Butyrate Prevents the Pathogenic Anemia‐Inflammation Circuit by Facilitating Macrophage Iron Export
Abstract: Most patients with inflammatory bowel disease (IBD) develop anemia, which is attributed to the dysregulation of iron metabolism. Reciprocally, impaired iron homeostasis also aggravates inflammation. How this iron‐mediated, pathogenic anemia‐inflammation crosstalk is regulated in the gut remains elusive. Herein, it is for the first time revealed that anemic IBD patients exhibit impaired production of short‐chain fatty acids (SCFAs), particularly butyrate. Butyrate supplementation restores iron metabolism in multiple anemia models. Mechanistically, butyrate upregulates ferroportin (FPN) expression in macrophages by reducing the enrichment of histone deacetylase (HDAC) at the Slc40a1 promoter, thereby facilitating iron export. By preventing iron sequestration, butyrate not only mitigates colitis‐induced anemia but also reduces TNF‐α production in macrophages. Consistently, macrophage‐conditional FPN knockout mice exhibit more severe anemia and inflammation. Finally, it is revealed that macrophage iron overload impairs the therapeutic effectiveness of anti‐TNF‐α antibodies in colitis, which can be reversed by butyrate supplementation. Hence, this study uncovers the pivotal role of butyrate in preventing the pathogenic circuit between anemia and inflammation.
- Location
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Deutsche Nationalbibliothek Frankfurt am Main
- Extent
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Online-Ressource
- Language
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Englisch
- Bibliographic citation
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Butyrate Prevents the Pathogenic Anemia‐Inflammation Circuit by Facilitating Macrophage Iron Export ; day:18 ; month:01 ; year:2024 ; extent:13
Advanced science ; (18.01.2024) (gesamt 13)
- Creator
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Xiao, Peng
Cai, Xuechun
Zhang, Zhou
Guo, Ke
Ke, Yuehai
Hu, Ziwei
Song, Zhangfa
Zhao, Yuening
Yao, Lingya
Shen, Manlu
Li, Jingyun
Huang, Youling
Ye, Lingna
Huang, Lingjie
Zhang, Yu
Liu, Rongbei
Xu, Mengque
Xu, Xutao
Zhao, Yuan
Cao, Qian
- DOI
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10.1002/advs.202306571
- URN
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urn:nbn:de:101:1-2024011814203245549217
- Rights
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Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
- Last update
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15.08.2025, 7:23 AM CEST
Data provider
Deutsche Nationalbibliothek. If you have any questions about the object, please contact the data provider.
Associated
- Xiao, Peng
- Cai, Xuechun
- Zhang, Zhou
- Guo, Ke
- Ke, Yuehai
- Hu, Ziwei
- Song, Zhangfa
- Zhao, Yuening
- Yao, Lingya
- Shen, Manlu
- Li, Jingyun
- Huang, Youling
- Ye, Lingna
- Huang, Lingjie
- Zhang, Yu
- Liu, Rongbei
- Xu, Mengque
- Xu, Xutao
- Zhao, Yuan
- Cao, Qian
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