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Published in: BMC Cardiovascular Disorders 1/2024

Open Access 01-12-2024 | Arterial Occlusive Disease | Research

Causality of the gut microbiome and atherosclerosis-related lipids: a bidirectional Mendelian Randomization study

Authors: Da Teng, Wenjuan Jia, Wenlong Wang, Lanlan Liao, Bowen Xu, Lei Gong, Haibin Dong, Lin Zhong, Jun Yang

Published in: BMC Cardiovascular Disorders | Issue 1/2024

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Abstract

Aims

Recent studies have indicated an association between intestinal flora and lipids. However, observational studies cannot indicate causality. In this study, we aimed to investigate the potentially causal relationships between the intestinal flora and blood lipids.

Methods

We performed a bidirectional two-sample Mendelian Randomization (MR) analysis to investigate the causal relationship between intestinal flora and blood lipids. Summary statistics of genome-wide association studies (GWASs) for the 211 intestinal flora and blood lipid traits (n = 5) were obtained from public datasets. Five recognized MR methods were applied to assess the causal relationship with lipids, among which, the inverse-variance weighted (IVW) regression was used as the primary MR method. A series of sensitivity analyses were performed to test the robustness of the causal estimates.

Results

The results indicated a potential causal association between 19 intestinal flora and dyslipidemia in humans. Genus Ruminococcaceae, Christensenellaceae, Parasutterella, Terrisporobacter, Parabacteroides, Class Erysipelotrichia, Family Erysipelotrichaceae, and order Erysipelotrichales were associated with higher dyslipidemia, whereas genus Oscillospira, Peptococcus, Ruminococcaceae UCG010, Ruminococcaceae UCG011, Dorea, and Family Desulfovibrionaceae were associated with lower dyslipidemia. After using the Bonferroni method for multiple testing correction, Only Desulfovibrionaceae [Estimate = -0.0418, 95% confidence interval [CI]: 0.9362–0.9826, P = 0.0007] exhibited stable and significant negative associations with ApoB levels. The inverse MR analysis did not find a significant causal effect of lipids on the intestinal flora. Additionally, no significant heterogeneity or horizontal pleiotropy for IVs was observed in the analysis.

Conclusion

The study suggested a causal relationship between intestinal flora and dyslipidemia. These findings will provide a meaningful reference to discover dyslipidemia for intervention to address the problems in the clinic.
Appendix
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Literature
1.
go back to reference Mensah GA, Roth GA, Fuster V. The Global Burden of Cardiovascular Diseases and Risk Factors: 2020 and Beyond. J Am Coll Cardiol. 2019;74(20):2529–32.PubMedCrossRef Mensah GA, Roth GA, Fuster V. The Global Burden of Cardiovascular Diseases and Risk Factors: 2020 and Beyond. J Am Coll Cardiol. 2019;74(20):2529–32.PubMedCrossRef
2.
go back to reference Virani SS, Alonso A, Aparicio HJ, et al. Heart Disease and Stroke Statistics-2021 Update: A Report From the American Heart Association. Circulation. 2021;143(8):e254–743.PubMedCrossRef Virani SS, Alonso A, Aparicio HJ, et al. Heart Disease and Stroke Statistics-2021 Update: A Report From the American Heart Association. Circulation. 2021;143(8):e254–743.PubMedCrossRef
3.
go back to reference Di Angelantonio E, Sarwar N, Perry P, et al. Major lipids, apolipoproteins, and risk of vascular disease. JAMA. 2009;302(18):1993–2000.PubMedCrossRef Di Angelantonio E, Sarwar N, Perry P, et al. Major lipids, apolipoproteins, and risk of vascular disease. JAMA. 2009;302(18):1993–2000.PubMedCrossRef
4.
go back to reference Sarwar N, Danesh J, Eiriksdottir G, et al. Triglycerides and the risk of coronary heart disease: 10,158 incident cases among 262,525 participants in 29 Western prospective studies. Circulation. 2007;115(4):450–8.PubMedCrossRef Sarwar N, Danesh J, Eiriksdottir G, et al. Triglycerides and the risk of coronary heart disease: 10,158 incident cases among 262,525 participants in 29 Western prospective studies. Circulation. 2007;115(4):450–8.PubMedCrossRef
5.
go back to reference Erqou S, Kaptoge S, Perry PL, et al. Lipoprotein(a) concentration and the risk of coronary heart disease, stroke, and nonvascular mortality. JAMA. 2009;302(4):412–23.PubMedCrossRef Erqou S, Kaptoge S, Perry PL, et al. Lipoprotein(a) concentration and the risk of coronary heart disease, stroke, and nonvascular mortality. JAMA. 2009;302(4):412–23.PubMedCrossRef
6.
go back to reference Feingold KR. Introduction to lipids and lipoproteins[A]. In: Endotext Feingold KR, Anawalt B, Blackman MR et al. (eds). South Dartmouth (MA): MDText.com, Inc.Copyright © 2000-2024, MDText.com, Inc., 2000; 2024. Feingold KR. Introduction to lipids and lipoproteins[A]. In: Endotext Feingold KR, Anawalt B, Blackman MR et al. (eds). South Dartmouth (MA): MDText.com, Inc.Copyright © 2000-2024, MDText.com, Inc., 2000; 2024.
7.
go back to reference Nayyer Uz Z, Dar MH, Adnan Y, et al. Nonfasting Apo-lipoprotein B and Triglyceride levels as a predictor of coronary heart disease in Type II diabetic patients. Pak J Med Sci. 2018;34(2):247–52. Nayyer Uz Z, Dar MH, Adnan Y, et al. Nonfasting Apo-lipoprotein B and Triglyceride levels as a predictor of coronary heart disease in Type II diabetic patients. Pak J Med Sci. 2018;34(2):247–52.
8.
go back to reference Vrablík M, Ceska R, Horínek A. Major apolipoprotein B-100 mutations in lipoprotein metabolism and atherosclerosis. Physiol Res. 2001;50(4):337–43.PubMed Vrablík M, Ceska R, Horínek A. Major apolipoprotein B-100 mutations in lipoprotein metabolism and atherosclerosis. Physiol Res. 2001;50(4):337–43.PubMed
9.
go back to reference Ostos MA, Conconi M, Vergnes L, et al. Antioxidative and antiatherosclerotic effects of human apolipoprotein A-IV in apolipoprotein E-deficient mice. Arterioscler Thromb Vasc Biol. 2001;21(6):1023–8.PubMedCrossRef Ostos MA, Conconi M, Vergnes L, et al. Antioxidative and antiatherosclerotic effects of human apolipoprotein A-IV in apolipoprotein E-deficient mice. Arterioscler Thromb Vasc Biol. 2001;21(6):1023–8.PubMedCrossRef
10.
go back to reference Qu J, Ko CW, Tso P, et al. Apolipoprotein A-IV: A Multifunctional Protein Involved in Protection against Atherosclerosis and Diabetes. Cells. 2019;8(4):319.PubMedPubMedCentralCrossRef Qu J, Ko CW, Tso P, et al. Apolipoprotein A-IV: A Multifunctional Protein Involved in Protection against Atherosclerosis and Diabetes. Cells. 2019;8(4):319.PubMedPubMedCentralCrossRef
11.
go back to reference Alloubani A, Nimer R, Samara R. Relationship between Hyperlipidemia, Cardiovascular Disease and Stroke: A Systematic Review. Curr Cardiol Rev. 2021;17(6):e051121189015.PubMedPubMedCentralCrossRef Alloubani A, Nimer R, Samara R. Relationship between Hyperlipidemia, Cardiovascular Disease and Stroke: A Systematic Review. Curr Cardiol Rev. 2021;17(6):e051121189015.PubMedPubMedCentralCrossRef
14.
go back to reference Koutnikova H, Genser B, Monteiro-Sepulveda M, et al. Impact of bacterial probiotics on obesity, diabetes and non-alcoholic fatty liver disease related variables: a systematic review and meta-analysis of randomised controlled trials. BMJ Open. 2019;9(3):e017995.PubMedPubMedCentralCrossRef Koutnikova H, Genser B, Monteiro-Sepulveda M, et al. Impact of bacterial probiotics on obesity, diabetes and non-alcoholic fatty liver disease related variables: a systematic review and meta-analysis of randomised controlled trials. BMJ Open. 2019;9(3):e017995.PubMedPubMedCentralCrossRef
15.
go back to reference Pérez-Matute P, Íñiguez M, de Toro M, et al. Autologous fecal transplantation from a lean state potentiates caloric restriction effects on body weight and adiposity in obese mice. Sci Rep. 2020;10(1):9388.ADSPubMedPubMedCentralCrossRef Pérez-Matute P, Íñiguez M, de Toro M, et al. Autologous fecal transplantation from a lean state potentiates caloric restriction effects on body weight and adiposity in obese mice. Sci Rep. 2020;10(1):9388.ADSPubMedPubMedCentralCrossRef
16.
go back to reference Langgartner D, Vaihinger CA, Haffner-Luntzer M, et al. The Role of the Intestinal Microbiome in Chronic Psychosocial Stress-Induced Pathologies in Male Mice. Front Behav Neurosci. 2018;12:252.PubMedPubMedCentralCrossRef Langgartner D, Vaihinger CA, Haffner-Luntzer M, et al. The Role of the Intestinal Microbiome in Chronic Psychosocial Stress-Induced Pathologies in Male Mice. Front Behav Neurosci. 2018;12:252.PubMedPubMedCentralCrossRef
17.
go back to reference Wang H, Lu Y, Yan Y, et al. Promising Treatment for Type 2 Diabetes: Fecal Microbiota Transplantation Reverses Insulin Resistance and Impaired Islets. Front Cell Infect Microbiol. 2019;9:455.PubMedCrossRef Wang H, Lu Y, Yan Y, et al. Promising Treatment for Type 2 Diabetes: Fecal Microbiota Transplantation Reverses Insulin Resistance and Impaired Islets. Front Cell Infect Microbiol. 2019;9:455.PubMedCrossRef
18.
go back to reference Emoto T, Yamashita T, Sasaki N, et al. Analysis of Gut Microbiota in Coronary Artery Disease Patients: a Possible Link between Gut Microbiota and Coronary Artery Disease. J Atheroscler Thromb. 2016;23(8):908–21.PubMedPubMedCentralCrossRef Emoto T, Yamashita T, Sasaki N, et al. Analysis of Gut Microbiota in Coronary Artery Disease Patients: a Possible Link between Gut Microbiota and Coronary Artery Disease. J Atheroscler Thromb. 2016;23(8):908–21.PubMedPubMedCentralCrossRef
19.
go back to reference Wan X, Li T, Liu D, et al. Effect of Marine Microalga Chlorella pyrenoidosa Ethanol Extract on Lipid Metabolism and Gut Microbiota Composition in High-Fat Diet-Fed Rats. Mar Drugs. 2018;16(12):498.PubMedPubMedCentralCrossRef Wan X, Li T, Liu D, et al. Effect of Marine Microalga Chlorella pyrenoidosa Ethanol Extract on Lipid Metabolism and Gut Microbiota Composition in High-Fat Diet-Fed Rats. Mar Drugs. 2018;16(12):498.PubMedPubMedCentralCrossRef
20.
go back to reference Miyajima Y, Karashima S, Ogai K, et al. Impact of gut microbiome on dyslipidemia in japanese adults: Assessment of the Shika-machi super preventive health examination results for causal inference. Front Cell Infect Microbiol. 2022;12: 908997.PubMedPubMedCentralCrossRef Miyajima Y, Karashima S, Ogai K, et al. Impact of gut microbiome on dyslipidemia in japanese adults: Assessment of the Shika-machi super preventive health examination results for causal inference. Front Cell Infect Microbiol. 2022;12: 908997.PubMedPubMedCentralCrossRef
21.
22.
go back to reference Smith GD, Ebrahim S. “Mendelian randomization”: can genetic epidemiology contribute to understanding environmental determinants of disease? Int J Epidemiol. 2003;32(1):1–22.PubMedCrossRef Smith GD, Ebrahim S. “Mendelian randomization”: can genetic epidemiology contribute to understanding environmental determinants of disease? Int J Epidemiol. 2003;32(1):1–22.PubMedCrossRef
23.
go back to reference Smith GD, Lawlor DA, Harbord R, et al. Clustered environments and randomized genes: a fundamental distinction between conventional and genetic epidemiology. PLoS Med. 2007;4(12):e352.PubMedPubMedCentralCrossRef Smith GD, Lawlor DA, Harbord R, et al. Clustered environments and randomized genes: a fundamental distinction between conventional and genetic epidemiology. PLoS Med. 2007;4(12):e352.PubMedPubMedCentralCrossRef
24.
go back to reference Kurilshikov A, Medina-Gomez C, Bacigalupe R, et al. Large-scale association analyses identify host factors influencing human gut microbiome composition. Nat Genet. 2021;53(2):156–65.PubMedPubMedCentralCrossRef Kurilshikov A, Medina-Gomez C, Bacigalupe R, et al. Large-scale association analyses identify host factors influencing human gut microbiome composition. Nat Genet. 2021;53(2):156–65.PubMedPubMedCentralCrossRef
25.
go back to reference Richardson TG, Sanderson E, Palmer TM, et al. Evaluating the relationship between circulating lipoprotein lipids and apolipoproteins with risk of coronary heart disease: A multivariable Mendelian randomisation analysis. PLoS Med. 2020;17(3):e1003062.PubMedPubMedCentralCrossRef Richardson TG, Sanderson E, Palmer TM, et al. Evaluating the relationship between circulating lipoprotein lipids and apolipoproteins with risk of coronary heart disease: A multivariable Mendelian randomisation analysis. PLoS Med. 2020;17(3):e1003062.PubMedPubMedCentralCrossRef
26.
go back to reference Sanna S, van Zuydam NR, Mahajan A, et al. Causal relationships among the gut microbiome, short-chain fatty acids and metabolic diseases. Nat Genet. 2019;51(4):600–5.PubMedPubMedCentralCrossRef Sanna S, van Zuydam NR, Mahajan A, et al. Causal relationships among the gut microbiome, short-chain fatty acids and metabolic diseases. Nat Genet. 2019;51(4):600–5.PubMedPubMedCentralCrossRef
27.
go back to reference Abecasis GR, Auton A, Brooks LD, et al. An integrated map of genetic variation from 1,092 human genomes. Nature. 2012;491(7422):56–65.ADSPubMedCrossRef Abecasis GR, Auton A, Brooks LD, et al. An integrated map of genetic variation from 1,092 human genomes. Nature. 2012;491(7422):56–65.ADSPubMedCrossRef
28.
go back to reference Burgess S, Thompson SG. Avoiding bias from weak instruments in Mendelian randomization studies. Int J Epidemiol. 2011;40(3):755–64.PubMedCrossRef Burgess S, Thompson SG. Avoiding bias from weak instruments in Mendelian randomization studies. Int J Epidemiol. 2011;40(3):755–64.PubMedCrossRef
29.
30.
go back to reference Burgess S, Butterworth A, Thompson SG. Mendelian randomization analysis with multiple genetic variants using summarized data. Genet Epidemiol. 2013;37(7):658–65.PubMedPubMedCentralCrossRef Burgess S, Butterworth A, Thompson SG. Mendelian randomization analysis with multiple genetic variants using summarized data. Genet Epidemiol. 2013;37(7):658–65.PubMedPubMedCentralCrossRef
31.
go back to reference Bowden J, Davey Smith G, Burgess S. Mendelian randomization with invalid instruments: effect estimation and bias detection through Egger regression. Int J Epidemiol. 2015;44(2):512–25.PubMedPubMedCentralCrossRef Bowden J, Davey Smith G, Burgess S. Mendelian randomization with invalid instruments: effect estimation and bias detection through Egger regression. Int J Epidemiol. 2015;44(2):512–25.PubMedPubMedCentralCrossRef
32.
go back to reference Hartwig FP, Davey Smith G, Bowden J. Robust inference in summary data Mendelian randomization via the zero modal pleiotropy assumption. Int J Epidemiol. 2017;46(6):1985–98.PubMedPubMedCentralCrossRef Hartwig FP, Davey Smith G, Bowden J. Robust inference in summary data Mendelian randomization via the zero modal pleiotropy assumption. Int J Epidemiol. 2017;46(6):1985–98.PubMedPubMedCentralCrossRef
33.
go back to reference Burgess S, Dudbridge F, Thompson SG. Combining information on multiple instrumental variables in Mendelian randomization: comparison of allele score and summarized data methods. Stat Med. 2016;35(11):1880–906.MathSciNetPubMedCrossRef Burgess S, Dudbridge F, Thompson SG. Combining information on multiple instrumental variables in Mendelian randomization: comparison of allele score and summarized data methods. Stat Med. 2016;35(11):1880–906.MathSciNetPubMedCrossRef
34.
go back to reference Bowden J, Davey Smith G, Haycock PC, et al. Consistent Estimation in Mendelian Randomization with Some Invalid Instruments Using a Weighted Median Estimator. Genet Epidemiol. 2016;40(4):304–14.PubMedPubMedCentralCrossRef Bowden J, Davey Smith G, Haycock PC, et al. Consistent Estimation in Mendelian Randomization with Some Invalid Instruments Using a Weighted Median Estimator. Genet Epidemiol. 2016;40(4):304–14.PubMedPubMedCentralCrossRef
35.
go back to reference Ni JJ, Xu Q, Yan SS, et al. Gut Microbiota and Psychiatric Disorders: A Two-Sample Mendelian Randomization Study. Front Microbiol. 2021;12: 737197.PubMedCrossRef Ni JJ, Xu Q, Yan SS, et al. Gut Microbiota and Psychiatric Disorders: A Two-Sample Mendelian Randomization Study. Front Microbiol. 2021;12: 737197.PubMedCrossRef
36.
go back to reference Burgess S. Sample size and power calculations in Mendelian randomization with a single instrumental variable and a binary outcome. Int J Epidemiol. 2014;43(3):922–9.PubMedPubMedCentralCrossRef Burgess S. Sample size and power calculations in Mendelian randomization with a single instrumental variable and a binary outcome. Int J Epidemiol. 2014;43(3):922–9.PubMedPubMedCentralCrossRef
37.
38.
go back to reference Verbanck M, Chen CY, Neale B, et al. Detection of widespread horizontal pleiotropy in causal relationships inferred from Mendelian randomization between complex traits and diseases. Nat Genet. 2018;50(5):693–8.PubMedPubMedCentralCrossRef Verbanck M, Chen CY, Neale B, et al. Detection of widespread horizontal pleiotropy in causal relationships inferred from Mendelian randomization between complex traits and diseases. Nat Genet. 2018;50(5):693–8.PubMedPubMedCentralCrossRef
39.
42.
go back to reference Fan L, Ren J, Chen Y, et al. Effect of fecal microbiota transplantation on primary hypertension and the underlying mechanism of gut microbiome restoration: protocol of a randomized, blinded, placebo-controlled study. Trials. 2022;23(1):178.PubMedPubMedCentralCrossRef Fan L, Ren J, Chen Y, et al. Effect of fecal microbiota transplantation on primary hypertension and the underlying mechanism of gut microbiome restoration: protocol of a randomized, blinded, placebo-controlled study. Trials. 2022;23(1):178.PubMedPubMedCentralCrossRef
43.
go back to reference Li Z, Lai J, Zhang P, et al. Multi-omics analyses of serum metabolome, gut microbiome and brain function reveal dysregulated microbiota-gut-brain axis in bipolar depression. Mol Psychiatry. 2022;27(10):4123–35.PubMedCrossRef Li Z, Lai J, Zhang P, et al. Multi-omics analyses of serum metabolome, gut microbiome and brain function reveal dysregulated microbiota-gut-brain axis in bipolar depression. Mol Psychiatry. 2022;27(10):4123–35.PubMedCrossRef
44.
45.
go back to reference Rothschild D, Weissbrod O, Barkan E, et al. Environment dominates over host genetics in shaping human gut microbiota. Nature. 2018;555(7695):210–5.ADSPubMedCrossRef Rothschild D, Weissbrod O, Barkan E, et al. Environment dominates over host genetics in shaping human gut microbiota. Nature. 2018;555(7695):210–5.ADSPubMedCrossRef
46.
go back to reference Liu B, Ye D, Yang H, et al. Two-Sample Mendelian Randomization Analysis Investigates Causal Associations Between Gut Microbial Genera and Inflammatory Bowel Disease, and Specificity Causal Associations in Ulcerative Colitis or Crohn’s Disease. Front Immunol. 2022;13: 921546.PubMedPubMedCentralCrossRef Liu B, Ye D, Yang H, et al. Two-Sample Mendelian Randomization Analysis Investigates Causal Associations Between Gut Microbial Genera and Inflammatory Bowel Disease, and Specificity Causal Associations in Ulcerative Colitis or Crohn’s Disease. Front Immunol. 2022;13: 921546.PubMedPubMedCentralCrossRef
47.
go back to reference Hatcher C, Richenberg G, Waterson S, et al. Application of Mendelian randomization to explore the causal role of the human gut microbiome in colorectal cancer. Sci Rep. 2023;13(1):5968.ADSPubMedPubMedCentralCrossRef Hatcher C, Richenberg G, Waterson S, et al. Application of Mendelian randomization to explore the causal role of the human gut microbiome in colorectal cancer. Sci Rep. 2023;13(1):5968.ADSPubMedPubMedCentralCrossRef
48.
go back to reference Nava GM, Carbonero F, Croix JA, et al. Abundance and diversity of mucosa-associated hydrogenotrophic microbes in the healthy human colon. Isme j. 2012;6(1):57–70.PubMedCrossRef Nava GM, Carbonero F, Croix JA, et al. Abundance and diversity of mucosa-associated hydrogenotrophic microbes in the healthy human colon. Isme j. 2012;6(1):57–70.PubMedCrossRef
49.
go back to reference Earley H, Lennon G, Balfe A, et al. A Preliminary Study Examining the Binding Capacity of Akkermansia muciniphila and Desulfovibrio spp., to Colonic Mucin in Health and Ulcerative Colitis. PLoS One. 2015;10(10):e0135280.PubMedPubMedCentralCrossRef Earley H, Lennon G, Balfe A, et al. A Preliminary Study Examining the Binding Capacity of Akkermansia muciniphila and Desulfovibrio spp., to Colonic Mucin in Health and Ulcerative Colitis. PLoS One. 2015;10(10):e0135280.PubMedPubMedCentralCrossRef
50.
go back to reference Karlsson CL, Onnerfält J, Xu J, et al. The microbiota of the gut in preschool children with normal and excessive body weight. Obesity (Silver Spring). 2012;20(11):2257–61.PubMedCrossRef Karlsson CL, Onnerfält J, Xu J, et al. The microbiota of the gut in preschool children with normal and excessive body weight. Obesity (Silver Spring). 2012;20(11):2257–61.PubMedCrossRef
51.
go back to reference Andoh A, Nishida A, Takahashi K, et al. Comparison of the gut microbial community between obese and lean peoples using 16S gene sequencing in a Japanese population. J Clin Biochem Nutr. 2016;59(1):65–70.PubMedPubMedCentralCrossRef Andoh A, Nishida A, Takahashi K, et al. Comparison of the gut microbial community between obese and lean peoples using 16S gene sequencing in a Japanese population. J Clin Biochem Nutr. 2016;59(1):65–70.PubMedPubMedCentralCrossRef
52.
go back to reference Carbonero F, Benefiel AC, Alizadeh-Ghamsari AH, et al. Microbial pathways in colonic sulfur metabolism and links with health and disease. Front Physiol. 2012;3:448.PubMedPubMedCentralCrossRef Carbonero F, Benefiel AC, Alizadeh-Ghamsari AH, et al. Microbial pathways in colonic sulfur metabolism and links with health and disease. Front Physiol. 2012;3:448.PubMedPubMedCentralCrossRef
53.
go back to reference Meng G, Zhao S, Xie L, et al. Protein S-sulfhydration by hydrogen sulfide in cardiovascular system. Br J Pharmacol. 2018;175(8):1146–56.PubMedCrossRef Meng G, Zhao S, Xie L, et al. Protein S-sulfhydration by hydrogen sulfide in cardiovascular system. Br J Pharmacol. 2018;175(8):1146–56.PubMedCrossRef
54.
go back to reference Carter RN, Morton NM. Cysteine and hydrogen sulphide in the regulation of metabolism: insights from genetics and pharmacology. J Pathol. 2016;238(2):321–32.PubMedCrossRef Carter RN, Morton NM. Cysteine and hydrogen sulphide in the regulation of metabolism: insights from genetics and pharmacology. J Pathol. 2016;238(2):321–32.PubMedCrossRef
55.
go back to reference Mani S, Li H, Untereiner A, et al. Decreased endogenous production of hydrogen sulfide accelerates atherosclerosis. Circulation. 2013;127(25):2523–34.PubMedCrossRef Mani S, Li H, Untereiner A, et al. Decreased endogenous production of hydrogen sulfide accelerates atherosclerosis. Circulation. 2013;127(25):2523–34.PubMedCrossRef
56.
go back to reference Xu S, Liu Z, Liu P. Targeting hydrogen sulfide as a promising therapeutic strategy for atherosclerosis. Int J Cardiol. 2014;172(2):313–7.PubMedCrossRef Xu S, Liu Z, Liu P. Targeting hydrogen sulfide as a promising therapeutic strategy for atherosclerosis. Int J Cardiol. 2014;172(2):313–7.PubMedCrossRef
57.
go back to reference Hong Y, Li B, Zheng N, et al. Integrated Metagenomic and Metabolomic Analyses of the Effect of Astragalus Polysaccharides on Alleviating High-Fat Diet-Induced Metabolic Disorders. Front Pharmacol. 2020;11:833.PubMedPubMedCentralCrossRef Hong Y, Li B, Zheng N, et al. Integrated Metagenomic and Metabolomic Analyses of the Effect of Astragalus Polysaccharides on Alleviating High-Fat Diet-Induced Metabolic Disorders. Front Pharmacol. 2020;11:833.PubMedPubMedCentralCrossRef
58.
go back to reference Hong Y, Sheng L, Zhong J, et al. Desulfovibrio vulgaris, a potent acetic acid-producing bacterium, attenuates nonalcoholic fatty liver disease in mice. Gut Microbes. 2021;13(1):1–20.PubMedCrossRef Hong Y, Sheng L, Zhong J, et al. Desulfovibrio vulgaris, a potent acetic acid-producing bacterium, attenuates nonalcoholic fatty liver disease in mice. Gut Microbes. 2021;13(1):1–20.PubMedCrossRef
59.
go back to reference Li L, He M, Xiao H, et al. Acetic Acid Influences BRL-3A Cell Lipid Metabolism via the AMPK Signalling Pathway. Cell Physiol Biochem. 2018;45(5):2021–30.PubMedCrossRef Li L, He M, Xiao H, et al. Acetic Acid Influences BRL-3A Cell Lipid Metabolism via the AMPK Signalling Pathway. Cell Physiol Biochem. 2018;45(5):2021–30.PubMedCrossRef
60.
go back to reference Li X, Chen H, Guan Y, et al. Acetic acid activates the AMP-activated protein kinase signaling pathway to regulate lipid metabolism in bovine hepatocytes. PLoS One. 2013;8(7):e67880.ADSPubMedPubMedCentralCrossRef Li X, Chen H, Guan Y, et al. Acetic acid activates the AMP-activated protein kinase signaling pathway to regulate lipid metabolism in bovine hepatocytes. PLoS One. 2013;8(7):e67880.ADSPubMedPubMedCentralCrossRef
61.
go back to reference Duncan SH, Barcenilla A, Stewart CS, et al. Acetate utilization and butyryl coenzyme A (CoA):acetate-CoA transferase in butyrate-producing bacteria from the human large intestine. Appl Environ Microbiol. 2002;68(10):5186–90.ADSPubMedPubMedCentralCrossRef Duncan SH, Barcenilla A, Stewart CS, et al. Acetate utilization and butyryl coenzyme A (CoA):acetate-CoA transferase in butyrate-producing bacteria from the human large intestine. Appl Environ Microbiol. 2002;68(10):5186–90.ADSPubMedPubMedCentralCrossRef
62.
go back to reference Hiippala K, Jouhten H, Ronkainen A, et al. The Potential of Gut Commensals in Reinforcing Intestinal Barrier Function and Alleviating Inflammation. Nutrients. 2018;10(8):988.PubMedPubMedCentralCrossRef Hiippala K, Jouhten H, Ronkainen A, et al. The Potential of Gut Commensals in Reinforcing Intestinal Barrier Function and Alleviating Inflammation. Nutrients. 2018;10(8):988.PubMedPubMedCentralCrossRef
63.
go back to reference Li W, Zhu Y, Li Y, et al. The gut microbiota of hand, foot and mouth disease patients demonstrates down-regulated butyrate-producing bacteria and up-regulated inflammation-inducing bacteria. Acta Paediatr. 2019;108(6):1133–9.PubMedCrossRef Li W, Zhu Y, Li Y, et al. The gut microbiota of hand, foot and mouth disease patients demonstrates down-regulated butyrate-producing bacteria and up-regulated inflammation-inducing bacteria. Acta Paediatr. 2019;108(6):1133–9.PubMedCrossRef
64.
go back to reference Plovier H, Everard A, Druart C, et al. A purified membrane protein from Akkermansia muciniphila or the pasteurized bacterium improves metabolism in obese and diabetic mice. Nat Med. 2017;23(1):107–13.PubMedCrossRef Plovier H, Everard A, Druart C, et al. A purified membrane protein from Akkermansia muciniphila or the pasteurized bacterium improves metabolism in obese and diabetic mice. Nat Med. 2017;23(1):107–13.PubMedCrossRef
65.
66.
go back to reference Gophna U, Konikoff T, Nielsen HB. Oscillospira and related bacteria - From metagenomic species to metabolic features. Environ Microbiol. 2017;19(3):835–41.PubMedCrossRef Gophna U, Konikoff T, Nielsen HB. Oscillospira and related bacteria - From metagenomic species to metabolic features. Environ Microbiol. 2017;19(3):835–41.PubMedCrossRef
67.
go back to reference Arora T, Bäckhed F. The gut microbiota and metabolic disease: current understanding and future perspectives. J Intern Med. 2016;280(4):339–49.PubMedCrossRef Arora T, Bäckhed F. The gut microbiota and metabolic disease: current understanding and future perspectives. J Intern Med. 2016;280(4):339–49.PubMedCrossRef
68.
69.
go back to reference Khan S, Jena G. Sodium butyrate reduces insulin-resistance, fat accumulation and dyslipidemia in type-2 diabetic rat: A comparative study with metformin. Chem Biol Interact. 2016;254:124–34.PubMedCrossRef Khan S, Jena G. Sodium butyrate reduces insulin-resistance, fat accumulation and dyslipidemia in type-2 diabetic rat: A comparative study with metformin. Chem Biol Interact. 2016;254:124–34.PubMedCrossRef
70.
go back to reference Mollica MP, Mattace Raso G, Cavaliere G, et al. Butyrate Regulates Liver Mitochondrial Function, Efficiency, and Dynamics in Insulin-Resistant Obese Mice. Diabetes. 2017;66(5):1405–18.PubMedCrossRef Mollica MP, Mattace Raso G, Cavaliere G, et al. Butyrate Regulates Liver Mitochondrial Function, Efficiency, and Dynamics in Insulin-Resistant Obese Mice. Diabetes. 2017;66(5):1405–18.PubMedCrossRef
71.
go back to reference Bridgeman SC, Northrop W, Melton PE, et al. Butyrate generated by gut microbiota and its therapeutic role in metabolic syndrome. Pharmacol Res. 2020;160: 105174.PubMedCrossRef Bridgeman SC, Northrop W, Melton PE, et al. Butyrate generated by gut microbiota and its therapeutic role in metabolic syndrome. Pharmacol Res. 2020;160: 105174.PubMedCrossRef
72.
73.
go back to reference Hara T, Kimura I, Inoue D, et al. Free fatty acid receptors and their role in regulation of energy metabolism. Rev Physiol Biochem Pharmacol. 2013;164:77–116.PubMedCrossRef Hara T, Kimura I, Inoue D, et al. Free fatty acid receptors and their role in regulation of energy metabolism. Rev Physiol Biochem Pharmacol. 2013;164:77–116.PubMedCrossRef
74.
go back to reference Ichimura A, Hasegawa S, Kasubuchi M, et al. Free fatty acid receptors as therapeutic targets for the treatment of diabetes. Front Pharmacol. 2014;5:236.PubMedPubMedCentralCrossRef Ichimura A, Hasegawa S, Kasubuchi M, et al. Free fatty acid receptors as therapeutic targets for the treatment of diabetes. Front Pharmacol. 2014;5:236.PubMedPubMedCentralCrossRef
75.
go back to reference Henneke L, Schlicht K, Andreani NA, et al. A dietary carbohydrate - gut Parasutterella - human fatty acid biosynthesis metabolic axis in obesity and type 2 diabetes. Gut Microbes. 2022;14(1):2057778.PubMedPubMedCentralCrossRef Henneke L, Schlicht K, Andreani NA, et al. A dietary carbohydrate - gut Parasutterella - human fatty acid biosynthesis metabolic axis in obesity and type 2 diabetes. Gut Microbes. 2022;14(1):2057778.PubMedPubMedCentralCrossRef
76.
go back to reference Gu Y, Liu C, Zheng N, et al. Metabolic and Gut Microbial Characterization of Obesity-Prone Mice under a High-Fat Diet. J Proteome Res. 2019;18(4):1703–14.PubMedCrossRef Gu Y, Liu C, Zheng N, et al. Metabolic and Gut Microbial Characterization of Obesity-Prone Mice under a High-Fat Diet. J Proteome Res. 2019;18(4):1703–14.PubMedCrossRef
77.
go back to reference Lee SH, You HS, Kang HG, et al. Association between Altered Blood Parameters and Gut Microbiota after Synbiotic Intake in Healthy, Elderly Korean Women. Nutrients. 2020;12(10):3112.PubMedPubMedCentralCrossRef Lee SH, You HS, Kang HG, et al. Association between Altered Blood Parameters and Gut Microbiota after Synbiotic Intake in Healthy, Elderly Korean Women. Nutrients. 2020;12(10):3112.PubMedPubMedCentralCrossRef
78.
go back to reference Kim HJ, Jeong S, Oh YH, et al. Changes in high-density lipoprotein cholesterol with risk of Cardiovascular Disease among initially high-density lipoprotein-high participants. Cardiovasc Diabetol. 2023;22(1):71.PubMedPubMedCentralCrossRef Kim HJ, Jeong S, Oh YH, et al. Changes in high-density lipoprotein cholesterol with risk of Cardiovascular Disease among initially high-density lipoprotein-high participants. Cardiovasc Diabetol. 2023;22(1):71.PubMedPubMedCentralCrossRef
79.
go back to reference Zhu T, Wang Z, He J, et al. D-galactose protects the intestine from ionizing radiation-induced injury by altering the gut microbiome. J Radiat Res. 2022;63(6):805–16.PubMedPubMedCentralCrossRef Zhu T, Wang Z, He J, et al. D-galactose protects the intestine from ionizing radiation-induced injury by altering the gut microbiome. J Radiat Res. 2022;63(6):805–16.PubMedPubMedCentralCrossRef
80.
go back to reference Schwiertz A, Taras D, Schäfer K, et al. Microbiota and SCFA in lean and overweight healthy subjects. Obesity (Silver Spring). 2010;18(1):190–5.PubMedCrossRef Schwiertz A, Taras D, Schäfer K, et al. Microbiota and SCFA in lean and overweight healthy subjects. Obesity (Silver Spring). 2010;18(1):190–5.PubMedCrossRef
81.
go back to reference López-Montoya P, Cerqueda-García D, Rodríguez-Flores M, et al. Association of Gut Microbiota with Atherogenic Dyslipidemia, and Its Impact on Serum Lipid Levels after Bariatric Surgery. Nutrients. 2022;14(17):3545.PubMedPubMedCentralCrossRef López-Montoya P, Cerqueda-García D, Rodríguez-Flores M, et al. Association of Gut Microbiota with Atherogenic Dyslipidemia, and Its Impact on Serum Lipid Levels after Bariatric Surgery. Nutrients. 2022;14(17):3545.PubMedPubMedCentralCrossRef
82.
go back to reference Parks DH, Chuvochina M, Waite DW, et al. A standardized bacterial taxonomy based on genome phylogeny substantially revises the tree of life. Nat Biotechnol. 2018;36(10):996–1004.PubMedCrossRef Parks DH, Chuvochina M, Waite DW, et al. A standardized bacterial taxonomy based on genome phylogeny substantially revises the tree of life. Nat Biotechnol. 2018;36(10):996–1004.PubMedCrossRef
83.
go back to reference Fu J, Bonder MJ, Cenit MC, et al. The Gut Microbiome Contributes to a Substantial Proportion of the Variation in Blood Lipids. Circ Res. 2015;117(9):817–24.PubMedPubMedCentralCrossRef Fu J, Bonder MJ, Cenit MC, et al. The Gut Microbiome Contributes to a Substantial Proportion of the Variation in Blood Lipids. Circ Res. 2015;117(9):817–24.PubMedPubMedCentralCrossRef
84.
go back to reference He Y, Wu W, Wu S, et al. Linking gut microbiota, metabolic syndrome and economic status based on a population-level analysis. Microbiome. 2018;6(1):172.PubMedPubMedCentralCrossRef He Y, Wu W, Wu S, et al. Linking gut microbiota, metabolic syndrome and economic status based on a population-level analysis. Microbiome. 2018;6(1):172.PubMedPubMedCentralCrossRef
85.
go back to reference Rodrigues AC, Sobrino B, Genvigir FD, et al. Genetic variants in genes related to lipid metabolism and atherosclerosis, dyslipidemia and atorvastatin response. Clin Chim Acta. 2013;417:8–11.PubMedCrossRef Rodrigues AC, Sobrino B, Genvigir FD, et al. Genetic variants in genes related to lipid metabolism and atherosclerosis, dyslipidemia and atorvastatin response. Clin Chim Acta. 2013;417:8–11.PubMedCrossRef
Metadata
Title
Causality of the gut microbiome and atherosclerosis-related lipids: a bidirectional Mendelian Randomization study
Authors
Da Teng
Wenjuan Jia
Wenlong Wang
Lanlan Liao
Bowen Xu
Lei Gong
Haibin Dong
Lin Zhong
Jun Yang
Publication date
01-12-2024
Publisher
BioMed Central
Published in
BMC Cardiovascular Disorders / Issue 1/2024
Electronic ISSN: 1471-2261
DOI
https://doi.org/10.1186/s12872-024-03804-3

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