Effect of lactate in a murine model of colitis

IRAPORDA C.; ROMANIN D.E., CAYET D., SIRARD J.C., ; GARROTE G L; ABRAHAM A.G.; RUMBO M.

Simposio; V Simposio Internacional de Bacterias Lácticas (SIBAL); 2016

CERELA- CONICET

We have previously shown that the non bacterial fraction of kefir milk can modulate inflammatory activation of intestinal epithelial cells and that lactate present in this fraction may be the principal component responsible of this property. In order to link the in vitro capacity of lactate to the in vivo effect, we evaluated the potential to protect mice from TNBS-induced colitis. 22-25g 6-weeks old Balb/c mice were employed. Lactate 200 mM was administered either orally or by intrarectal instillation (200 µl); control groups received water intake or an instillation of PBS. Experimental colitis was induced 5 days after oral intake or 2 h after instillations, by intrarectal administration of 0.5 mg of TNBS in 50% ethanol or 50% ethanol as control. Animals were sacrificed after 48h. With the aim of study the possible mechanism involved in the immunomodulatory activity the in vitro Caco-2 ccl20:luc cell reporter system was used. We evaluated the effect of preincubation of cells with different concentration of lactate and glycolysis inhibitors (such as 2-deoxyglucose, 3 bromo-priruvate or sodium oxamate) and analyzed the glucose intake, lactate production and luciferase activity induced by flagelin (Flic). In the in vivo TNBS-induced colitis model, no significant variation in weight and no signs of inflammation were observed in vehicle groups. Characteristic features of colitis, colonic inflammation with several epithelial damage were observed in PBS-treated group, leading to an inflammation score of 4.67 ±2.34, and higher concentration of serum IL-6 after 24 h (p