Emily C. Hoedt, Georgia Carroll, Bree Stephensen, Katie Togher, Mark Morrison, Veral Vishnoi, Samwel Makanyengo, Brian Draganic, Brendan McManus, Louise Clarke, Kalpesh Shah, Stephen R. Smith, Nicholas J. Talley, Simon Keely, Peter Pockney
{"title":"微漏研究:与吻合口漏相关的 16S 群落图谱和元基因组枪式测序特征","authors":"Emily C. Hoedt, Georgia Carroll, Bree Stephensen, Katie Togher, Mark Morrison, Veral Vishnoi, Samwel Makanyengo, Brian Draganic, Brendan McManus, Louise Clarke, Kalpesh Shah, Stephen R. Smith, Nicholas J. Talley, Simon Keely, Peter Pockney","doi":"10.1038/s44355-024-00006-8","DOIUrl":null,"url":null,"abstract":"Anastomotic leaks (AL) are the most severe complications of colorectal surgery. The cause of AL is unclear, but recent studies have implicated the intestinal microbiota in its development. We aimed to determine whether there is an identifiable microbial pattern in the mucosal microbiota associated with AL. A pragmatic series of 162 patients undergoing colorectal resection with anastomosis had swabs taken from the proximal and distal mucosa of the bowel resection immediately after the tissue was excised. DNA was extracted for 16S rRNA amplicon gene sequencing and a subset for metagenomic shotgun sequencing (MGS). The AL rate in the cohort was approximately 15% (25/162). The alpha diversity measures from the intraoperative swabs were all significantly increased for AL, and there were significant differences in the beta diversity measures for AL from both the 16S and MGS datasets. The predictive power of AL was more sensitive when both proximal and distal communities were considered, and the species-level classifier AUC-ROC was stronger for the MGS dataset than for the 16S data (AUC = 0.92 and 0.76, respectively). We also report, for the first time, the functional changes in intraoperative AL microbes and noted an increase in the relative abundance of pathways with fermentation end products. This result was also found in our murine model of anastomoses (n = 20). At the time of surgery, the mucosal microbiota of the anastomotic extremities exhibits subtle differences at the species level and altered fermentation capacity, which may be associated with AL outcomes. A greater understanding of these insights could improve AL prognosis and preoperative management to reduce the occurrence of this life-threatening condition.","PeriodicalId":501708,"journal":{"name":"npj Gut and Liver","volume":" ","pages":"1-14"},"PeriodicalIF":0.0000,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s44355-024-00006-8.pdf","citationCount":"0","resultStr":"{\"title\":\"The Microleaks study: 16S community profile and metagenomic shotgun sequencing signatures associated with anastomotic leak\",\"authors\":\"Emily C. Hoedt, Georgia Carroll, Bree Stephensen, Katie Togher, Mark Morrison, Veral Vishnoi, Samwel Makanyengo, Brian Draganic, Brendan McManus, Louise Clarke, Kalpesh Shah, Stephen R. Smith, Nicholas J. Talley, Simon Keely, Peter Pockney\",\"doi\":\"10.1038/s44355-024-00006-8\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"Anastomotic leaks (AL) are the most severe complications of colorectal surgery. The cause of AL is unclear, but recent studies have implicated the intestinal microbiota in its development. We aimed to determine whether there is an identifiable microbial pattern in the mucosal microbiota associated with AL. A pragmatic series of 162 patients undergoing colorectal resection with anastomosis had swabs taken from the proximal and distal mucosa of the bowel resection immediately after the tissue was excised. DNA was extracted for 16S rRNA amplicon gene sequencing and a subset for metagenomic shotgun sequencing (MGS). The AL rate in the cohort was approximately 15% (25/162). The alpha diversity measures from the intraoperative swabs were all significantly increased for AL, and there were significant differences in the beta diversity measures for AL from both the 16S and MGS datasets. The predictive power of AL was more sensitive when both proximal and distal communities were considered, and the species-level classifier AUC-ROC was stronger for the MGS dataset than for the 16S data (AUC = 0.92 and 0.76, respectively). We also report, for the first time, the functional changes in intraoperative AL microbes and noted an increase in the relative abundance of pathways with fermentation end products. This result was also found in our murine model of anastomoses (n = 20). At the time of surgery, the mucosal microbiota of the anastomotic extremities exhibits subtle differences at the species level and altered fermentation capacity, which may be associated with AL outcomes. A greater understanding of these insights could improve AL prognosis and preoperative management to reduce the occurrence of this life-threatening condition.\",\"PeriodicalId\":501708,\"journal\":{\"name\":\"npj Gut and Liver\",\"volume\":\" \",\"pages\":\"1-14\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2024-09-02\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.nature.com/articles/s44355-024-00006-8.pdf\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"npj Gut and Liver\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://www.nature.com/articles/s44355-024-00006-8\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"npj Gut and Liver","FirstCategoryId":"1085","ListUrlMain":"https://www.nature.com/articles/s44355-024-00006-8","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0
摘要
吻合口漏(AL)是结直肠手术最严重的并发症。AL的病因尚不清楚,但最近的研究表明肠道微生物群与AL的发生有关。我们旨在确定与 AL 相关的粘膜微生物群是否存在可识别的微生物模式。我们对 162 名接受吻合术结直肠切除术的患者进行了务实的系列研究,在切除肠道组织后立即从切除肠道的近端和远端粘膜上采集拭子。提取的 DNA 用于 16S rRNA 扩增子基因测序,一部分用于元基因组枪式测序(MGS)。队列中的 AL 率约为 15%(25/162)。术中拭子的α多样性测量值在AL时均显著增加,16S和MGS数据集的β多样性测量值在AL时也有显著差异。当同时考虑近端和远端群落时,AL 的预测能力更加灵敏,MGS 数据集的物种级分类器 AUC-ROC 比 16S 数据更强(AUC = 0.92 和 0.76,分别为 0.92 和 0.76)。我们还首次报告了术中 AL 微生物的功能变化,并注意到发酵终产物通路的相对丰度有所增加。这一结果也出现在我们的吻合口小鼠模型中(n = 20)。手术时,吻合口肢体粘膜微生物群在物种水平上表现出微妙的差异,发酵能力也发生了改变,这可能与 AL 的结果有关。进一步了解这些观点可以改善 AL 的预后和术前管理,从而减少这种危及生命的疾病的发生。
The Microleaks study: 16S community profile and metagenomic shotgun sequencing signatures associated with anastomotic leak
Anastomotic leaks (AL) are the most severe complications of colorectal surgery. The cause of AL is unclear, but recent studies have implicated the intestinal microbiota in its development. We aimed to determine whether there is an identifiable microbial pattern in the mucosal microbiota associated with AL. A pragmatic series of 162 patients undergoing colorectal resection with anastomosis had swabs taken from the proximal and distal mucosa of the bowel resection immediately after the tissue was excised. DNA was extracted for 16S rRNA amplicon gene sequencing and a subset for metagenomic shotgun sequencing (MGS). The AL rate in the cohort was approximately 15% (25/162). The alpha diversity measures from the intraoperative swabs were all significantly increased for AL, and there were significant differences in the beta diversity measures for AL from both the 16S and MGS datasets. The predictive power of AL was more sensitive when both proximal and distal communities were considered, and the species-level classifier AUC-ROC was stronger for the MGS dataset than for the 16S data (AUC = 0.92 and 0.76, respectively). We also report, for the first time, the functional changes in intraoperative AL microbes and noted an increase in the relative abundance of pathways with fermentation end products. This result was also found in our murine model of anastomoses (n = 20). At the time of surgery, the mucosal microbiota of the anastomotic extremities exhibits subtle differences at the species level and altered fermentation capacity, which may be associated with AL outcomes. A greater understanding of these insights could improve AL prognosis and preoperative management to reduce the occurrence of this life-threatening condition.