4.7 Article

The gut microbiota metabolite capsiate promotes Gpx4 expression by activating TRPV1 to inhibit intestinal ischemia reperfusion-induced ferroptosis

期刊

GUT MICROBES
卷 13, 期 1, 页码 -

出版社

TAYLOR & FRANCIS INC
DOI: 10.1080/19490976.2021.1902719

关键词

Intestinal ischemia; reperfusion injury; metabolites; capsiate; ferroptosis; Gpx4; TRPV1

资金

  1. National Natural Science Foundation, Beijing, China [81671955, 82902010]
  2. Key Program of National Natural Science Foundation, Beijing, China [81730058]
  3. National Natural Science Foundation of China [81671955, 82902010, 81730058]

向作者/读者索取更多资源

Intestinal ischemia/reperfusion (I/R) injury disrupts gut microbiota and causes significant changes in metabolites, while capsiate (CAT), a gut microbiota metabolite, can alleviate ferroptosis-dependent intestinal I/R injury.
Ferroptosis, a new type of cell death has been found to aggravate intestinal ischemia/reperfusion (I/R) injury. However, little is known about the changes of gut microbiota and metabolites in intestinal I/R and the role of gut microbiota metabolites on ferroptosis-induced intestinal I/R injury. This study aimed to establish a mouse intestinal I/R model and ileum organoid hypoxia/reoxygenation (H/R) model to explore the changes of the gut microbiota and metabolites during intestinal I/R and protective ability of capsiate (CAT) against ferroptosis-dependent intestinal I/R injury. Intestinal I/R induced disturbance of gut microbiota and significant changes in metabolites. We found that CAT is a metabolite of the gut microbiota and that CAT levels in the preoperative stool of patients undergoing cardiopulmonary bypass were negatively correlated with intestinal I/R injury. Furthermore, CAT reduced ferroptosis-dependent intestinal I/R injury in vivo and in vitro. However, the protective effects of CAT against ferroptosis-dependent intestinal I/R injury were abolished by RSL3, an inhibitor of glutathione peroxidase 4 (Gpx4), which is a negative regulator of ferroptosis. We also found that the ability of CAT to promote Gpx4 expression and inhibit ferroptosis-dependent intestinal I/R injury was abrogated by JNJ-17203212, an antagonist of transient receptor potential cation channel subfamily V member 1 (TRPV1). This study suggests that the gut microbiota metabolite CAT enhances Gpx4 expression and inhibits ferroptosis by activating TRPV1 in intestinal I/R injury, providing a potential avenue for the management of intestinal I/R injury.

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