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Extracellular Vesicles from Probiotic and Beneficial Escherichia coli Strains Exert Multifaceted Protective Effects Against Rotavirus Infection in Intestinal Epithelial Cells
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Rotavirus remains a major cause of severe acute gastroenteritisin infants worldwide. The suboptimal efficacy of current vaccines underscores the needfor alternative microbiome-based interventions, including postbiotics. Extracellularvesicles (EVs) from probiotic and commensal E. coli strains have been shown to mitigatediarrhea and enhance immune responses in a suckling-rat model of rotavirus infection.Here, we investigate the regulatory mechanisms activated by EVs in rotavirus-infectedenterocytes. Methods: Polarized Caco-2 monolayers were used as a model of matureenterocytes. Cells were pre-incubated with EVs from the probiotic E. coli Nissle 1917 (EcN)or the commensal EcoR12 strain before rotavirus infection. Intracellular Ca2+concentration, ROS levels, and the expression of immune- and barrier-related genes andproteins were assessed at multiple time points post-infection. Results: EVs from bothstrains exerted broad protective effects against rotavirus-induced cellular dysregulation,with several responses being strain-specific. EVs interfered with viral replication bycounteracting host cellular processes essential for rotavirus propagation. Specifically, EVtreatment significantly reduced rotavirus-induced intracellular Ca2+ mobilization, ROSproduction, and COX-2 expression. In addition, both EV types reduced virus-inducedmucin secretion and preserved tight junction organization, thereby limiting viral accessto basolateral coreceptors. Additionally, EVs enhanced innate antiviral defenses viadistinct, strain-dependent pathways: EcN EVs amplified IL-8-mediated responses,whereas EcoR12 EVs preserved the expression of interferon-related signaling genes.Conclusions: EVs from EcN and EcoR12 act through multiple complementarymechanisms to restrict rotavirus replication, spread, and immune evasion. These findingssupport their potential as effective postbiotic candidates for preventing or treatingrotavirus infection.
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CORDERO, Cecilia, CABALLERO ROMAN, Aitor, MARTÍNEZ-RUIZ, Sergio, OLIVO-MARTINEZ, Yenifer, BALDOMÀ LLAVINÉS, Laura, BADÍA PALACÍN, Josefa. Extracellular Vesicles from Probiotic and Beneficial Escherichia coli Strains Exert Multifaceted Protective Effects Against Rotavirus Infection in Intestinal Epithelial Cells. _Pharmaceutics_. 2026. Vol. 18, núm. 1. [consulta: 25 de gener de 2026]. ISSN: 1999-4923. [Disponible a: https://hdl.handle.net/2445/225945]