{"title":"索他利嗪通过肠-心-脑轴减轻心肌梗死小鼠的心脏功能障碍和抑郁样行为","authors":"","doi":"10.1016/j.nbd.2024.106598","DOIUrl":null,"url":null,"abstract":"<div><p>Myocardial infarction (MI) and depression are leading causes of mortality and morbidity globally, and these conditions are increasing recognized as being fundamentally interconnected. The recently recognized gut-heart-brain axis offers insights into depression following MI, but effective treatments for this comorbidity remain lacking. To address this medical need, we employed an animal model of MI to investigate the potential repurposing of sotagliflozin (SOTA), an approved sodium-glucose cotransporter 1 and 2 (SGLT1/2) inhibitor for diabetes, for managing depression following MI and identifying potential SOTA-associated microbial mechanisms. SOTA treatment improved cardiac dysfunction and alleviated depression-like behaviors induced by MI, accompanied by alterations in gut microbiota composition, such as changes in the <em>Prevotellaceae NK3B31 group</em>, <em>Alloprevotella</em>, and <em>Prevotellaceae UCG-001</em>. Moreover, fecal microbiota transplantation (FMT) using fecal samples from SOTA-treated MI mice demonstrated that gut microbiota contributed to the beneficial effects of SOTA on cardiac dysfunction and depression-like behaviors in MI mice. Intriguingly, FMT-based intervention and concordance analysis of gut microbiota before and after FMT suggested that <em>Prevotellaceae NK3B31 group</em>, <em>Alloprevotella</em>, and <em>Prevotellaceae UCG-001</em> were associated with the beneficial effects of SOTA. Furthermore, functional prediction of gut microbiota and correlation analysis support the significance of these dynamic microbial communities. In conclusion, these findings suggest that SOTA could serve as a potential drug to ameliorate cardiac dysfunction and depressive symptoms in MI patients via through the gut-heart-brain axis.</p></div>","PeriodicalId":19097,"journal":{"name":"Neurobiology of Disease","volume":null,"pages":null},"PeriodicalIF":5.1000,"publicationDate":"2024-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0969996124001980/pdfft?md5=b880ca0714e6dcd62b44e497472b4f33&pid=1-s2.0-S0969996124001980-main.pdf","citationCount":"0","resultStr":"{\"title\":\"Sotagliflozin attenuates cardiac dysfunction and depression-like behaviors in mice with myocardial infarction through the gut-heart-brain axis\",\"authors\":\"\",\"doi\":\"10.1016/j.nbd.2024.106598\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>Myocardial infarction (MI) and depression are leading causes of mortality and morbidity globally, and these conditions are increasing recognized as being fundamentally interconnected. The recently recognized gut-heart-brain axis offers insights into depression following MI, but effective treatments for this comorbidity remain lacking. To address this medical need, we employed an animal model of MI to investigate the potential repurposing of sotagliflozin (SOTA), an approved sodium-glucose cotransporter 1 and 2 (SGLT1/2) inhibitor for diabetes, for managing depression following MI and identifying potential SOTA-associated microbial mechanisms. SOTA treatment improved cardiac dysfunction and alleviated depression-like behaviors induced by MI, accompanied by alterations in gut microbiota composition, such as changes in the <em>Prevotellaceae NK3B31 group</em>, <em>Alloprevotella</em>, and <em>Prevotellaceae UCG-001</em>. Moreover, fecal microbiota transplantation (FMT) using fecal samples from SOTA-treated MI mice demonstrated that gut microbiota contributed to the beneficial effects of SOTA on cardiac dysfunction and depression-like behaviors in MI mice. Intriguingly, FMT-based intervention and concordance analysis of gut microbiota before and after FMT suggested that <em>Prevotellaceae NK3B31 group</em>, <em>Alloprevotella</em>, and <em>Prevotellaceae UCG-001</em> were associated with the beneficial effects of SOTA. Furthermore, functional prediction of gut microbiota and correlation analysis support the significance of these dynamic microbial communities. In conclusion, these findings suggest that SOTA could serve as a potential drug to ameliorate cardiac dysfunction and depressive symptoms in MI patients via through the gut-heart-brain axis.</p></div>\",\"PeriodicalId\":19097,\"journal\":{\"name\":\"Neurobiology of Disease\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":5.1000,\"publicationDate\":\"2024-07-11\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.sciencedirect.com/science/article/pii/S0969996124001980/pdfft?md5=b880ca0714e6dcd62b44e497472b4f33&pid=1-s2.0-S0969996124001980-main.pdf\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Neurobiology of Disease\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0969996124001980\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"NEUROSCIENCES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Neurobiology of Disease","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0969996124001980","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"NEUROSCIENCES","Score":null,"Total":0}
引用次数: 0
摘要
心肌梗死(MI)和抑郁症是导致全球死亡和发病的主要原因,而且这两种疾病越来越被认为是相互关联的。最近公认的肠-心-脑轴为心肌梗死后的抑郁提供了启示,但对这种并发症仍然缺乏有效的治疗方法。为了满足这一医疗需求,我们采用了一种心肌梗死动物模型来研究索他利氟嗪(SOTA)(一种已获批准的糖尿病钠-葡萄糖共转运体 1 和 2(SGLT1/2)抑制剂)在治疗心肌梗死后抑郁方面的潜在再利用可能性,并确定潜在的 SOTA 相关微生物机制。SOTA 治疗改善了心功能障碍,减轻了心肌梗死诱发的抑郁样行为,同时改变了肠道微生物群的组成,如前胡科 NK3B31 群、Alloprevotella 和前胡科 UCG-001 的变化。此外,利用经 SOTA 处理的 MI 小鼠的粪便样本进行粪便微生物群移植(FMT)证明,肠道微生物群有助于 SOTA 对 MI 小鼠的心脏功能障碍和抑郁样行为产生有益影响。耐人寻味的是,基于 FMT 的干预和 FMT 前后肠道微生物群的一致性分析表明,Prevotellaceae NK3B31 组、Alloprevotella 和 Prevotellaceae UCG-001 与 SOTA 的有益作用相关。此外,肠道微生物群的功能预测和相关性分析也支持这些动态微生物群落的重要性。总之,这些研究结果表明,SOTA 可作为一种潜在的药物,通过肠道-心脑轴改善心肌梗死患者的心功能障碍和抑郁症状。
Sotagliflozin attenuates cardiac dysfunction and depression-like behaviors in mice with myocardial infarction through the gut-heart-brain axis
Myocardial infarction (MI) and depression are leading causes of mortality and morbidity globally, and these conditions are increasing recognized as being fundamentally interconnected. The recently recognized gut-heart-brain axis offers insights into depression following MI, but effective treatments for this comorbidity remain lacking. To address this medical need, we employed an animal model of MI to investigate the potential repurposing of sotagliflozin (SOTA), an approved sodium-glucose cotransporter 1 and 2 (SGLT1/2) inhibitor for diabetes, for managing depression following MI and identifying potential SOTA-associated microbial mechanisms. SOTA treatment improved cardiac dysfunction and alleviated depression-like behaviors induced by MI, accompanied by alterations in gut microbiota composition, such as changes in the Prevotellaceae NK3B31 group, Alloprevotella, and Prevotellaceae UCG-001. Moreover, fecal microbiota transplantation (FMT) using fecal samples from SOTA-treated MI mice demonstrated that gut microbiota contributed to the beneficial effects of SOTA on cardiac dysfunction and depression-like behaviors in MI mice. Intriguingly, FMT-based intervention and concordance analysis of gut microbiota before and after FMT suggested that Prevotellaceae NK3B31 group, Alloprevotella, and Prevotellaceae UCG-001 were associated with the beneficial effects of SOTA. Furthermore, functional prediction of gut microbiota and correlation analysis support the significance of these dynamic microbial communities. In conclusion, these findings suggest that SOTA could serve as a potential drug to ameliorate cardiac dysfunction and depressive symptoms in MI patients via through the gut-heart-brain axis.
期刊介绍:
Neurobiology of Disease is a major international journal at the interface between basic and clinical neuroscience. The journal provides a forum for the publication of top quality research papers on: molecular and cellular definitions of disease mechanisms, the neural systems and underpinning behavioral disorders, the genetics of inherited neurological and psychiatric diseases, nervous system aging, and findings relevant to the development of new therapies.