Rikeish R Muralitharan, Michael E Nakai, Matthew Snelson, Tenghao Zheng, Evany Dinakis, Liang Xie, Hamdi Jama, Madeleine Paterson, Waled Shihata, Flavia Wassef, Antony Vinh, Grant R Drummond, David M Kaye, Charles R Mackay, Francine Z Marques
{"title":"血管紧张素 II 对肠道微生物组的影响:与实验因素相比影响不大","authors":"Rikeish R Muralitharan, Michael E Nakai, Matthew Snelson, Tenghao Zheng, Evany Dinakis, Liang Xie, Hamdi Jama, Madeleine Paterson, Waled Shihata, Flavia Wassef, Antony Vinh, Grant R Drummond, David M Kaye, Charles R Mackay, Francine Z Marques","doi":"10.1093/cvr/cvae062","DOIUrl":null,"url":null,"abstract":"<p><strong>Aims: </strong>Animal models are regularly used to test the role of the gut microbiome in hypertension. Small-scale pre-clinical studies have investigated changes to the gut microbiome in the angiotensin II hypertensive model. However, the gut microbiome is influenced by internal and external experimental factors, which are not regularly considered in the study design. Once these factors are accounted for, it is unclear if microbiome signatures are reproduceable. We aimed to determine the influence of angiotensin II treatment on the gut microbiome using a large and diverse cohort of mice and to quantify the magnitude by which other factors contribute to microbiome variations.</p><p><strong>Methods and results: </strong>We conducted a retrospective study to establish a diverse mouse cohort resembling large human studies. We sequenced the V4 region of the 16S rRNA gene from 538 samples across the gastrointestinal tract of 303 male and female C57BL/6J mice randomized into sham or angiotensin II treatment from different genotypes, diets, animal facilities, and age groups. Analysing over 17 million sequencing reads, we observed that angiotensin II treatment influenced α-diversity (P = 0.0137) and β-diversity (i.e. composition of the microbiome, P < 0.001). Bacterial abundance analysis revealed patterns consistent with a reduction in short-chain fatty acid producers, microbial metabolites that lower blood pressure. Furthermore, animal facility, genotype, diet, age, sex, intestinal sampling site, and sequencing batch had significant effects on both α- and β-diversity (all P < 0.001). Sampling site (6.8%) and diet (6%) had the largest impact on the microbiome, while angiotensin II and sex had the smallest effect (each 0.4%).</p><p><strong>Conclusion: </strong>Our large-scale data confirmed findings from small-scale studies that angiotensin II impacted the gut microbiome. However, this effect was modest relative to most of the other factors studied. Accounting for these factors in future pre-clinical hypertensive studies will increase the likelihood that microbiome findings are replicable and translatable.</p>","PeriodicalId":9638,"journal":{"name":"Cardiovascular Research","volume":" ","pages":"1155-1163"},"PeriodicalIF":10.2000,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11368123/pdf/","citationCount":"0","resultStr":"{\"title\":\"Influence of angiotensin II on the gut microbiome: modest effects in comparison to experimental factors.\",\"authors\":\"Rikeish R Muralitharan, Michael E Nakai, Matthew Snelson, Tenghao Zheng, Evany Dinakis, Liang Xie, Hamdi Jama, Madeleine Paterson, Waled Shihata, Flavia Wassef, Antony Vinh, Grant R Drummond, David M Kaye, Charles R Mackay, Francine Z Marques\",\"doi\":\"10.1093/cvr/cvae062\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Aims: </strong>Animal models are regularly used to test the role of the gut microbiome in hypertension. Small-scale pre-clinical studies have investigated changes to the gut microbiome in the angiotensin II hypertensive model. However, the gut microbiome is influenced by internal and external experimental factors, which are not regularly considered in the study design. Once these factors are accounted for, it is unclear if microbiome signatures are reproduceable. We aimed to determine the influence of angiotensin II treatment on the gut microbiome using a large and diverse cohort of mice and to quantify the magnitude by which other factors contribute to microbiome variations.</p><p><strong>Methods and results: </strong>We conducted a retrospective study to establish a diverse mouse cohort resembling large human studies. We sequenced the V4 region of the 16S rRNA gene from 538 samples across the gastrointestinal tract of 303 male and female C57BL/6J mice randomized into sham or angiotensin II treatment from different genotypes, diets, animal facilities, and age groups. Analysing over 17 million sequencing reads, we observed that angiotensin II treatment influenced α-diversity (P = 0.0137) and β-diversity (i.e. composition of the microbiome, P < 0.001). Bacterial abundance analysis revealed patterns consistent with a reduction in short-chain fatty acid producers, microbial metabolites that lower blood pressure. Furthermore, animal facility, genotype, diet, age, sex, intestinal sampling site, and sequencing batch had significant effects on both α- and β-diversity (all P < 0.001). Sampling site (6.8%) and diet (6%) had the largest impact on the microbiome, while angiotensin II and sex had the smallest effect (each 0.4%).</p><p><strong>Conclusion: </strong>Our large-scale data confirmed findings from small-scale studies that angiotensin II impacted the gut microbiome. However, this effect was modest relative to most of the other factors studied. Accounting for these factors in future pre-clinical hypertensive studies will increase the likelihood that microbiome findings are replicable and translatable.</p>\",\"PeriodicalId\":9638,\"journal\":{\"name\":\"Cardiovascular Research\",\"volume\":\" \",\"pages\":\"1155-1163\"},\"PeriodicalIF\":10.2000,\"publicationDate\":\"2024-09-02\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11368123/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Cardiovascular Research\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1093/cvr/cvae062\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CARDIAC & CARDIOVASCULAR SYSTEMS\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cardiovascular Research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1093/cvr/cvae062","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CARDIAC & CARDIOVASCULAR SYSTEMS","Score":null,"Total":0}
引用次数: 0
摘要
导言:动物模型经常被用来测试肠道微生物组在高血压中的作用。小规模临床前研究调查了血管紧张素 II 高血压模型中肠道微生物组的变化。然而,肠道微生物组受内部和外部实验因素的影响,而这些因素在研究设计中并未经常考虑到。一旦考虑了这些因素,目前还不清楚微生物组特征是否可以重现。我们的目的是利用一个大型、多样化的小鼠队列来确定血管紧张素 II 治疗对肠道微生物组的影响,并量化其他因素对微生物组变化的影响程度:我们进行了一项回顾性研究,以建立一个类似于大型人类研究的多样化小鼠队列。我们对来自不同基因型、饮食、动物设施和年龄组的 303 只随机接受假治疗或血管紧张素 II 治疗的雌雄 C57BL/6J 小鼠胃肠道 538 个样本的 16S rRNA 基因 V4 区域进行了测序。通过分析超过 1700 万个测序读数,我们观察到血管紧张素 II 治疗影响了 α 多样性(P = 0.0137)和 β 多样性(即微生物组的组成,P 结论):我们的大规模数据证实了小规模研究的结果,即血管紧张素 II 会影响肠道微生物组。然而,相对于所研究的大多数其他因素,这种影响并不明显。在未来的临床前高血压研究中考虑这些因素将提高微生物组研究结果的可复制性和可转化性。
Influence of angiotensin II on the gut microbiome: modest effects in comparison to experimental factors.
Aims: Animal models are regularly used to test the role of the gut microbiome in hypertension. Small-scale pre-clinical studies have investigated changes to the gut microbiome in the angiotensin II hypertensive model. However, the gut microbiome is influenced by internal and external experimental factors, which are not regularly considered in the study design. Once these factors are accounted for, it is unclear if microbiome signatures are reproduceable. We aimed to determine the influence of angiotensin II treatment on the gut microbiome using a large and diverse cohort of mice and to quantify the magnitude by which other factors contribute to microbiome variations.
Methods and results: We conducted a retrospective study to establish a diverse mouse cohort resembling large human studies. We sequenced the V4 region of the 16S rRNA gene from 538 samples across the gastrointestinal tract of 303 male and female C57BL/6J mice randomized into sham or angiotensin II treatment from different genotypes, diets, animal facilities, and age groups. Analysing over 17 million sequencing reads, we observed that angiotensin II treatment influenced α-diversity (P = 0.0137) and β-diversity (i.e. composition of the microbiome, P < 0.001). Bacterial abundance analysis revealed patterns consistent with a reduction in short-chain fatty acid producers, microbial metabolites that lower blood pressure. Furthermore, animal facility, genotype, diet, age, sex, intestinal sampling site, and sequencing batch had significant effects on both α- and β-diversity (all P < 0.001). Sampling site (6.8%) and diet (6%) had the largest impact on the microbiome, while angiotensin II and sex had the smallest effect (each 0.4%).
Conclusion: Our large-scale data confirmed findings from small-scale studies that angiotensin II impacted the gut microbiome. However, this effect was modest relative to most of the other factors studied. Accounting for these factors in future pre-clinical hypertensive studies will increase the likelihood that microbiome findings are replicable and translatable.
期刊介绍:
Cardiovascular Research
Journal Overview:
International journal of the European Society of Cardiology
Focuses on basic and translational research in cardiology and cardiovascular biology
Aims to enhance insight into cardiovascular disease mechanisms and innovation prospects
Submission Criteria:
Welcomes papers covering molecular, sub-cellular, cellular, organ, and organism levels
Accepts clinical proof-of-concept and translational studies
Manuscripts expected to provide significant contribution to cardiovascular biology and diseases