肠道菌群及其代谢产物在动脉粥样硬化发生发展中的作用

王艾云; 王雨婷; 蔡静; 倪若妍; 罗彩莹; 喻卓; 陈鹏

肠道菌群及其代谢产物在动脉粥样硬化发生发展中的作用

王艾云^{1, 2},
王雨婷^{1, 2},
蔡静^{1, 2},
倪若妍^{1, 2},
罗彩莹^{1, 2},
喻卓^3, ,,
陈鹏^{1, 2, ,}

1.
昆明医科大学药学院暨云南省天然药物药理重点实验室
2.
昆明医科大学现代生物医药产业学院，云南昆明　650500
3.
昆明医科大学第一附属医院心内科，云南昆明　650032

基金项目: 国家自然科学基金（82360088）；云南省科技厅-昆明医科大学应用基础研究联合专项基金资助项目（2201AY070001-001）；云南省科技厅-昆明医科大学应用基础研究联合专项基金资助项目（202101AY070001-020）；云南省老年疾病临床医学研究中心专项资金（202102AA310069）。

详细信息

作者简介:
王艾云（1999～），女，云南楚雄人，在读硕士研究生，主要从事老年病药理学的研究工作

王雨婷对本文有同等的贡献

通讯作者:
喻卓，E-mail：dryuzhuo@163.com

陈鹏，E-mail：ynkmcp@gmail.com

中图分类号: R543
计量
- 文章访问数: 18
- HTML全文浏览量: 14
- PDF下载量: 1
- 被引次数: 0
出版历程
- 收稿日期: 2024-09-23
- 网络出版日期: 2024-12-10

The Role of Intestinal Flora and Its Metabolites in The Development of Atherosclerosis

Aiyun WANG^{1, 2},
Yuting WANG^{1, 2},
Jing CAI^{1, 2},
Ruoyan NI^{1, 2},
Caiying LUO^{1, 2},
Zhuo YU^{3
, ,},
Peng CHEN^{1, 2
, ,}

1.
School of Pharmaceutical Sciences and Yunnan Key Laboratory of Pharmacology for Natural Products，Kunming Medical University
2.
College of Modern Biomedical Industry，Kunming Medical University，Kunming Yunnan 650500
3.
Dept. of Cardiology，The 1st Affiliated Hospital of Kunming Medical University，Kunming Yunnan 650032，China

摘要

摘要: 肠道菌群及其代谢产物对动脉粥样硬化（Atherosclerosis，AS）等心血管疾病的发生和发展起到重要作用，已经成为预防和治疗AS的重要影响因素。本文聚焦肠道微生态环境，主要阐述氧化三甲胺（Trimethylamine Oxide，TMAO）、短链脂肪酸（Short-chain Fatty Acids，SCFA）、苯乙酰谷氨酰胺（Phenylacetylglutamine，PAG）、脂多糖（Lipopolysaccharides，LPS）和胆汁酸（Bile Acids，BA）等肠道菌群代谢产物与AS的关系，同时探讨以调整肠道菌群及其代谢产物为出发点的AS治疗策略，期望为AS的预防和治疗开辟新途径。
- 肠道菌群 /
- 代谢产物 /
- 动脉粥样硬化 /
- 治疗
Abstract: Intestinal flora and their metabolites play an important role in the occurrence and development of cardiovascular diseases such as atherosclerosis （AS）, and have become an important target for the prevention and treatment of AS. In this paper, we focus on the intestinal microecological environment and focus on the relationship between intestinal flora metabolites such as trimethylamine oxide （TMAO）, short-chain fatty acids （SCFA）, phenylacetylglutamine （PAG）, lipopolysaccharides （LPS）, and bile acids （BA）, and AS. At the same time, we also discuss the therapeutic strategies of AS that start from adjusting the intestinal flora and its metabolites, with the hope of opening up a new avenue of AS prevention and treatment. We hope to open up new avenues for the prevention and treatment of AS.
- Intestinal flora /
- Metabolites /
- Atherosclerosis /
- Treatment

HTML全文

参考文献(40)

[1]	Zou Y,Song X,Liu N,et al. Intestinal flora: A potential new regulator of cardiovascular disease[J]. Aging Dis,2022,13(3):753-772. doi: 10.14336/AD.2021.1022
[2]	Anselmi G,Gagliardi L,Egidi G,et al. Gut microbiota and cardiovascular diseases: A critical review[J]. Cardiol Rev,2021,29(4):195-204. doi: 10.1097/CRD.0000000000000327
[3]	Libby P,Buring J E,Badimon L,et al. Atherosclerosis[J]. Nat Rev Dis Primers,2019,5(1):56-63. doi: 10.1038/s41572-019-0106-z
[4]	Verhaar BJH,Prodan A,Nieuwdorp M,et al. Gut microbiota in hypertension and atherosclerosis: A review[J]. Nutrients,2020,12(10):2982-2993. doi: 10.3390/nu12102982
[5]	Barreau F,Tisseyre C,Ménard S,et al. Titanium dioxide particles from the diet: involvement in the genesis of inflammatory bowel diseases and colorectal cancer[J]. Part Fibre Toxicol,2021,18(1):26-34. doi: 10.1186/s12989-021-00421-2
[6]	Wang X,Hou L,Cui M,et al. The traditional Chinese medicine and non-small cell lung cancer: from a gut microbiome perspective[J]. Front Cell Infect Microbiol,2023,13(1):1151557-1151563.
[7]	Agirman G,Yu KB,Hsiao EY. Signaling inflammation across the gut-brain axis[J]. Science,2021,374(6571):1087-1092. doi: 10.1126/science.abi6087
[8]	Zhao S,Khoo S,Ng SC,et al. Brain functional network and amino acid metabolism association in females with subclinical depression[J]. Int J Environ Res Public Health,2022,19(6):3321-3328. doi: 10.3390/ijerph19063321
[9]	Lou J,Cui S,Li J,et al. Causal relationship between the gut microbiome and basal cell carcinoma,melanoma skin cancer,ease of skin tanning: evidence from three two-sample mendelian randomisation studies[J]. Front Immunol,2024,15(3):1279680-1279685.
[10]	Zhao HR,Xian QC,Zhang XM,et al. Jianpi Huayu prescription prevents atherosclerosis by improving inflammation and reshaping the intestinal microbiota in ApoE-/- mice[J]. Cell Biochem Biophys,2024,82(3):2297-2319. doi: 10.1007/s12013-024-01341-6
[11]	Deng B,Tao L,Wang Y. Natural products against inflammation and atherosclerosis: Targeting on gut microbiota[J]. Front Microbiol,2022,13(2):997056-997061.
[12]	Yan Q,Zhai W,Yang C,et al. The relationship among physical activity,intestinal flora,and cardiovascular disease[J]. Cardiovasc Ther,2021,2021(4):3364418-3364423.
[13]	Li Y,Chen Y,Li Z,et al. Gut microbiome and atherosclerosis: A Mendelian randomization study[J]. Rev Cardiovasc Med,2024,25(2):41-47. doi: 10.31083/j.rcm2502041
[14]	Toya T,Corban MT,Marrietta E,et al. Coronary artery disease is associated with an altered gut microbiome composition[J]. PLoS One,2020,15(1):27147-27153.
[15]	Wang S,Zhang J,Wang Y,et al. NLRP3 inflammasome as a novel therapeutic target for heart failure[J]. Anatol J Cardiol,2022,26(1):15-22. doi: 10.5152/AnatolJCardiol.2021.580
[16]	Liu J,Zhang T,Wang Y,et al. Baicalin ameliorates neuropathology in repeated cerebral ischemia-reperfusion injury model mice by remodeling the gut microbiota[J]. Aging (Albany NY),2020,12(4):3791-3806. doi: 10.18632/aging.102846
[17]	Al-Hadlaq SM,Balto HA,Hassan WM,et al. Biomarkers of non-communicable chronic disease: an update on contemporary methods[J]. PeerJ,2022,10(4):12977-12983.
[18]	Oktaviono YH,Dyah Lamara A,Saputra PBT,et al. The roles of trimethylamine-N-oxide in atherosclerosis and its potential therapeutic aspect: A literature review[J]. Biomol Biomed,2023,23(6):936-948.
[19]	Li X,Geng J,Zhao J,et al. Trimethylamine N-Oxide exacerbates cardiac fibrosis via activating the NLRP3 inflammasome[J]. Front Physiol,2019,10(6):866-872.
[20]	Wang Z,Liu C,Wei J,et al. Network and experimental pharmacology on mechanism of Yixintai regulates the TMAO/PKC/NF-κB signaling pathway in treating heart failure[J]. Drug Des Devel Ther,2024,18(2):1415-1438.
[21]	Mutalub YB,Abdulwahab M,Mohammed A,et al. Gut microbiota modulation as a novel therapeutic strategy in cardiometabolic diseases[J]. Foods,2022,11(17):2575-2583. doi: 10.3390/foods11172575
[22]	Cantu-Jungles TM,Rasmussen HE,Hamaker BR. Potential of prebiotic butyrogenic fibers in Parkinson's disease[J]. Front Neurol,2019,10(4):663-672.
[23]	Yue M,Zhang L. Exploring the mechanistic interplay between gut microbiota and precocious puberty: A narrative review[J]. Microorganisms,2024,12(2):323-328. doi: 10.3390/microorganisms12020323
[24]	Shen X,Li L,Sun Z,et al. Gut microbiota and atherosclerosis—focusing on the plaque stability[J]. Front Cardiovasc Med,2021,8(5):668532-668543.
[25]	Hu X,Li H,Zhao X,et al. Multi-omics study reveals that statin therapy is associated with restoration of gut microbiota homeostasis and improvement in outcomes in patients with acute coronary syndrome[J]. Theranostics,2021,11(12):5778-5793. doi: 10.7150/thno.55946
[26]	Nemet I,Saha PP,Gupta N,et al. A cardiovascular disease-linked gut microbial metabolite acts via adrenergic receptors[J]. Cell,2020,180(5):862-877. doi: 10.1016/j.cell.2020.02.016
[27]	Hua J,Jia X,Zhang L,et al. The characterization of two-component system PmrA/PmrB in Cronobacter sakazakii[J]. Front Microbiol,2020,119(2):903-911.
[28]	Yoshida N,Emoto T,Yamashita T,et al. Bacteroides vulgatus and Bacteroides dorei reduce gut microbial lipopolysaccharide production and inhibit atherosclerosis[J]. Circulation,2018,138(22):2486-2498. doi: 10.1161/CIRCULATIONAHA.118.033714
[29]	Meessen ECE,Sips FLP,Eggink HM,et al. Model-based data analysis of individual human postprandial plasma bile acid responses indicates a major role for the gallbladder and intestine[J]. Physiol Rep,2020,8(5):14358-14364.
[30]	Reiman D,Layden BT,Dai Y. MiMeNet: Exploring microbiome-metabolome relationships using neural networks[J]. PLoS Comput Biol,2021,17(5):100-106
[31]	陈嫚,刘洪涛,林相豪,等. 基于肠道菌群及胆汁酸代谢探讨动脉粥样硬化的发病机制[J]. 现代中西医结合杂志,2022,31(05):709-713. doi: 10.3969/j.issn.1008-8849.2022.05.025
[32]	Li Y,Hou H,Wang X,et al. Diammonium Glycyrrhizinate Ameliorates Obesity Through Modulation of Gut Microbiota-Conjugated BAs-FXR Signaling[J]. Front Pharmacol,2021,12(5):796590-796576.
[33]	Ferrell JM,Chiang JYL. Understanding Bile Acid Signaling in Diabetes: From Pathophysiology to Therapeutic Targets[J]. Diabetes Metab J,2019,43(3):257-272. doi: 10.4093/dmj.2019.0043
[34]	Tindall AM,McLimans CJ,Petersen KS,et al. Walnuts and Vegetable Oils Containing Oleic Acid Differentially Affect the Gut Microbiota and Associations with Cardiovascular Risk Factors: Follow-up of a Randomized,Controlled,Feeding Trial in Adults at Risk for Cardiovascular Disease[J]. J Nutr,2020,150(4):806-817. doi: 10.1093/jn/nxz289
[35]	Liang H,Yu A,Wang Z,et al. Atherosclerotic patients with diabetes mellitus may break through the threshold of healthy TMAO levels formed by long-term statins therapy[J]. Heliyon,2023,9(2):13657-13663. doi: 10.1016/j.heliyon.2023.e13657
[36]	Kim ES,Yoon BH,Lee SM,et al. Fecal microbiota transplantation ameliorates atherosclerosis in mice with C1q/TNF-related protein 9 genetic deficiency[J]. Exp Mol Med,2022,54(2):103-114. doi: 10.1038/s12276-022-00728-w
[37]	Thomas J,Sachdeva M,Dhar S,et al. Delphi Consensus Statement on the Role of Probiotics in the Treatment of Atopic Dermatitis[J]. Cureus,2024,16(7):64583-64587.
[38]	Kappel BA,De Angelis L,Heiser M,et al. Cross-omics analysis revealed gut microbiome-related metabolic pathways underlying atherosclerosis development after antibiotics treatment[J]. Mol Metab,2020,36(3):100976-100982.
[39]	Li C,Zhu L,Dai Y,et al. Diet-Induced High Serum Levels of Trimethylamine-N-oxide Enhance the Cellular Inflammatory Response without Exacerbating Acute Intracerebral Hemorrhage Injury in Mice[J]. Oxid Med Cell Longev,2022,45(2):15747-15755.
[40]	Zhu Y,Shui X,Liang Z,et al. Gut microbiota metabolites as integral mediators in cardiovascular diseases (Review)[J]. Int J Mol Med,2020,46(3):936-948. doi: 10.3892/ijmm.2020.4674

相关文章(20)

[1]	牛俊杰, 姬文娟, 于拽拽. 肠道菌群、血清ET、PCT水平与脓毒症病情程度、预后的相关性, 昆明医科大学学报. 2024, 45(4): 140-145. doi: 10.12259/j.issn.2095-610X.S20240420
[2]	李媛媛, 宋亚贤, 徐玉善, 曾晓甫, 袁惠, 徐兆, 江艳. 肠道菌群代谢物TMAO与非酒精性脂肪性肝病的关系, 昆明医科大学学报. 2024, 45(2): 77-84. doi: 10.12259/j.issn.2095-610X.S20240210
[3]	徐琳, 高开成, 贾杰, 李煜阳, 王华伟, 况轶群, 赵昱. 参苓白术散对甲基苯丙胺诱导小鼠肠道菌群改变的作用机制研究, 昆明医科大学学报. 2023, 44(8): 37-43. doi: 10.12259/j.issn.2095-610X.S20230829
[4]	邓绍友, 赵玉兰, 王佩锦, 李蓉, 李进涛, 郑红. 恒古骨伤愈合剂联合广谱抗生素改善db/db小鼠胰岛素抵抗和肠道菌群, 昆明医科大学学报. 2023, 44(5): 12-18. doi: 10.12259/j.issn.2095-610X.S20230530
[5]	李露, 田云粉. 肠道菌群与儿童非酒精性脂肪性肝病的研究进展, 昆明医科大学学报. 2023, 44(7): 148-155. doi: 10.12259/j.issn.2095-610X.S20230708
[6]	李丹, 万绪莲, 李律宇, 云宇, 罗光云, 刘韦兵, 林公府, 李宁, 黎勇坤, 段为钢. 尿酸酶缺失大鼠肠道菌群的变化, 昆明医科大学学报. 2023, 44(2): 27-32. doi: 10.12259/j.issn.2095-610X.S20230205
[7]	梁彩红, 孟明耀, 李欣欣, 熊晶晶, 李檬, 刘梅, 侯宗柳, 黄永坤. 肠道菌群代谢物脱氧胆酸对人脐带间充质干细胞hUC-MSCs增殖及细胞周期的影响, 昆明医科大学学报. 2023, 44(4): 23-30. doi: 10.12259/j.issn.2095-610X.S20230402
[8]	杨顺航, 李炯明, 刘建和, 王光, 李沛. 肠源性高草酸尿症的发病机制与治疗进展, 昆明医科大学学报. 2022, 43(7): 152-155. doi: 10.12259/j.issn.2095-610X.S20220734
[9]	刘演龙, 光雪峰, 尹小龙, 戴海龙. miR-125a-3p对动脉粥样硬化斑块及M1/M2巨噬细胞、MMP-9和VEGF的影响, 昆明医科大学学报. 2022, 43(9): 1-6. doi: 10.12259/j.issn.2095-610X.S20220915
[10]	刘四香, 黄永坤, 王明英, 胡红卫, 马敏, 凌昱. 功能性便秘患儿的肠道菌群分析及治疗干预, 昆明医科大学学报. 2022, 43(3): 123-127. doi: 10.12259/j.issn.2095-610X.S20220309
[11]	张莉, 王雨婷, 石佳宁, 余丹, 杨仁华, 沈志强, 龙江, 陈鹏. 基于网络药理学分析灯盏乙素治疗动脉粥样硬化的分子机制和体内验证, 昆明医科大学学报. 2022, 43(8): 17-27. doi: 10.12259/j.issn.2095-610X.S20220804
[12]	梁睿, 淳于纬训, 沈焘, 孙乐, 李云峰. 肠道菌群和免疫在结直肠肿瘤中作用研究进展, 昆明医科大学学报. 2020, 41(06): 156-161.
[13]	薛平燕, 江艳, 徐玉善, 袁惠, 李璇, 宋亚贤, 刘华. 肠道菌群结构在非酒精性脂肪性肝病患者中的改变, 昆明医科大学学报. 2020, 41(11): 62-67. doi: 10.12259/j.issn.2095-610X.S20201120
[14]	戴海龙, 王南, 陈晓晴, 何臻一, 冯晓岚, 光雪峰. 冠心病患者肠道菌群的特征, 昆明医科大学学报. 2020, 41(12): 36-41. doi: 10.12259/j.issn.2095-610X.S20201213
[15]	兰丹凤. Klotho基因G-395A多态性与2型糖尿病患者并发动脉粥样硬化的相关性, 昆明医科大学学报. 2015, 36(09): -1.
[16]	呼延婕. 白藜芦醇在治疗动脉粥样硬化中关键信号通路mTOR和STAT3转导机制的研究进展, 昆明医科大学学报. 2013, 34(01): -.
[17]	王玲. 2型糖尿病患者下肢动脉粥样硬化与骨密度改变的研究, 昆明医科大学学报. 2012, 33(02): -.
[18]	徐镇平. 芒果苷代谢产物1,3,6,7-四羟基三口酮的全合成, 昆明医科大学学报. 2012, 33(05): -.
[19]	. 普罗布考治疗动脉粥样硬化40例临床疗效观察, 昆明医科大学学报. 2011, 32(09): -.
[20]	丘红梅. 代谢综合征与颈动脉内膜中层厚度关系的研究, 昆明医科大学学报. 2009, 30(01): -.