{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T15:15:57Z","timestamp":1786720557177,"version":"build-2736575974"},"reference-count":43,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,3,5]],"date-time":"2024-03-05T00:00:00Z","timestamp":1709596800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>The relationship between gut microbiota and peripheral artery disease (PAD) remains understudied. While traditional risk factors like smoking and hyperlipidemia are well-understood, our study aims to determine the potential causative association of gut microbiota with PAD using Mendelian Randomization.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Data from the International MiBioGen Consortium and the FinnGen research project were used to study 211 bacterial taxa. Instrumental variables, comprising 2079 SNPs, were selected based on significance levels and linkage disequilibrium. Analyses were conducted utilizing the inverse-variance weighted (IVW) method and other statistical MR techniques to mitigate biases, processed in R (v4.3.1) with the TwosampleMR package.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Three bacterial taxa, namely genus <jats:italic>Coprococcus2<\/jats:italic>, <jats:italic>RuminococcaceaeUCG004<\/jats:italic>, and <jats:italic>RuminococcaceaeUCG010<\/jats:italic>, emerged as protective factors against PAD. In contrast, family. FamilyXI and the genus <jats:italic>Lachnoclostridium<\/jats:italic> and <jats:italic>LachnospiraceaeUCG001<\/jats:italic> were identified as risk factors.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our findings hint at a causative association between certain gut microbiota and PAD, introducing new avenues for understanding PAD\u2019s etiology and developing effective treatments. The observed associations now warrant further validation in varied populations and detailed exploration at finer taxonomic levels.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fmicb.2024.1340262","type":"journal-article","created":{"date-parts":[[2024,3,5]],"date-time":"2024-03-05T05:08:10Z","timestamp":1709615290000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":8,"title":["Gut microbiota\u2019s causative relationship with peripheral artery disease: a Mendelian randomization study"],"prefix":"10.3389","volume":"15","author":[{"given":"Yu","family":"Tian","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guanqun","family":"Yao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Loren","family":"Skudder-Hill","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guangyang","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuxuan","family":"Qian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qianhui","family":"Bao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,3,5]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"108991","DOI":"10.1016\/j.jnutbio.2022.108991","article-title":"Interplay between diet, the gut microbiome, and atherosclerosis: role of dysbiosis and microbial metabolites on inflammation and disordered lipid metabolism","volume":"105","author":"Anto","year":"2022","journal-title":"J. Nutr. Biochem."},{"key":"ref2","doi-asserted-by":"publisher","first-page":"586","DOI":"10.1016\/j.atherosclerosis.2010.09.010","article-title":"Mean platelet volume and prevalence of peripheral artery disease, the National Health and nutrition examination survey, 1999\u20132004","volume":"213","author":"Berger","year":"2010","journal-title":"Atherosclerosis"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"512","DOI":"10.1093\/ije\/dyv080","article-title":"Mendelian randomization with invalid instruments: effect estimation and bias detection through egger regression","volume":"44","author":"Bowden","year":"2015","journal-title":"Int. J. Epidemiol."},{"key":"ref4","doi-asserted-by":"publisher","first-page":"304","DOI":"10.1002\/gepi.21965","article-title":"Consistent estimation in Mendelian randomization with some invalid instruments using a weighted median estimator","volume":"40","author":"Bowden","year":"2016","journal-title":"Genet. Epidemiol."},{"key":"ref5","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1038\/s41522-022-00273-4","article-title":"Integrated metagenomics identifies a crucial role for trimethylamine-producing Lachnoclostridium in promoting atherosclerosis","volume":"8","author":"Cai","year":"2022","journal-title":"NPJ Biofilms Microbiomes"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"5959","DOI":"10.1007\/s00253-020-10620-0","article-title":"Lactobacillus plantarum FRT10 alleviated high-fat diet-induced obesity in mice through regulating the PPAR\u03b1 signal pathway and gut microbiota","volume":"104","author":"Cai","year":"2020","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"ref7","doi-asserted-by":"publisher","first-page":"1940","DOI":"10.3390\/ijms24031940","article-title":"Gut microbiota-derived TMAO: a causal factor promoting atherosclerotic cardiovascular disease","volume":"24","author":"Canyelles","year":"2023","journal-title":"Int. J. Mol. Sci."},{"key":"ref8","doi-asserted-by":"publisher","first-page":"106586","DOI":"10.1016\/j.phrs.2022.106586","article-title":"Gut microbiome and metabolites, the future direction of diagnosis and treatment of atherosclerosis","volume":"187","author":"Cao","year":"2023","journal-title":"Pharmacol. Res."},{"key":"ref9","doi-asserted-by":"publisher","first-page":"e0195622","DOI":"10.1128\/spectrum.01956-22","article-title":"Characteristics and correlations of the Oral and gut fungal microbiome with hypertension","volume":"11","author":"Chen","year":"2023","journal-title":"Microbiol. Spectr."},{"key":"ref10","doi-asserted-by":"publisher","first-page":"2269","DOI":"10.1097\/CM9.0000000000002206","article-title":"Gut microbiota and microbiota-derived metabolites in cardiovascular diseases","volume":"136","author":"Chen","year":"2023","journal-title":"Chin. Med. J."},{"key":"ref11","doi-asserted-by":"publisher","first-page":"e171","DOI":"10.1161\/CIR.0000000000001005","article-title":"Lower extremity peripheral artery disease: contemporary epidemiology, management gaps, and future directions: a scientific statement from the American Heart Association","volume":"144","author":"Criqui","year":"2021","journal-title":"Circulation"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"1329","DOI":"10.1016\/S0140-6736(13)61249-0","article-title":"Comparison of global estimates of prevalence and risk factors for peripheral artery disease in 2000 and 2010: a systematic review and analysis","volume":"382","author":"Fowkes","year":"2013","journal-title":"Lancet"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1186\/s40168-022-01436-3","article-title":"Gut microbiota in a mouse model of obesity and peripheral neuropathy associated with plasma and nerve lipidomics and nerve transcriptomics","volume":"11","author":"Guo","year":"2023","journal-title":"Microbiome"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"1985","DOI":"10.1093\/ije\/dyx102","article-title":"Robust inference in summary data Mendelian randomization via the zero modal pleiotropy assumption","volume":"46","author":"Hartwig","year":"2017","journal-title":"Int. J. Epidemiol."},{"key":"ref15","doi-asserted-by":"publisher","first-page":"121947","DOI":"10.1016\/j.lfs.2023.121947","article-title":"Importance of gut microbiota metabolites in the development of cardiovascular diseases (CVD)","volume":"329","author":"Hemmati","year":"2023","journal-title":"Life Sci."},{"key":"ref16","doi-asserted-by":"publisher","first-page":"666","DOI":"10.1093\/aje\/153.7.666","article-title":"Incidence of and risk factors for asymptomatic peripheral arterial occlusive disease: a longitudinal study","volume":"153","author":"Hooi","year":"2001","journal-title":"Am. J. Epidemiol."},{"key":"ref17","doi-asserted-by":"publisher","first-page":"581","DOI":"10.1007\/s12265-022-10330-0","article-title":"The role of gut microbiota and trimethylamine N-oxide in cardiovascular diseases","volume":"16","author":"Huang","year":"2023","journal-title":"J. Cardiovasc. Transl. Res."},{"key":"ref18","doi-asserted-by":"publisher","first-page":"1238","DOI":"10.3390\/microorganisms8081238","article-title":"Impact of Cyanidin-3-glucoside on gut microbiota and relationship with metabolism and inflammation in high fat-high sucrose diet-induced insulin resistant mice","volume":"8","author":"Huang","year":"2020","journal-title":"Microorganisms"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"645212","DOI":"10.3389\/fphys.2021.645212","article-title":"Exploration of crucial mediators for carotid atherosclerosis pathogenesis through integration of microbiome, metabolome, and transcriptome","volume":"12","author":"Ji","year":"2021","journal-title":"Front. Physiol."},{"key":"ref20","doi-asserted-by":"publisher","first-page":"4851","DOI":"10.1093\/bioinformatics\/btz469","article-title":"PhenoScanner V2: an expanded tool for searching human genotype-phenotype associations","volume":"35","author":"Kamat","year":"2019","journal-title":"Bioinformatics"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"156","DOI":"10.1038\/s41588-020-00763-1","article-title":"Large-scale association analyses identify host factors influencing human gut microbiome composition","volume":"53","author":"Kurilshikov","year":"2021","journal-title":"Nat. Genet."},{"key":"ref22","doi-asserted-by":"publisher","first-page":"508","DOI":"10.1038\/s41586-022-05473-8","article-title":"FinnGen provides genetic insights from a well-phenotyped isolated population","volume":"613","author":"Kurki","year":"2023","journal-title":"Nature"},{"key":"ref23","doi-asserted-by":"publisher","first-page":"264","DOI":"10.1007\/s13679-023-00510-7","article-title":"Obesity and peripheral artery disease: current evidence and controversies","volume":"12","author":"Lempesis","year":"2023","journal-title":"Curr. Obes. Rep."},{"key":"ref24","doi-asserted-by":"publisher","first-page":"e0105023","DOI":"10.1128\/spectrum.01050-23","article-title":"Structural changes in the gut virome of patients with atherosclerotic cardiovascular disease","volume":"12","author":"Li","year":"2024","journal-title":"Microbiol. Spectr."},{"key":"ref25","doi-asserted-by":"publisher","first-page":"66","DOI":"10.1186\/s12916-023-02761-6","article-title":"Causal relationship between gut microbiota and cancers: a two-sample Mendelian randomisation study","volume":"21","author":"Long","year":"2023","journal-title":"BMC Med."},{"key":"ref26","doi-asserted-by":"publisher","first-page":"1246","DOI":"10.3390\/microorganisms11051246","article-title":"Characteristic gut bacteria in high barley consuming Japanese individuals without hypertension","volume":"11","author":"Maruyama","year":"2023","journal-title":"Microorganisms"},{"key":"ref27","doi-asserted-by":"publisher","first-page":"810","DOI":"10.1016\/j.jchf.2023.03.008","article-title":"Microbially produced imidazole propionate is associated with heart failure and mortality","volume":"11","author":"Molinaro","year":"2023","journal-title":"JACC Heart Fail"},{"key":"ref28","doi-asserted-by":"publisher","first-page":"e0277621","DOI":"10.1128\/spectrum.02776-21","article-title":"Survival strategies and metabolic interactions between Ruminococcus gauvreauii and Ruminococcoides bili","volume":"10","author":"Molinero","year":"2022","journal-title":"Microbiol. Spectr."},{"key":"ref29","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1161\/01.ATV.0000148450.56697.4a","article-title":"Vitamin D, shedding light on the development of disease in peripheral arteries","volume":"25","author":"Norman","year":"2005","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref30","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1161\/CIRCULATIONAHA.110.003954","article-title":"Secondary prevention and mortality in peripheral artery disease: National Health and nutrition examination study, 1999 to 2004","volume":"124","author":"Pande","year":"2011","journal-title":"Circulation"},{"key":"ref31","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1016\/j.gheart.2013.12.008","article-title":"Global and regional burden of death and disability from peripheral artery disease: 21 world regions, 1990 to 2010","volume":"9","author":"Sampson","year":"2014","journal-title":"Glob. Heart"},{"key":"ref32","doi-asserted-by":"publisher","first-page":"504","DOI":"10.3390\/ph16040504","article-title":"Gut-derived metabolite, trimethylamine-N-oxide (TMAO) in cardio-metabolic diseases: detection, mechanism, and potential therapeutics","volume":"16","author":"Shanmugham","year":"2023","journal-title":"Pharmaceuticals"},{"key":"ref33","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1007\/s11883-021-00910-x","article-title":"Trimethylamine N-oxide (TMAO), diet and cardiovascular disease","volume":"23","author":"Thomas","year":"2021","journal-title":"Curr. Atheroscler. Rep."},{"key":"ref34","doi-asserted-by":"publisher","first-page":"573","DOI":"10.3390\/microorganisms8040573","article-title":"The controversial role of human gut Lachnospiraceae","volume":"8","author":"Vacca","year":"2020","journal-title":"Microorganisms"},{"key":"ref35","doi-asserted-by":"publisher","first-page":"693","DOI":"10.1038\/s41588-018-0099-7","article-title":"Detection of widespread horizontal pleiotropy in causal relationships inferred from Mendelian randomization between complex traits and diseases","volume":"50","author":"Verbanck","year":"2018","journal-title":"Nat. Genet."},{"key":"ref36","doi-asserted-by":"publisher","first-page":"553","DOI":"10.1161\/CIRCRESAHA.120.316242","article-title":"Gut microbiota and cardiovascular disease","volume":"127","author":"Witkowski","year":"2020","journal-title":"Circ. Res."},{"key":"ref37","doi-asserted-by":"publisher","first-page":"472","DOI":"10.3390\/medicina58040472","article-title":"Recent advances in the treatment of insulin resistance targeting molecular and metabolic pathways: fighting a losing battle","volume":"58","author":"Wolosowicz","year":"2022","journal-title":"Medicina"},{"key":"ref38","doi-asserted-by":"publisher","first-page":"626","DOI":"10.1016\/j.tjnut.2023.12.019","article-title":"Effects of fermented extracts of Wuniuzao dark loose tea on hepatic sterol regulatory element-binding protein pathway and gut microbiota disorder in obese mice","volume":"154","author":"Ye","year":"2023","journal-title":"J. Nutr."},{"key":"ref39","doi-asserted-by":"publisher","first-page":"1173225","DOI":"10.3389\/fnut.2023.1173225","article-title":"Beneficial effects of seaweed-derived components on metabolic syndrome via gut microbiota modulation","volume":"10","author":"Zang","year":"2023","journal-title":"Front. Nutr."},{"key":"ref40","doi-asserted-by":"publisher","first-page":"113436","DOI":"10.1016\/j.jep.2020.113436","article-title":"Dingxin recipe IV attenuates atherosclerosis by regulating lipid metabolism through LXR-\u03b1\/SREBP1 pathway and modulating the gut microbiota in ApoE\u2212\/\u2212 mice fed with HFD","volume":"266","author":"Zhang","year":"2021","journal-title":"J. Ethnopharmacol."},{"key":"ref41","doi-asserted-by":"publisher","first-page":"212","DOI":"10.1186\/s12964-023-01219-9","article-title":"Short-chain fatty acids in diseases","volume":"21","author":"Zhang","year":"2023","journal-title":"Cell Commun. Signal"},{"key":"ref42","doi-asserted-by":"publisher","first-page":"1193725","DOI":"10.3389\/fmicb.2023.1193725","article-title":"Mendelian randomization analysis revealed a gut microbiota-mammary axis in breast cancer","volume":"14","author":"Zhang","year":"2023","journal-title":"Front. Microbiol."},{"key":"ref43","doi-asserted-by":"publisher","first-page":"16","DOI":"10.21037\/jlpm.2020.01.01","article-title":"Impact of trimethylamine N-oxide (TMAO) metaorganismal pathway on cardiovascular disease","volume":"5","author":"Zhao","year":"2020","journal-title":"J. Lab Precis Med."}],"container-title":["Frontiers in Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2024.1340262\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,3,5]],"date-time":"2024-03-05T05:08:25Z","timestamp":1709615305000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2024.1340262\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,3,5]]},"references-count":43,"alternative-id":["10.3389\/fmicb.2024.1340262"],"URL":"https:\/\/doi.org\/10.3389\/fmicb.2024.1340262","relation":{},"ISSN":["1664-302X"],"issn-type":[{"value":"1664-302X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,3,5]]},"article-number":"1340262"}}