Adilah F Ahmad, Jose A Caparrós-Martin, Nicola Gray, Samantha Lodge, Julien Wist, Silvia Lee, Fergal O'Gara, Girish Dwivedi, Natalie C Ward
{"title":"Gut microbiota and metabolomics profiles in patients with chronic stable angina and acute coronary syndrome.","authors":"Adilah F Ahmad, Jose A Caparrós-Martin, Nicola Gray, Samantha Lodge, Julien Wist, Silvia Lee, Fergal O'Gara, Girish Dwivedi, Natalie C Ward","doi":"10.1152/physiolgenomics.00072.2023","DOIUrl":null,"url":null,"abstract":"<p><p>Cardiovascular disease (CVD) is the leading cause of death worldwide. The gut microbiota and its associated metabolites may be involved in the development and progression of CVD, although the mechanisms and impact on clinical outcomes are not fully understood. This study investigated the gut microbiome profile and associated metabolites in patients with chronic stable angina (CSA) and acute coronary syndrome (ACS) compared with healthy controls. Bacterial alpha diversity in stool from patients with ACS or CSA was comparable to healthy controls at both baseline and follow-up visits. Differential abundance analysis identified operational taxonomic units (OTUs) assigned to commensal taxa differentiating patients with ACS from healthy controls at both baseline and follow-up. Patients with CSA and ACS had significantly higher levels of trimethylamine <i>N</i>-oxide compared with healthy controls (CSA: 0.032 ± 0.023 mmol/L, <i>P</i> < 0.01 vs. healthy, and ACS: 0.032 ± 0.023 mmol/L, <i>P</i> = 0.02 vs. healthy, respectively). Patients with ACS had reduced levels of propionate and butyrate (119 ± 4 vs. 139 ± 5.1 µM, <i>P</i> = 0.001, and 14 ± 4.3 vs. 23.5 ± 8.1 µM, <i>P</i> < 0.001, respectively), as well as elevated serum sCD14 (2245 ± 75.1 vs. 1834 ± 45.8 ng/mL, <i>P</i> < 0.0001) and sCD163 levels (457.3 ± 31.8 vs. 326.8 ± 20.7 ng/mL, <i>P</i> = 0.001), compared with healthy controls at baseline. Furthermore, a modified small molecule metabolomic and lipidomic signature was observed in patients with CSA and ACS compared with healthy controls. These findings provide evidence of a link between gut microbiome composition and gut bacterial metabolites with CVD. Future time course studies in patients to observe temporal changes and subsequent associations with gut microbiome composition are required to provide insight into how these are affected by transient changes following an acute coronary event.<b>NEW & NOTEWORTHY</b> The study found discriminative microorganisms differentiating patients with acute coronary syndrome (ACS) from healthy controls. In addition, reduced levels of certain bacterial metabolites and elevated sCD14 and sCD163 were observed in patients with ACS compared with healthy controls. Furthermore, modified small molecule metabolomic and lipidomic signatures were found in both patient groups. Although it is not known whether these differences in profiles are associated with disease development and/or progression, the findings provide exciting options for potential new disease-related mechanism(s) and associated therapeutic target(s).</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":null,"pages":null},"PeriodicalIF":4.6000,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"ACS Applied Bio Materials","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1152/physiolgenomics.00072.2023","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2023/10/9 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"MATERIALS SCIENCE, BIOMATERIALS","Score":null,"Total":0}
引用次数: 0
Abstract
Cardiovascular disease (CVD) is the leading cause of death worldwide. The gut microbiota and its associated metabolites may be involved in the development and progression of CVD, although the mechanisms and impact on clinical outcomes are not fully understood. This study investigated the gut microbiome profile and associated metabolites in patients with chronic stable angina (CSA) and acute coronary syndrome (ACS) compared with healthy controls. Bacterial alpha diversity in stool from patients with ACS or CSA was comparable to healthy controls at both baseline and follow-up visits. Differential abundance analysis identified operational taxonomic units (OTUs) assigned to commensal taxa differentiating patients with ACS from healthy controls at both baseline and follow-up. Patients with CSA and ACS had significantly higher levels of trimethylamine N-oxide compared with healthy controls (CSA: 0.032 ± 0.023 mmol/L, P < 0.01 vs. healthy, and ACS: 0.032 ± 0.023 mmol/L, P = 0.02 vs. healthy, respectively). Patients with ACS had reduced levels of propionate and butyrate (119 ± 4 vs. 139 ± 5.1 µM, P = 0.001, and 14 ± 4.3 vs. 23.5 ± 8.1 µM, P < 0.001, respectively), as well as elevated serum sCD14 (2245 ± 75.1 vs. 1834 ± 45.8 ng/mL, P < 0.0001) and sCD163 levels (457.3 ± 31.8 vs. 326.8 ± 20.7 ng/mL, P = 0.001), compared with healthy controls at baseline. Furthermore, a modified small molecule metabolomic and lipidomic signature was observed in patients with CSA and ACS compared with healthy controls. These findings provide evidence of a link between gut microbiome composition and gut bacterial metabolites with CVD. Future time course studies in patients to observe temporal changes and subsequent associations with gut microbiome composition are required to provide insight into how these are affected by transient changes following an acute coronary event.NEW & NOTEWORTHY The study found discriminative microorganisms differentiating patients with acute coronary syndrome (ACS) from healthy controls. In addition, reduced levels of certain bacterial metabolites and elevated sCD14 and sCD163 were observed in patients with ACS compared with healthy controls. Furthermore, modified small molecule metabolomic and lipidomic signatures were found in both patient groups. Although it is not known whether these differences in profiles are associated with disease development and/or progression, the findings provide exciting options for potential new disease-related mechanism(s) and associated therapeutic target(s).
心血管疾病(CVD)是全球死亡的主要原因。肠道微生物群及其相关代谢产物可能参与CVD的发展和进展,尽管其机制和对临床结果的影响尚不完全清楚。本研究调查了与健康对照组相比,慢性稳定型心绞痛(CSA)和急性冠状动脉综合征(ACS)患者的肠道微生物组特征和相关代谢产物。在基线和随访中,ACS或CSA患者粪便中的细菌α多样性与健康对照组相当。差异丰度分析确定了分配给共生类群的操作分类单元,在基线和随访时将ACS患者与健康对照区分开来。与健康对照组相比,CSA和ACS患者的三甲胺N-氧化物水平均显著较高(CSA;0.032±0.023 mmol/L,与健康对照和ACS相比,p 0.01;与健康对照分别为0.032±0.02 3mmol/L,p=0.02)。与基线时的健康对照组相比,ACS患者的丙酸盐和丁酸盐水平降低(119±4 vs 139±5.1µM,p=0.001和14±4.3 vs 23.5±8.1µM,p p=0.001)。此外,与健康对照组相比,CSA和ACS患者都观察到了改良的小分子代谢组学和脂质组学特征。这些发现为心血管疾病的肠道微生物组组成和肠道细菌代谢产物之间的联系提供了证据。