Local treatment with lactate prevents intestinal inflammation in the TNBS-induced colitis model

IRAPORDA, CAROLINA; ROMANIN, DAVID E.; BENGOA, ANA AGUSTINA; ERREA, AGUSTINA J.; CAYET, DELPHINE; FOLIGNÉ, BENOIT; SIRARD, JEAN C.; GARROTE, GRACIELA LILIANA; ABRAHAM, ANALÍA GRACIELA; RUMBO, MARTIN

Frontiers in Immunology

Frontiers Media S. A.

Año: 2016 vol. 7

Lactate has long been considered as a metabolic by-product of cells. Recently, thisview has been changed by the observation that lactate can act as a signaling moleculeand regulates critical functions of the immune system. We previously identified lactateas the component responsible for the modulation of innate immune epithelial responseof fermented milk supernatants in vitro. We have also shown that lactate downregulatesproinflammatory responses of macrophages and dendritic cells. So far, in vivo effectsof lactate on intestinal inflammation have not been reported. We evaluated the effect ofintrarectal administration of lactate in a murine model of colitis induced by 2,4,6-trinitrobenzenesulfonicacid (TNBS). The increase in lactate concentration in colon promotedprotective effects against TNBS-induced colitis preventing histopathological damage, aswell as bacterial translocation and rise of IL-6 levels in serum. Using intestinal epithelialreporter cells, we found that flagellin treatment induced reporter gene expression, whichwas abrogated by lactate treatment as well as by glycolysis inhibitors. Furthermore,lactate treatment modulated glucose uptake, indicating that high levels of extracellularlactate can impair metabolic reprograming induced by proinflammatory activation. Theseresults suggest that lactate could be a potential beneficial microbiota metabolite andmay constitute an overlooked effector with modulatory properties.