氧化三甲胺与心房颤动相关的研究进展

陈先慧; 马玉兰

doi:10.16766/j.cnki.issn.1674-4152.003560

氧化三甲胺与心房颤动相关的研究进展

doi: 10.16766/j.cnki.issn.1674-4152.003560

陈先慧¹,
马玉兰^2, ,

1.
青海大学研究生院，青海西宁 810016
2.
青海省心脑血管病专科医院青海省高原医学科学研究院青海西宁 810012

基金项目:

国家自然科学基金地区科学基金项目 81760084

详细信息

通讯作者:
马玉兰，E-mail：mylfamai@163.com

中图分类号: R541.75
计量
- 文章访问数: 38
- HTML全文浏览量: 17
- PDF下载量: 5
- 被引次数: 0
出版历程
- 收稿日期: 2023-11-16
- 网络出版日期: 2024-07-22

Research progress on the relationship between trimethylamine oxide and atrial fibrillation

CHEN Xianhui¹,
MA Yulan^{2
, ,}

1.
Graduate School of Qinghai University, Xi' ning, Qinghai 810016, China

摘要

摘要: 肠道菌群是一个复杂的群落，它与宿主的动态功能相互作用，适当的肠道微生物群结构和代谢物功能对于维持体内平衡至关重要。近些年，大量研究证明肠道菌群及其衍生代谢物影响着心血管疾病的发生发展，其中就包括心律失常，而心房颤动是最常见的心律失常之一。氧化三甲胺(TMAO)是目前研究最多的肠道菌群衍生代谢物之一，研究发现TMAO与心房颤动的发生发展密切相关。很多流行病学研究表明，TMAO在心房颤动的发生、发展及预后中发挥作用。TMAO通过促进多种心血管危险因素的发生来增加心房颤动易感性。此外，TMAO还可通过激发炎症反应、致使心脏纤维化与心房焦亡来促进心房结构的重构，其水平升高还可增加心房电生理不稳定性，引发异位活动致电生理重构，亦可直接或间接激活自主神经系统引起神经重塑而诱发心房颤动。另外，TMAO水平升高可诱导血小板高反应性，从而促进动脉血栓形成提高心房颤动血栓栓塞发生率，并且与消融术后心房颤动复发也明显相关。研究发现，TMAO在心房颤动防治方面有着一定的潜在价值。在饮食习惯上可以通过减少摄入生成三甲胺的膳食前体从而减少循环中TMAO水平、通过某些药物增加TMAO从肾脏的排泄以及直接服用益生元、益生菌或通过粪便菌群移植的方法调节肠道菌群构成，进而改变肠道菌群衍生代谢物水平。本文根据相关文献的研究结果从上述方面进行综述，以期为今后的相关研究提供一定的理论依据。
- 氧化三甲胺 /
- 心房颤动 /
- 肠道菌群
Abstract: The gut microbiota is a complex community that interacts with the dynamic functions of the host, and proper gut microbiota structure and metabolite function are essential for maintaining homeostasis. In recent years, a large number of studies have demonstrated that the gut microbiota and its derived metabolites influence the development of cardiovascular diseases, including cardiac arrhythmias, of which atrial fibrillation is one of the most common. Trimethylamine oxide (TMAO) is one of the most studied gut microbiota-derived metabolites, and TMAO has been found to be strongly associated with the development of atrial fibrillation. Many epidemiological studies have shown that TMAO plays a role in the onset, development and prognosis of atrial fibrillation (AF). TMAO increases the susceptibility to AF by contributing to the development of multiple cardiovascular risk factors. In addition, TMAO promotes atrial structural remodeling by stimulating inflammatory responses, causing cardiac fibrosis and atrial pyroptosis. Elevated levels of TMAO also increase atrial electrophysiological instability, triggering ectopic activity that leads to electrophysiological remodeling, and directly or indirectly activate the autonomic nervous system to cause neural remodeling that induces atrial fibrillation. In addition, elevated levels of TMAO induce platelet hyper-reactivity, which promotes arterial thrombosis, increases the incidence of thromboembolism in AF, and is also significantly associated with AF recurrence after ablation. TMAO has been shown to have some potential values in the prevention and treatment of AF. The composition of the gut microbiota can be modulated through dietary habits by reducing the intake of trimethylamine-producing dietary precursors and thereby reducing circulating levels of TMAO, by increasing the excretion of TMAO from the kidneys through certain drugs, and by directly taking prebiotics, probiotics, or through fecal flora transplantation, which can in turn alter the levels of gut microbiota -derived metabolites. In this paper, we review the above aspects based on the findings of the related literature, with the aim of providing a theoretical basis for future related studies.
- Trimethylamine oxide /
- Atrial fibrillation /
- Gut microbiota

HTML全文

图 1 TMAO促进心房颤动的发生机制

Figure 1. The mechanism of TMAO promoting atrial fibrillation

下载: 全尺寸图片幻灯片

参考文献(44)

[1]	ZUO K, LI J, LI K B, et al. Disordered gut microbiota and alterations in metabolic patterns are associated with atrial fibrillation[J]. Giga science, 2019, 8: giz058. DOI: 10.1093/Gigascience/giz058.
[2]	SARIM R, TAYYIBA A N, HAMAYLE S, et al. Association of gut microbiome dysbiosis with the progression of atrial fibrillation: a systematic review[J]. Ann Noninvasive Electrocardiol, 2023, 28: e13059. DOI: 10.1111/anec.13059.
[3]	YANG W T, YANG R, ZHAO Q, et al. A systematic review and meta-analysis of the gut microbiotadependent metabolite trimethylamine N-oxide with the incidence of atrial fibrillation[J]. Ann Palliat Med, 2021, 10(11): 11512-11523. doi: 10.21037/apm-21-2763
[4]	XU J, YANG Y J. Gut microbiome and its metaomics perspectives: profound implications for cardiovascular diseases[J]. Gut Microbes, 2021, 13(1): e1936379. DOI: 10.1080/19490976.2021.1936379.
[5]	GATAREK P, KALUZNA-CZAPLINSKA J. Trimethylamine N-oxide (TMAO) in human health[J]. Excli J, 2021, 20: 301-319.
[6]	ZHEN J, ZHOU Z, HE M, et al. The gut microbial metabolite trimethylamine N-oxide and cardiovascular diseases[J]. Front Endocrinol, 2023, 14: 1085041. DOI: 10.3389/fendo.2023.1085041.
[7]	SVINGEN G F T, ZUO H, UELAND P M, et al. Increased plasma trimethylamine-N-oxide is associated with incident atrial fibrillation[J]. Int J Cardiol, 2018, 267: 100-106. doi: 10.1016/j.ijcard.2018.04.128
[8]	XU F, FU Y, SUN T Y, et al. The interplay between host genetics and the gut microbiome reveals common and distinct microbiome features for complex human diseases[J]. Microbiome, 2020, 8(1): 145. DOI: 10.1186/s40168-020-00923-9.
[9]	ZUO K, LIU X Q, WANG P, et al. Metagenomic data-mining reveals enrichment of trimethylamine-N-oxide synthesis in gut microbiome in atrial fibrillation patients[J]. BMC Genomics, 2020, 21(1): 526. DOI: 10.1186/s12864-020-06944-w.
[10]	ANDREEA-IOANA I, MARIA-ADRIANA N, ANCA-ELENA C, et al. Gut molecules in cardiometabolic diseases: the mechanisms behind the story[J]. Int J Mol Sci, 2023, 24: 3385. DOI: 10.3390/ijms24043385.
[11]	MONIKA G, THOMAS A A, ARNELA S, et al. Gut microbiota, dysbiosis and atrial fibrillation. Arrhythmogenic mechanisms and potential clinical implications[J]. Cardiovasc Res, 2022, 118(11): 2415-2427. doi: 10.1093/cvr/cvab292
[12]	HOSEINI T Z, HASANI R S. Targeting TMAO and its metabolic pathway for cardiovascular diseases treatment[J]. J Diabetes Metab Disord, 2021, 20(1): 1095-1097. doi: 10.1007/s40200-021-00819-x
[13]	ZHOU X, JIN M, LIU L, et al. Trimethylamine N-oxide and cardiovascular outcomes in patients with chronic heart failure after myocardial infarction[J]. ESC Heart Fail, 2020, 7(1): 188-193.
[14]	GENG J, YANG C C, WANG B J, et al. Trimethylamine N-oxide promotes atherosclerosis via CD36-dependent MAPK/JNK pathway[J]. Biomed Pharmacother, 2018, 97: 941-947. doi: 10.1016/j.biopha.2017.11.016
[15]	LUO T, LIU D, GUO Z, et al. Deficiency of proline/serine-rich coiled-coil protein 1 (PSRC1) accelerates trimethylamine N-oxide-induced atherosclerosis in ApoE^-/- mice[J]. Mol Cell Cardiol, 2022, 70: 60-74.
[16]	杨晓明, 郑祥, 王超超. 肠道菌群代谢产物与冠心病合并慢性心力衰竭的相关性及对患者预后水平的预测作用[J]. 中华全科医学, 2023, 21(10): 1676-1678, 1718. doi: 10.16766/j.cnki.issn.1674-4152.003198 YANG X M. ZHENG X, WANG C C. Correlation between gut microbiota metabolites and coronary heart disease combined with chronic heart failure and its predictive role in patient prognosis[J]. Chinese Journal of General Practice, 2023, 21(10): 1676-1678, 1718. doi: 10.16766/j.cnki.issn.1674-4152.003198
[17]	CORBAN M T, TOYA T, AHMAD A, et al. Atrial fibrillation and endothelial dysfunction: a potential link?[J]. Mayo Clin Proc, 2021, 96(6): 1609-1621. doi: 10.1016/j.mayocp.2020.11.005
[18]	GE X Y, LIANG Z, ZHUANG R L, et al. The gut microbial metabolite trimethylamine N-oxide and hypertension risk: a systematic review and dose-response meta-analysis[J]. Adv Nutr, 2020, 11(1): 66-76. doi: 10.1093/advances/nmz064
[19]	BVTTNER P, OKUN J G, HAUKE J, et al. Trimethylamine N-oxide in atrial fibrillation progression[J]. Int J Heart Vasc, 2020, 29: 100554. DOI: 10.1016/j.ijcha.2020.100554.
[20]	LIU M, HAN Q, YANG J. Trimethylamine-N-oxide (TMAO) increased aquaporin-2 expression in spontaneously hypertensive rats[J]. Clin Exp Hypertens, 2019, 41(4): 312-322. doi: 10.1080/10641963.2018.1481420
[21]	DAGFNN A, YAHYA M S, ELSA K, et al. Blood pressure, hypertension and the risk of atrial fbrillation: a systematic review and meta-analysis of cohort studies[J]. Eur J Epidemiol, 2023, 38: 145-178. doi: 10.1007/s10654-022-00914-0
[22]	LI X L, GENG J, ZHAO J X, et al. Trimethylamine N-oxide exacerbates cardiac fibrosis via activating the NLRP3 inflammasome[J]. Front Physiol, 2019, 10: 866. DOI: 10.3389/fphys.2019.00866.
[23]	TABATA T, YAMASHITA T, HOSOMI K, et al. Gut microbial composition in patients with atrial fibrillation: effects of diet and drugs[J]. Heart Vessels, 2021, 36(1): 105-114. doi: 10.1007/s00380-020-01669-y
[24]	YANG W, ZHAO Q, YAO M, et al. The transformation of atrial fibroblasts into myofibroblasts is promoted by trimethylamine N-oxide via the Wnt3a/β-catenin signaling pathway[J]. J Thorac Dis, 2022, 14(5): 1526-1536. doi: 10.21037/jtd-22-475
[25]	HUANG R, LI Y, LEI Y H. The gut microboal-derived metabolite trimethyamine n-oxide and atrial fibrillation: relationships, mechanisms, and therapeutic strategies[J]. Clin interv Aging, 2021, 16: 1975-1986. DOI: 10.2147/CIA.S339590.
[26]	WANG G J, KONG B, SHUAI W, et al. 3, 3-Dimethyl-1-butanol attenuates cardiac remodeling in pressure-overload-induced heart failure mice[J]. J Nutr Biochem, 2020, 78: 108341. DOI: 10.1016/j.jnutbio.2020.108341.
[27]	LUO Y C, ZAHNG Y, HAN X J, et al. Akkermansia muciniphila prevents cold-related atrial fibrillation in rats by modulation of TMAO induced cardiac pyroptosis[J]. E Bio Med, 2022, 82: 104087. DOI: 10.1016/j.ebiom.2022.104087.
[28]	MICHELLE T L, DARAE K, LINDSAY M A, et al. Gastrointestinal and liver diseases and atrial fibrillation: a review of the literature[J]. Therap Adv Gastroenterol, 2019, 12: 1-19. DOI: 10.1177/1756284819832237.
[29]	MENG G N, ZHOU X A, WANG M L, et al. Gut microbe-derived metabolite trimethylamine N-oxide activates the cardiac autonomic nervous system and facilitates ischemia-induced ventricular arrhythmia via two different pathways[J]. E Bio Med, 2019, 44: 656-664.
[30]	YU L, MENG G, HUANG B, et al. A potential relationship between gut microbes and atrial fibrillation: trimethylamine N-oxide, a gut microbe-derived metabolite, facilitates the progression of atrial fibrillation[J]. Int J Cardiol, 2018, 255: 92-98. doi: 10.1016/j.ijcard.2017.11.071
[31]	HUANG R, LI Y, LEI Y H. The gut microboal-derived metabolite trimethyamine N-oxide and atrial fibrillation: relationships, mechanisms, and therapeutic strategies[J]. Clin interv Aging, 2021, 16: 1975-1986. doi: 10.2147/CIA.S339590
[32]	LIANG Z G, DONG Z X, GUO M H, et al. Trimethyiamine N-oxide as a risk marker for ischemic stroke in patients with atrial fibrillation[J]. J Biochem Mol Toxiciol, 2019, 33: e22246. DOI: 10.1002/jbt.22246.
[33]	LUCIANI M, MVLLER D, VANETTA C, et al. Trimethylamine-N-oxide is associated with cardiovascular mortality and vascular brain lesions in patients with atrialfibrillation[J]. Heart, 2023, 109(5): 396-404.
[34]	GONG D X, ZHANG L, ZHANG Y, et al. Gut microbial metabolite trimethylamine N-oxide is related to thrombus formation in atrial fibrillation patients[J]. Am J Med Sci, 2019, 358(6): 422-428. doi: 10.1016/j.amjms.2019.09.002
[35]	HUYNH K. Novel gut microbiota-derived metabolite promotes platelet thrombosis via adrenergic receptor signalling[J]. Nat Rev Cardiol, 2020, 17(5): 265. doi: 10.1038/s41569-020-0367-y
[36]	KONIECZNY R, ZŻURAWSKA-P E, KAAZ K, et al. All-cause mortality and trimethylamine N-oxide levels in patients with cardiovascular disease[J]. Cardiology, 2022, 147(4): 443-452. doi: 10.1159/000525972
[37]	ZUO K, LI J, WANG P, et al. Duration of persistent atrial fibrillation is associated with alterations in human gut microbiota and metabolic phenotypes[J]. mSystems, 2019, 4(6): e00422-19. DOI: 10.1128/mSystems.00422-19.
[38]	ZUO K, FANG C, LIU Z. Commensal microbederived SCFA alleviates atrial fibrillation via GPR43/NLRP3signaling[J]. Int J Biol Sci, 2022, 18(10): 4219-4232. doi: 10.7150/ijbs.70644
[39]	RASHID S, NOOR TA, SAEED H, et al. Association of gut microbiome dysbiosis with the progression of atrial fibrillation: a systematic review[J]. Ann Noninvasive Electrocardiol, 2023, 28(4): e13059. DOI: 10.1111/anec.13059.
[40]	ALDANA-HERNANDEZ P, LEONARD K A, ZHAO Y Y, et al. Dietary choline or trimethylamine N-oxide supplementation does not influence atherosclerosis development in Ldlr-/- and Apoe-/- male mice[J]. J Nutr, 2020, 150: 249-255. doi: 10.1093/jn/nxz214
[41]	GAWAŁKO M, LINZ D, DOBREV D. Gut-microbiota derived TMAO: a risk factor, a mediator or a bystander in the pathogenesis of atrial fibrillation?[J]. Int J Cardiol Heart Vasc, 2021, 34: 100818. DOI: 10.1016/j.ijcha2021.100818.
[42]	SMITS L P, KOOTTE R S, LEVIN E, et al. Effect of vegan fecal microbiota transplantation on carnitine-and choline-derived trimethylamine-N-oxide production and vascular inflammation in patients with metabolic syndrome[J]. J Am Heart Assoc, 2018, 7(7): e008342. doi: 10.1161/JAHA.117.008342
[43]	CHI E, LI C, WU D, et al. Effects of probiotics on patientswith hypertension: a systematic review and meta-analysis[J]. Curr Hypertens Rep, 2020, 22(5): 34. DOI: 10.1007/s11906-020-01042-4.
[44]	ZHOU W Y, CHENG Y Y, ZHU P, et al. Implication of Gut Microbiota in Cardiovascular Diseases[J]. Oxid Med Cell Longev, 2020, DOI: 10.1155/2020/5394096.