PROBIOTIC YEAST TREATMENT ATTENUATES IRINOTECAN INDUCED INTESTINAL MUCOSITIS IN MICE AND IN VITRO MODEL

GIRARDI JI; FERREYRA M; ERREA AJ; RUMBO M

Santiago de Chile

Otro; IUIS, SMI, ALAI, LAMIG, ASOCHIN INFLAMMATION, CANCER AND INTESTINAL MUCOSAL IMMUNOLOGY (ICIMI) ADVANCED IMMUNOLOGY COURSE 2023; 2023

International Union of Immunological Societies

Irinotecan is a chemotherapeutic drug commonly used in colorectal metastatic cancer therapy. It can generate intestinal cytotoxic damage, triggering a drug induced mucositis. Given its severity, it can force the interruption of the chemotherapeutic scheme with consequent impact on disease progression. For that, we aimed to evaluate an intervention using the probiotic yeast Kluyveromyces marxianus CIDCA 8154 (Km8154), whose anti-inflammatory and anti-oxidative capabilities and protective properties in intestinal colitis models have previously been reported. Effect of heat killed (HK) yeast administration was also evaluated.In-vitro studies: reporter CACO-2 cell line with luciferase gene under CCL20 promoter were treated with Irinotecan and supplemented with Km8154. After incubation, luciferase activity was measured to assess inflammatory response. In addition, cell oxidative stress was measured using H2-DCFDA probe by flow cytometry.In-vivo studies: Irinotecan 75mg/kg was administered to BALB/c mice to induce the drug associated mucositis and the Km8154 intervention group had the yeast administered daily by gavage at 10^9 UFC/ml until endpoint. Seven days after the first irinotecan dose, mice were killed, and intestinal samples were obtained. Clinical, histopathological and biochemical parameters were evaluated.In-vitro studies have shown that irinotecan treatment induce activation of reporter Caco-2 cells and Km8154 co-treatment is able to reduce the production of luciferase in irinotecan treated cells (p=0.0018). Km8154 co-treatment showed a mildy attenuation of irinotecan induced oxidative stress in cell line (p0.0519).In-vivo studies have shown that both yeast and HK treatment improved histopathological and diarrheal scored of mice treated with Irinotecan while protecting against intestinal damage measured with a villus/crypt ratio (p=0.0006) and intestinal shortening (p=0.0049). Furthermore, HK treatment also showed protection against irinotecan induced weight loss (p