Indole-3-Propionic Acid, a Gut Microbiota Metabolite, Protects Against the Development of Postoperative Delirium
文献类型：期刊论文
| 作者 | Zhou, Xue12; Wu, Xinbo11,12; Wu, Yan10; Yang, Liuyue12; Shi, Eleanor9; Ding, Weihua12; Chen, Liang8; Shi, Xu7; Feng, Xia10; Su, Chienwen6 |
| 刊名 | ANNALS OF SURGERY
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| 出版日期 | 2023-12-01 |
| 卷号 | 278期号:6页码:E1164-E1174 |
| ISSN号 | 0003-4932 |
| 关键词 | gut microbiota indole-3-propionic acid anesthesia surgery postoperative delirium |
| DOI | 10.1097/SLA.0000000000005886 |
| 通讯作者 | Chen, Qian(qianchen@mit.edu) ; Xie, Zhongcong(zxie@mgh.harvard.edu) ; Shen, Shiqian(sshen2@mgh.harvard.edu) |
| 英文摘要 | Objective: The aim was to determine preoperative gut microbiota metabolites that may be associated with postoperative delirium (POD) development in patients and further study in rodents. Summary Background Data: POD occurs in 9% to 50% of older patients undergoing anesthesia/surgery but lacks effective treatments or prevention. High-throughput metabolomics using liquid chromatography with tandem mass spectrometry has accelerated disease-related biomarkers discovery. We performed metabolomic studies in humans to identify potential metabolite biomarkers linked to POD and examined potential mechanisms in rodents. Methods: We performed a prospective observational cohort study to examine the metabolomic changes that were associated with the development of POD. Then the gut microbiota-related metabolomic changes were recapitulated by gut microbiota perturbation in rodents. POD was assessed in mice using a battery of behavioral tests including novel objective test, Y-maze test, open-field test, and buried food test. The mechanisms through which gut microbiota-related metabolomic changes influenced POD were examined using chemogenetics. Results: Indole-3-propionic acid (IPA) is a gut microbiota metabolite that belongs to the indole family. Baseline plasma levels of IPA were significantly inversely correlated with the onset of POD in 103 (17 cases) human individuals. This relationship was validated in preclinical mouse models for POD: reducing IPA levels through gut microbiota perturbation promoted POD-like behavior. More importantly, IPA administration deterred POD-like behavior. Colonization of germ-free mice with mutant Clostridium sporogenes that did not produce IPA-promoted POD-like behavior. Chemogenetic studies revealed that the protective effect of IPA in mice was mediated, in part, by peroxisome proliferator-activated receptor gamma coactivator 1-alpha in hippocampal interneurons. Conclusions: Gut microbiota-derived IPA is an important molecule implicated in the pathogenesis of POD, which could potentially be harnessed for POD prevention. |
| WOS关键词 | RISK ; METABOLOMICS ; MECHANISMS ; NEUROINFLAMMATION ; NEURODEGENERATION ; CONTRIBUTES ; DREADDS ; BRAIN ; MICE |
| 资助项目 | NIH[NS116423] ; NIH[AG067947] ; NIH[AG065606] ; NIH[NS126029] |
| WOS研究方向 | Surgery |
| 语种 | 英语 |
| 出版者 | LIPPINCOTT WILLIAMS & WILKINS |
| WOS记录号 | WOS:001162552900005 |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/309877]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | Chen, Qian; Xie, Zhongcong; Shen, Shiqian |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Materia Med, Shanghai, Peoples R China 2.MIT, McGovern Inst Brain Res, Cambridge, MA 02139 USA 3.Harvard Med Sch, Massachusetts Gen Hosp, Dept Radiat Oncol, Steele Lab, Boston, MA USA 4.Brigham & Womens Hosp, Dept Pathol, Boston, MA USA 5.McGill Univ, Dept Parasitol, Montreal, PQ, Canada 6.Harvard Med Sch, Massachusetts Gen Hosp, Dept Pediat, Boston, MA USA 7.Beth Israel Deaconess Med Ctr, Dept Cardiovasc Med, Boston, MA USA 8.Hackensack Hlth Care, Ctr Discovery & Innovat, Hackensack, NJ USA 9.Harvard Med Sch, Dana Farber Canc Inst, Boston, MA USA 10.Sun Yat Sen Univ, Affiliated Hosp 1, Dept Anesthesiol, Guangzhou, Peoples R China |
| 推荐引用方式 GB/T 7714 | Zhou, Xue,Wu, Xinbo,Wu, Yan,et al. Indole-3-Propionic Acid, a Gut Microbiota Metabolite, Protects Against the Development of Postoperative Delirium[J]. ANNALS OF SURGERY,2023,278(6):E1164-E1174. |
| APA | Zhou, Xue.,Wu, Xinbo.,Wu, Yan.,Yang, Liuyue.,Shi, Eleanor.,...&Shen, Shiqian.(2023).Indole-3-Propionic Acid, a Gut Microbiota Metabolite, Protects Against the Development of Postoperative Delirium.ANNALS OF SURGERY,278(6),E1164-E1174. |
| MLA | Zhou, Xue,et al."Indole-3-Propionic Acid, a Gut Microbiota Metabolite, Protects Against the Development of Postoperative Delirium".ANNALS OF SURGERY 278.6(2023):E1164-E1174. |
入库方式： OAI收割
来源：上海药物研究所
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