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Additionally, intestinal barrier impairment is thought to contribute to the ability of pathobionts to evade and breach immune defenses, resulting in antigen cross-reactivity, microbial translocation, subsequent immune activation, and, ultimately, multiple organ failure. Since the detailed mechanisms underlying these processes are difficult to examine using human samples, murine models are crucial. Various SLE murine models, including genetically modified spontaneous and inducible murine models, offer insights into pathobionts and how they dysregulate systemic immune systems. Furthermore, since microbial metabolites modulate systemic immune responses, bacteria and their metabolites can be targeted for treatment. Based on human and mouse research insights, this review examines how lupus pathobionts trigger intestinal and systemic immune dysregulation. Therapeutic approaches, such as fecal microbiota transplantation and dietary adjustments, show potential as cost-effective and safe methods for preventing and treating SLE. Understanding the complex interactions between the microbiota, host factors, and immune dysregulation is essential for developing novel, personalized therapies to tackle this multifaceted disease.<\/jats:p>","DOI":"10.3390\/microorganisms13030556","type":"journal-article","created":{"date-parts":[[2025,3,3]],"date-time":"2025-03-03T09:04:49Z","timestamp":1740992689000},"page":"556","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Dysregulated Intestinal Host\u2013Microbe Interactions in Systemic Lupus Erythematosus: Insights from Patients and Mouse Models"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7632-6072","authenticated-orcid":false,"given":"Miki","family":"Kume","sequence":"first","affiliation":[{"name":"Carter Immunology Center, University of Virginia, Charlottesville, VA 22908, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin","family":"Din","sequence":"additional","affiliation":[{"name":"Carter Immunology Center, University of Virginia, Charlottesville, VA 22908, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0752-7238","authenticated-orcid":false,"given":"Daniel F.","family":"Zegarra-Ruiz","sequence":"additional","affiliation":[{"name":"Carter Immunology Center, University of Virginia, Charlottesville, VA 22908, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,3,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1038\/s41577-022-00727-y","article-title":"The Impact of the Gut Microbiome on Extra-Intestinal Autoimmune Diseases","volume":"23","author":"Miyauchi","year":"2023","journal-title":"Nat. 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