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

IRAPORDA CAROLINA; ERREA AGUSTINA; SIRARD JEAN CLAUDE; RUMBO MARTIN; ROMANIN DAVID E.; CAYET DELPHINE; GARROTE GRACIELA L.; BENGOA ANA A.; FOLIGNÉ BENOÎT ; ABRAHAM ANALÍA G.

Frontiers in Immunology

Frontiers

Año: 2016 vol. 7 p. 1 - 9

Lactate has long been considered as a metabolic by-product of cells. Recently, this view has been changed by the observation that lactate can act as a signaling molecule and regulates critical functions of the immune system. We previously identifed lactate as the component responsible for the modulation of innate immune epithelial response of fermented milk supernatants in vitro. We have also shown that lactate downregulates proinfammatory responses of macrophages and dendritic cells. So far, in  vivo effects of lactate on intestinal infammation have not been reported. We evaluated the effect of intrarectal administration of lactate in a murine model of colitis induced by 2,4,6-trinitro- benzenesulfonic acid (TNBS). The increase in lactate concentration in colon promoted protective effects against TNBS-induced colitis preventing histopathological damage, as well as bacterial translocation and rise of IL-6 levels in serum. Using intestinal epithelial reporter cells, we found that fagellin treatment induced reporter gene expression, which was abrogated by lactate treatment as well as by glycolysis inhibitors. Furthermore, lactate treatment modulated glucose uptake, indicating that high levels of extracellular lactate can impair metabolic reprograming induced by proinfammatory activation. These results suggest that lactate could be a potential benefcial microbiota metabolite and may constitute an overlooked effector with modulatory properties