A transepithelial pathway delivers succinate to macrophages, thus perpetuating their pro-inflammatory metabolic state.

Autor:	Fremder M; Department of Clinical Biochemistry and Pharmacology, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel., Kim SW; Department of Internal Medicine and Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea; Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea; Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul, Korea., Khamaysi A; Department of Clinical Biochemistry and Pharmacology, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel., Shimshilashvili L; Department of Clinical Biochemistry and Pharmacology, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel., Eini-Rider H; Department of Clinical Biochemistry and Pharmacology, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel., Park IS; Department of Internal Medicine and Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea; Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea., Hadad U; The Ilse Katz Institute for Nanoscale Science and Technology Ben-Gurion University of the Negev, Beer-Sheva, Israel., Cheon JH; Department of Internal Medicine and Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea; Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea; Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul, Korea. Electronic address: geniushee@yuhs.ac., Ohana E; Department of Clinical Biochemistry and Pharmacology, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel. Electronic address: ohanaeh@bgu.ac.il.
Jazyk:	angličtina
Zdroj:	Cell reports [Cell Rep] 2021 Aug 10; Vol. 36 (6), pp. 109521.
DOI:	10.1016/j.celrep.2021.109521
Abstrakt:	The gut metabolite composition determined by the microbiota has paramount impact on gastrointestinal physiology. However, the role that bacterial metabolites play in communicating with host cells during inflammatory diseases is poorly understood. Here, we aim to identify the microbiota-determined output of the pro-inflammatory metabolite, succinate, and to elucidate the pathways that control transepithelial succinate absorption and subsequent succinate delivery to macrophages. We show a significant increase of succinate uptake into pro-inflammatory macrophages, which is controlled by Na + -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. Competing Interests: Declaration of interests The patent application “Succinate-Binding Polypeptides and Use Thereof” (PCT/IL2018/051060) by E.O. is related to this work. (Copyright © 2021. Published by Elsevier Inc.)
Databáze:	MEDLINE
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