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

Authors
 Moran Fremder  ;  Seung Won Kim  ;  Ahlam Khamaysi  ;  Liana Shimshilashvili  ;  Hadar Eini-Rider  ;  I Seul Park  ;  Uzi Hadad  ;  Jae Hee Cheon  ;  Ehud Ohana 
Citation
 CELL REPORTS, Vol.36(6) : 109521, 2021-08 
Journal Title
CELL REPORTS
Issue Date
2021-08
Keywords
citrate ; epithelia ; inflammation ; ion transport ; macrophages ; metabolism ; microbiota ; succinate
Abstract
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.
Files in This Item:
T202104845.pdf Download
DOI
10.1016/j.celrep.2021.109521
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Others (기타) > 1. Journal Papers
Yonsei Authors
Kim, Seung Won(김승원) ORCID logo https://orcid.org/0000-0002-1692-1192
Cheon, Jae Hee(천재희) ORCID logo https://orcid.org/0000-0002-2282-8904
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/186941
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