Probiotic-derived extracellular vesicles: the next breakthrough in postbiotics for rheumatoid arthritis

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 pr...

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Main Authors: Federica Dell’Atti, Hugo Abreu, Patrizia Malfa, Davide Raineri, Giuseppe Cappellano, Annalisa Chiocchetti
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-08-01
Series:Frontiers in Immunology
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Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2025.1620185/full
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author Federica Dell’Atti
Federica Dell’Atti
Hugo Abreu
Hugo Abreu
Patrizia Malfa
Davide Raineri
Davide Raineri
Giuseppe Cappellano
Giuseppe Cappellano
Annalisa Chiocchetti
Annalisa Chiocchetti
author_facet Federica Dell’Atti
Federica Dell’Atti
Hugo Abreu
Hugo Abreu
Patrizia Malfa
Davide Raineri
Davide Raineri
Giuseppe Cappellano
Giuseppe Cappellano
Annalisa Chiocchetti
Annalisa Chiocchetti
author_sort Federica Dell’Atti
collection DOAJ
description 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.
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publisher Frontiers Media S.A.
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spelling doaj-art-cfdb91c43bc44ad9a8a698dfc8fd1f402025-08-20T03:45:12ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-08-011610.3389/fimmu.2025.16201851620185Probiotic-derived extracellular vesicles: the next breakthrough in postbiotics for rheumatoid arthritisFederica Dell’Atti0Federica Dell’Atti1Hugo Abreu2Hugo Abreu3Patrizia Malfa4Davide Raineri5Davide Raineri6Giuseppe Cappellano7Giuseppe Cappellano8Annalisa Chiocchetti9Annalisa Chiocchetti10Department of Health Sciences, Interdisciplinary Research Center of Autoimmune Diseases (IRCAD), Università del Piemonte Orientale, Novara, ItalyCenter for Translational Research on Autoimmune and Allergic Disease (CAAD), Università del Piemonte Orientale, Novara, ItalyDepartment of Health Sciences, Interdisciplinary Research Center of Autoimmune Diseases (IRCAD), Università del Piemonte Orientale, Novara, ItalyCenter for Translational Research on Autoimmune and Allergic Disease (CAAD), Università del Piemonte Orientale, Novara, ItalyR&D Department, SynBalance Srl, Origgio, VA, ItalyDepartment of Health Sciences, Interdisciplinary Research Center of Autoimmune Diseases (IRCAD), Università del Piemonte Orientale, Novara, ItalyCenter for Translational Research on Autoimmune and Allergic Disease (CAAD), Università del Piemonte Orientale, Novara, ItalyDepartment of Health Sciences, Interdisciplinary Research Center of Autoimmune Diseases (IRCAD), Università del Piemonte Orientale, Novara, ItalyCenter for Translational Research on Autoimmune and Allergic Disease (CAAD), Università del Piemonte Orientale, Novara, ItalyDepartment of Health Sciences, Interdisciplinary Research Center of Autoimmune Diseases (IRCAD), Università del Piemonte Orientale, Novara, ItalyCenter for Translational Research on Autoimmune and Allergic Disease (CAAD), Università del Piemonte Orientale, Novara, ItalyRheumatoid 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.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1620185/fullextracellular vesiclesprobioticsdysbiosisinflammationarthritisimmunomodulation
spellingShingle Federica Dell’Atti
Federica Dell’Atti
Hugo Abreu
Hugo Abreu
Patrizia Malfa
Davide Raineri
Davide Raineri
Giuseppe Cappellano
Giuseppe Cappellano
Annalisa Chiocchetti
Annalisa Chiocchetti
Probiotic-derived extracellular vesicles: the next breakthrough in postbiotics for rheumatoid arthritis
Frontiers in Immunology
extracellular vesicles
probiotics
dysbiosis
inflammation
arthritis
immunomodulation
title Probiotic-derived extracellular vesicles: the next breakthrough in postbiotics for rheumatoid arthritis
title_full Probiotic-derived extracellular vesicles: the next breakthrough in postbiotics for rheumatoid arthritis
title_fullStr Probiotic-derived extracellular vesicles: the next breakthrough in postbiotics for rheumatoid arthritis
title_full_unstemmed Probiotic-derived extracellular vesicles: the next breakthrough in postbiotics for rheumatoid arthritis
title_short Probiotic-derived extracellular vesicles: the next breakthrough in postbiotics for rheumatoid arthritis
title_sort probiotic derived extracellular vesicles the next breakthrough in postbiotics for rheumatoid arthritis
topic extracellular vesicles
probiotics
dysbiosis
inflammation
arthritis
immunomodulation
url https://www.frontiersin.org/articles/10.3389/fimmu.2025.1620185/full
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