2. Academic Validation
  3. Bifidobacterium longum Metabolite Indole-3-Carboxaldehyde Blocks HDAC3 and Inhibits Macrophage NLRP3 Inflammasome Activation in Intestinal Ischemia/Reperfusion Injury

Bifidobacterium longum Metabolite Indole-3-Carboxaldehyde Blocks HDAC3 and Inhibits Macrophage NLRP3 Inflammasome Activation in Intestinal Ischemia/Reperfusion Injury

  • Inflammation. 2024 Dec 11. doi: 10.1007/s10753-024-02211-2.
Yan Miao 1 2,  Mian Wang 1 2,  Hao Sun 1 2,  Yujie Zhang 3,  Wei Zhou 1 2,  Wanli Yang 1 2,  Lili Duan 1 2,  Liaoran Niu 1 2,  Zhenshun Li 1 2,  Junfeng Chen 1 2,  Yiding Li 1 2,  Aqiang Fan 1 2,  Qibin Xie 1 2,  Siyu Wei 1 2,  Han Bai 1 2,  Chenyang Wang 1 2,  Qian Chen 1 2,  Xiangjie Wang 1 2,  Yunlong Li 1 2,  Jinqiang Liu 1 2,  Yu Han 4,  Daiming Fan 2,  Liu Hong 5 6
Affiliations

Affiliations

  • 1 Department of Digestive Surgery, Xijing Hospital of Digestive Diseases, Air Force Medical University, No. 127, Changle West Road, Xi'an, 710032, Shaanxi, P.R. China.
  • 2 State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers and National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive Diseases, Air Force Medical University, Xi'an, 710032, Shaanxi, P.R. China.
  • 3 Department of Histology and Embryology, School of Basic Medicine, Xi'an Medical University, Xi'an, 710032, Shaanxi, P.R. China.
  • 4 Department of Otolaryngology, Xijing Hospital, Air Force Medical University, Xi'an, 710032, Shaanxi, P.R. China.
  • 5 Department of Digestive Surgery, Xijing Hospital of Digestive Diseases, Air Force Medical University, No. 127, Changle West Road, Xi'an, 710032, Shaanxi, P.R. China. hongliufmmu@163.com.
  • 6 State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers and National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive Diseases, Air Force Medical University, Xi'an, 710032, Shaanxi, P.R. China. hongliufmmu@163.com.
PMID: 39663332 DOI: 10.1007/s10753-024-02211-2
Abstract

Indole-3-carboxaldehyde (3-IAld), a tryptophan metabolite derived from gut microbiota, has been reported to protect the intestine against radiation injury. This study aimed to clarify the role of Bifidobacterium longum (B. longum) and its metabolite indole-3-carboxaldehyde (3-IAld) in the pathophysiology of intestinal ischemia/reperfusion (II/R) injury. Superior mesenteric artery occlusion and reperfusion were performed to establish II/R mice, and pathological injury in II/R mice was evaluated. II/R mice showed impaired gut microbiota diversity and reduced abundance of B. longum in the intestines. Transplantation of B. longum mitigated II/R injury by protecting the integrity of the intestinal barrier and reducing inflammatory response. The 3-IAld level increased after transplantation of B. longum, and 3-IAld treatment inhibited the inflammatory response of bone marrow-derived macrophages (BMDM). Histone deacetylase 3 (HDAC3) was a target of 3-IAld, and HDAC3 was translocated to mitochondria to promote mitochondrial fatty acid oxidation (FAO) during macrophage inflammasome formation. HDAC3 overexpression promoted the formation of macrophage inflammasomes in intestinal tissues. Overall, this study confirmed the beneficial effects of B. longum in combating II/R injury through HDAC3-mediated control of mitochondrial FAO and macrophage inflammasome formation via 3-IAld.

Keywords

Bifidobacterium longum; 3-carboxaldehyde; HDAC3; Intestinal ischemia/reperfusion; Mitochondrial fatty acid oxidation.

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