CHINESE JOURNAL OF MEDICINAL GUIDE >
Causal Relationship Between Gut Microbiota and Vascular Aging: A Mendelian Randomization Study
Received date: 2026-05-20
Revised date: 2026-07-02
Accepted date: 2026-08-13
Online published: 2026-08-17
Objective: To explore the potential causal relationship between gut microbiota and vascular aging (VA) using Mendelian randomization (MR) analysis,to provide genetic causal evidence for the clinical treatment of vascular aging.Methods: Summary statistics from genome-wide association studies (GWAS) of gut microbiota in the MiBioGen consortium were used as exposure variables. Two-sample MR analysis was performed using public GWAS data to investigate the association between gut microbiota and vascular aging. Three analytical methods, namely inverse variance weighting (IVW), MR-Egger regression, and weighted median estimator (WME), were applied to assess causal relationships, with odds ratios (OR) and 95% confidence intervals (CI) as effect indicators. Egger intercept test, leave-one-out analysis, and MR-PRESSO were used for pleiotropy testing, sensitivity analysis, and outlier detection to ensure the reliability of the results.Results: IVW analysis identified five genera as protective factors against vascular aging: Anaerotruncus (OR=0.965, P=0.044, 95%CI: 0.931-0.999), Oscillibacter (OR=0.969, P=0.048, 95%CI: 0.939-1.000), Streptococcus (OR=0.971, P=0.046, 95%CI: 0.943-1.000), Ruminiclostridium 9 (OR=0.956, P=0.022, 95%CI: 0.920-0.994), and Ruminococcaceae UCG014 (OR=0.923, P=0.027, 95%CI: 0.931-0.996). Conversely, three genera were identified as potential risk factors: Flavonifractor (OR=1.057, P=0.006, 95%CI: 1.016-1.100), Eubacterium xylanophilum group (OR=1.044, P=0.032, 95%CI: 1.004-1.087), and Ruminococcaceae UCG002 (OR=1.036, P=0.010, 95%CI: 1.009-1.064).Conclusion: A potential causal association exists between gut microbiota and vascular aging. This study provides robust genetic evidence supporting the "gut-vascular axis" theory and identifies specific microbial targets with potential intervention value.
111 111 111
.
Causal Relationship Between Gut Microbiota and
Vascular Aging: A Mendelian Randomization Study
[1] 中华医学会老年医学分会.血管衰老临床评估与干预中国专家共识(2024版)[J].中华老年医学杂志,2024,43(11):1371-1381.
[2] 王靖怡,王阶,高嘉良.血管衰老的中医机理与防治策略[J].中华中医药杂志,2025,40(6):3001-3005.
[3] 中国老年医学学会高血压分会.脉搏波传导速度检测用于早期血管衰老评价的中国专家共识[J].中华高血压杂志,2021,29(12):1168-1172.
[4] Zhuang Miaomiao, Zhang Xun, Cai Jun. Microbiota-gut-brain axis: interplay between microbiota, barrier function and lymphatic system[J].Gut Microbes,2024,16(1):2387800.
[5] Prida S, Sharma D. The microbiome-estrogen connection and breast cancer risk[J].Cells, 2019,8(12):1642-1661.
[6] O'Riordan KJ, Moloney GM, Keane L, et al. The gut microbiota-immune-brain axis: therapeutic implications[J].Cell Rep Med, 2025,6(3):101982.
[7] Saeedi Saravi SS, Pugin B, Constancias F, et al. Gut microbiota-dependent increase in phenylacetic acid induces endothelial cell senescence during aging[J].Nat Aging, 2025,5(6):1025-1045.
[8] 汪鸣,刘生发,张滋龙,等.基于孟德尔随机化研究肠道菌群与缺血性脑卒中的因果关系[J].中国微生态学杂志,2024,36(8):892-899,906.
[9] Fan Yadong, Xu Chen, Xie Lulu, et al. Abnormal bile acid metabolism is an important feature of gut microbiota and fecal metabolites in patients with slow transit constipation[J].Front Cell Infect Microbiol, 2022,12:956528.
[10] Frolova MS, Suvorova IA, Iablokov SN, et al.Genomic reconstruction of short-chain fatty acid production by the human gut microbiota[J].Front Mol Biosci, 2022,9:949563.
[11] Mannerová S, Pantůček R, Doškař J, et al Macrococcus brunensis sp. nov., Macrococcus hajekii sp. nov. and Macrococcus lamae sp. nov., from the skin of llamas[J].Int J Syst Evol Microbiol, 2003,53(5):1647-1654.
[12] Lawson PA, Song Yuli, Liu Chengxu, et al. Anaerotruncus colihominis gen. nov., sp. nov., from human faeces[J].Int J Syst Evol Microbiol, 2004,54(2):413-417.
[13] Robles-Vera I, Toral M, de la Visitación N,et al. Protective effects of short-chain fatty acids on endothelial dysfunction induced by angiotensin II[J].Front Physiol, 2020,11:277.
[14] Yan Jianlong,Pan Yanbin,Shao Wenming, et al.Beneficial effect of the short-chain fatty acid propionate on vascular calcification through intestinal microbiota remodelling[J].Microbiome,2022,10(1):195-225.
[15] Duan Hongliang,Wang Lijuan,Huangfu Mingmei, et al .The impact of microbiota-derived short-chain fatty acids on macrophage activities in disease: Mechanisms and therapeutic potentials[J].Biomed Pharmacother,2023,165:115276.
[16] Kim YJ, Jung DH, Park CS.Important roles of Ruminococcaceae in the human intestine for resistant starch utilization[J].Food Sci Biotechnol, 2024,33(9):2009-2019.
[17] Liu Hao,Xi Qiulei,Tan Shanjun, et al.The metabolite butyrate produced by gut microbiota inhibits cachexia-associated skeletal muscle atrophy by regulating intestinal barrier function and macrophage polarization[J].Int Immunopharmacol, 2023,124(Pt B):111001.
[18] Li Chenhao, Stražar M, Mohamed AMT, et al. Gut microbiome and metabolome profiling in framingham heart study reveals cholesterol-metabolizing bacteria[J].Cell, 2024,187(8):1834-1852.e19.
[19] Cretoiu D, Ionescu RF, Enache RM, et al. Gut microbiome, functional food, atherosclerosis, and vascular calcifications—is there a missing link?[J].Microorganisms, 2021,9(9):1913.
[20] Jie Zhuye, Xia Huihua, Zhong Shilong, et al. The gut microbiome in atherosclerotic cardiovascular disease[J].Nat Commun, 2017,8(1):845.
[21] Chen Si, Nie Rui, Wang Chao, et al. Causal effects of the gut microbiome on immune-related vasculitis: a two-sample mendelian randomization study[A].Sci Rep, 2024,14(1):18810.
[22] Li Meng, Qian Mengqi, Jiang Qian, et al. Evidence of flavonoids on disease prevention[J].Antioxidants (Basel), 2023,12(2):527-546.
[23] Li Lingru,Li Tianxing,Liang Xue, et al.A decrease in flavonifractor plautii and its product, phytosphingosine, predisposes individuals with phlegm-dampness constitution to metabolic disorders[J].Cell Discov, 2025,11(1):25-46.
[24] Chen Wujun,Zhang Shun,Wu Jianfeng, et al.Butyrate-producing bacteria and the gut-heart axis in atherosclerosis[J].Clin Chim Acta, 2020,507:236-241.
[25] Koh A, Molinaro A, Ståhlman M, et al.Microbially produced imidazole propionate impairs insulin signaling through mTORC1[J].Cell, 2018,175(4):947-961.e17.
[26] Burgess S, Davey Smith G, Davies NM, et al.Guidelines for performing mendelian randomization investigations: update for summer 2023[J].Wellcome Open Res, 2023,4:186.
/
| 〈 |
|
〉 |