Anti-inflammatory effects of Saccharomyces boulardii CNCM I-745 in a mouse model of proximal small intestine gluten-related disease

MICULÁN, EMANUEL; STEFANELLI CAMILA; IRIBARREN MARÍA LUZ; DUCCA, GERÓNIMO; LEZCANO ALUMINE; PEREZ TOLOSA GISELA; CAROLINA N. RUERA; CHIRDO FERNANDO

Copenhagen, Denmark

Congreso; UEGweek 2023 (United European Gastroenterology); 2023

United European Gastroenterology

ANTI-INFLAMMATORY EFFECTS OF SACCHAROMYCES BOULARDII CNCM I-745 IN A MOUSE MODEL OF PROXIMAL SMALL INTESTINE GLUTEN-RELATED DISEASEE. Miculan1, C. Stefanelli1 , M.L. Iribarren1 , G. Ducca1 , A. Lezcano1,G. Perez Tolosa1, C. Ruera1, F. Chirdo11Instituto de Estudios Inmunologicos y Fisiopatologicos ( IIFP) (UNLP-CONICET), Facultad de Ciencias Exactas. Universidad Nacional de La Plata, La Plata, ArgentinaContact E-Mail Address: fchirdo@gmail.comIntroduction: 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. Howevermost 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.Aims & Methods: 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-bufferedsaline, 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, intraepitheliallymphocytes (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 (