital of Anhui Medical University","place":["Fuyang, Anhui, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jun","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, The Fuyang Affiliated Hospital of Anhui Medical 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