A transepithelial pathway delivers succinate to macrophages, thus perpetuating their pro-inflammatory metabolic state
Moran Fremder, Seung Won Kim, Ahlam Khamaysi, Liana Shimshilashvili, Hadar Eini-Rider, I Seul Park, Uzi Hadad, Jae Hee Cheon, Ehud Ohana
Abstract
-dependent succinate transporters in macrophages and epithelial cells. Furthermore, we find that fecal and serum succinate concentrations were markedly augmented in inflammatory bowel diseases (IBDs) and corresponded to changes in succinate-metabolizing gut bacteria. Together, our results describe a succinate production and transport pathway that controls the absorption of succinate generated by distinct gut bacteria and its delivery into macrophages. In IBD, this mechanism fails to protect against the succinate surge, which may result in chronic inflammation.
Topics & Concepts
MetaboliteInflammationGut floraMicrobiologyChemistryBacteriaInflammatory bowel diseaseMetabolismBiochemistryBiologyCell biologyImmunologyMedicineInternal medicineDiseaseGeneticsGut microbiota and healthImmune cells in cancerTryptophan and brain disorders