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Libro de resumenes - Anti-inflammatory effects of Saccharomyces boulardii CNCM I-745 in a mouse model of proximal small intestine gluten-related disease.
Congreso
Autoría:
Miculan Emanuel ; Stefaneli C ; Iribarren ML ; Ducca Geronimo ; Lezcano A ; CHIRDO, FERNANDO GABRIELFecha:
2023Editorial y Lugar de Edición:
UEGResumen *
Introduction. Saccharomyces boulardii CNCM I-745 probiotic properties have been demonstrated for decades. The exact mechanisms behind these beneficial effects are widely documented, notably anti-inflammatory properties and preservation of the intestinal barrier integrity. However most of the current knowledge was obtained from studies focusing on infectious or inflammatory colonic diseases and very little is known regarding the effects of this yeast on small intestine pathologies.In previous work, we showed that after oral gavage of p31-43 gliadin peptide, a fragment of gluten-derived peptides that neither binds to HLA class II molecules nor induces T cell activation, is responsible for toxic effects and strong inflammatory responses in the proximal small intestine (Gomes Castro et al., 2019, Ruera C et al, 2020). In this mouse model, intragastric administration of p31-43 elicits mucosal damage in small intestinal together with the production of inflammatory mediators, inflammasome activation, and cell death. Aim. To study the effects of S. boulardii pre-treatment on the inflammatory response in the proximal small intestine in a mouse model of sterile inflammation induced by p31-43.Materials and Methods. Seven week-old C57BL/6 mice were housed under specific pathogen-free conditions and allowed access to autoclaved food and water ad libitum. A three-weeks pretreating phase by gavage with S. boulardii CNCM I-745 (3g/kg/day) or vehicle (Phosphate-buffered saline, PBS), was performed. Then, a single dose of 20µg of p31-43 gliadin peptide (LGQQQPFPPQQPY, at > 95% purity) per mouse or PBS, was delivered by intragastric administration. Mice were euthanized 4 or 16 hours after challenge and proximal small intestine was sampled to perform different histological analysis: villus high/crypt depth (V/C) ratio, intraepithelial lymphocytes (IELs) counting, cell death by TUNEL staining. Assessment of the activation of caspase-1, a central mediator of inflammasome pathway, was performed by Western Blot on small intestinal samples. Statistics were performed using Anova Test.Results. The evaluation of the histological changes at the proximal small intestine showed that administration of S. boulardii was able to prevent the damage induced by p31-43 for both 4h (p< 0.01) and 16h (<0.0003) after p31-43 treatment. This treatment also prevented mucosal IELs recruitment. The assessment of cell death by TUNEL staining on sections of the small intestine showed that S. boulardii was effective to block the induction of cell death caused by p31-43 (p< 0.005).Pretreatment with S boulardii before the p31-43 challenge reduced inflammasome activation by maintaining caspase-1 to basal levels (p<0.01).Conclusions. Three-week phase of preconditioning with S. boulardii before the p31-43 treatment prevented intestinal macroscopic damage, the increase in IELs numbers, cell death and inflammasome activation. These findings show the beneficial effects of S. boulardii CNCM I-745 in proximal small intestine inflammatory conditions and may be of interest in celiac disease patients. Información suministrada por el agente en SIGEVAPalabras Clave
celiac diseaseprobiotic