title: Local Treatment with Lactate Prevents Intestinal Inflammation in the TNBS-Induced Colitis Model.
abstract: 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 identified lactate as the component responsible for the modulation of innate immune epithelial response of fermented milk supernatantsin vitro. We have also shown that lactate downregulates proinflammatory responses of macrophages and dendritic cells. So far,in vivoeffects of lactate on intestinal inflammation have not been reported. We evaluated the effect of intrarectal administration of lactate in a murine model of colitis induced by 2,4,6-trinitrobenzenesulfonic 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 flagellin 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 proinflammatory activation. These results suggest that lactate could be a potential beneficial microbiota metabolite and may constitute an overlooked effector with modulatory properties.
authors.affiliation: Centro de Investigación y Desarrollo en Criotecnología de Alimentos (CIDCA, UNLP-CONICET-CIC.PBA) , La Plata , Argentina.
authors.forename: Carolina
authors.initials: C
authors.lastname: Iraporda
authors.affiliation: Instituto de Estudios Inmunológicos y Fisopatológicos (IIFP, UNLP-CONICET) , La Plata , Argentina.
authors.forename: David E
authors.initials: DE
authors.lastname: Romanin
authors.affiliation: Centro de Investigación y Desarrollo en Criotecnología de Alimentos (CIDCA, UNLP-CONICET-CIC.PBA) , La Plata , Argentina.
authors.forename: Ana A
authors.initials: AA
authors.lastname: Bengoa
authors.affiliation: Instituto de Estudios Inmunológicos y Fisopatológicos (IIFP, UNLP-CONICET) , La Plata , Argentina.
authors.forename: Agustina J
authors.initials: AJ
authors.lastname: Errea
authors.affiliation: CNRS, INSERM, CHU Lille, Institut Pasteur de Lille, U1019 - UMR 8204 - CIIL - Center for Infection and Immunity of Lille, University of Lille , Lille , France.
authors.forename: Delphine
authors.initials: D
authors.lastname: Cayet
authors.affiliation: CNRS, INSERM, CHU Lille, Institut Pasteur de Lille, U1019 - UMR 8204 - CIIL - Center for Infection and Immunity of Lille, University of Lille , Lille , France.
authors.forename: Benoit
authors.initials: B
authors.lastname: Foligné
authors.affiliation: CNRS, INSERM, CHU Lille, Institut Pasteur de Lille, U1019 - UMR 8204 - CIIL - Center for Infection and Immunity of Lille, University of Lille , Lille , France.
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Sirard
authors.affiliation: Centro de Investigación y Desarrollo en Criotecnología de Alimentos (CIDCA, UNLP-CONICET-CIC.PBA) , La Plata , Argentina.
authors.forename: Graciela L
authors.initials: GL
authors.lastname: Garrote
authors.affiliation: Centro de Investigación y Desarrollo en Criotecnología de Alimentos (CIDCA, UNLP-CONICET-CIC.PBA), La Plata, Argentina; Área Bioquímica y Control de Alimentos, Facultad de Ciencias Exactas, UNLP, La Plata, Argentina.
authors.forename: Analía G
authors.initials: AG
authors.lastname: Abraham
authors.affiliation: Instituto de Estudios Inmunológicos y Fisopatológicos (IIFP, UNLP-CONICET) , La Plata , Argentina.
authors.forename: Martín
authors.initials: M
authors.lastname: Rumbo
keywords: TNBS-induced colitis; flagellin; immunomodulation; innate immunity; lactate