Extracellular vesicles from microbiota-derived Escherichia coli strains as a postbiotic strategy to Enhance intestinal maturation and modulate gut-liver and gut-brain communication axes
[eng] The intestinal microbiota plays a crucial role in maintaining mucosal and systemic homeostasis, particularly during early life when the immune and epithelial systems are still developing. Among microbial-derived components, extracellular vesicles (EVs) produced by beneficial gut bacteria have...
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| Tipo de recurso: | tesis doctoral |
| Estado: | Versión publicada |
| Fecha de publicación: | 2025 |
| País: | España |
| Institución: | Universidad de Barcelona |
| Repositorio: | Dipòsit Digital de la UB |
| OAI Identifier: | oai:dnet:ubarcelona__::f94da392c5ebf2d536d212c107882849 |
| Acceso en línea: | https://hdl.handle.net/2445/229013 https://hdl.handle.net/10803/697254 |
| Access Level: | acceso embargado |
| Palabra clave: | Microbiota intestinal Malalties intestinals Immunologia Escheríchia coli Gastrointestinal microbiome Intestinal diseases Immunology Escherichia coli |
| Sumario: | [eng] The intestinal microbiota plays a crucial role in maintaining mucosal and systemic homeostasis, particularly during early life when the immune and epithelial systems are still developing. Among microbial-derived components, extracellular vesicles (EVs) produced by beneficial gut bacteria have emerged as promising postbiotic agents capable of modulating host physiology beyond the gut. This thesis investigates the immunomodulatory, antiviral, metabolic, and neurodevelopmental effects of EVs derived from Escherichia coli strains EcN (probiotic) and EcoR12 (commensal) in in vivo neonatal and in vitro models. In healthy neonatal rats, oral administration of E. coli EVs enhanced humoral and cellular immune responses, promoted intestinal epithelial maturation, and accelerated the development of a balanced Th1/Th2 immune profile without inducing inflammation. In a neonatal rotavirus infection model, EV treatment reduced diarrhea severity, preserved mucosal integrity, and stimulated virus-specific immunity. These protective effects were linked to the modulation of serotonin-related pathways and mucin secretion. Beyond the gut, administered EVs reached the liver and induced gene expression profiles favoring anti-inflammatory, antioxidant, and lipid oxidation pathways, supporting their role in gut–liver axis communication under physiological conditions. In In vitro cellular models derived from human inducible pluripotent steam cells (iPSC), EVs upregulated the expression of tight junction proteins in intestinal organoids and enhanced dendritic branching during neuronal differentiation. These findings suggested that microbiota EVs may have a dual action along the gut–brain axis, modulating intestinal epithelial barrier integrity and neurodevelopment. Collectively, the findings presented in this thesis position EcN- and EcoR12-derived EVs as safe and effective postbiotic candidates capable of supporting early-life immune and epithelial maturation, enhancing antiviral defenses, and modulating organ functions across diverse gut-organ axis. Moreover, they provide a strong rationale for further investigation of microbiota-derived EVs in disease-relevant models and future translational studies. |
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