Dell'Atti Federica, Abreu Hugo, Malfa Patrizia, Raineri Davide, Cappellano Giuseppe, Chiocchetti Annalisa
Department of Health Sciences, Interdisciplinary Research Center of Autoimmune Diseases (IRCAD), Università del Piemonte Orientale, Novara, Italy.
Center for Translational Research on Autoimmune and Allergic Disease (CAAD), Università del Piemonte Orientale, Novara, Italy.
Front Immunol. 2025 Aug 7;16:1620185. doi: 10.3389/fimmu.2025.1620185. eCollection 2025.
Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by systemic inflammation and joint damage. Emerging evidence highlights the role of gut and oral microbiota in RA pathogenesis, with microbial dysbiosis potentially exacerbating inflammation and immune dysregulation. Although probiotics have shown potential in modulating the oral and gut microbiota and improving RA symptoms, a promising cell-free substitute is provided by postbiotics, including probiotic-derived extracellular vesicles (EVs). These bioactive nanoparticles transport functional metabolites capable of modulating immune responses, reducing inflammation, and restoring gut barrier integrity. Probiotic-derived EVs are, for instance, able to promote M2 macrophage polarization and suppress pro-inflammatory cytokines, thus highlighting their therapeutic potential. Nonetheless, challenges remain in standardizing EVs production, optimizing administration routes, and ensuring clinical safety. The targeting and effectiveness of probiotic EVs may be improved by developments in omics sciences and biotechnology techniques, making them the next breakthrough in postbiotics for the treatment of RA. This review examines how probiotic-derived EVs interact with the host, focusing on their crosstalk with immune cells and subsequent immune modulation. We highlight their potential for RA treatment, discuss clinical challenges, and explore their use in personalized medicine.
类风湿性关节炎(RA)是一种慢性自身免疫性疾病,其特征为全身性炎症和关节损伤。新出现的证据凸显了肠道和口腔微生物群在类风湿性关节炎发病机制中的作用,微生物失调可能会加剧炎症和免疫失调。尽管益生菌已显示出调节口腔和肠道微生物群以及改善类风湿性关节炎症状的潜力,但后生元提供了一种有前景的无细胞替代物,包括益生菌衍生的细胞外囊泡(EVs)。这些生物活性纳米颗粒运输能够调节免疫反应、减轻炎症和恢复肠道屏障完整性的功能性代谢物。例如,益生菌衍生的细胞外囊泡能够促进M2巨噬细胞极化并抑制促炎细胞因子,从而凸显了它们的治疗潜力。尽管如此,在细胞外囊泡生产标准化、优化给药途径和确保临床安全性方面仍存在挑战。组学科学和生物技术的发展可能会提高益生菌细胞外囊泡的靶向性和有效性,使其成为后生元治疗类风湿性关节炎的下一个突破。本综述探讨了益生菌衍生的细胞外囊泡如何与宿主相互作用,重点关注它们与免疫细胞的相互作用以及随后的免疫调节。我们强调它们在类风湿性关节炎治疗中的潜力,讨论临床挑战,并探索它们在个性化医疗中的应用。
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