Kume Miki, Din Jin, Zegarra-Ruiz Daniel F
Carter Immunology Center, University of Virginia, Charlottesville, VA 22908, USA.
Microorganisms. 2025 Mar 1;13(3):556. doi: 10.3390/microorganisms13030556.
Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by chronic inflammation that affects multiple organs, with its prevalence varying by ethnicity. Intestinal dysbiosis has been observed in both SLE patients and murine models. 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.
系统性红斑狼疮（SLE）是一种自身免疫性疾病，其特征为影响多个器官的慢性炎症，患病率因种族而异。在SLE患者和小鼠模型中均观察到肠道菌群失调。此外，肠道屏障受损被认为有助于致病共生菌逃避和突破免疫防御，导致抗原交叉反应、微生物易位、随后的免疫激活，并最终导致多器官衰竭。由于使用人类样本难以研究这些过程的详细机制，小鼠模型至关重要。各种SLE小鼠模型，包括基因改造的自发和诱导性小鼠模型，有助于深入了解致病共生菌及其如何失调全身免疫系统。此外，由于微生物代谢产物调节全身免疫反应，细菌及其代谢产物可作为治疗靶点。基于人类和小鼠研究的见解，本综述探讨了狼疮致病共生菌如何引发肠道和全身免疫失调。粪便微生物群移植和饮食调整等治疗方法显示出作为预防和治疗SLE的经济有效且安全方法的潜力。了解微生物群、宿主因素和免疫失调之间的复杂相互作用对于开发新的个性化疗法来应对这种多方面的疾病至关重要。
