{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T13:58:34Z","timestamp":1791899914547,"version":"4.3.4"},"reference-count":62,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,9,17]],"date-time":"2024-09-17T00:00:00Z","timestamp":1726531200000},"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. Cell. Infect. Microbiol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Colorectal cancer (CRC) poses a global health threat, with the oral microbiome increasingly implicated in its pathogenesis. This study leverages Mendelian Randomization (MR) to explore causal links between oral microbiota and CRC using data from the China National GeneBank and Biobank Japan. By integrating multi-omics approaches, we aim to uncover mechanisms by which the microbiome influences cellular metabolism and cancer development.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We analyzed microbiome profiles from 2017 tongue and 1915 saliva samples, and GWAS data for 6692 CRC cases and 27178 controls. Significant bacterial taxa were identified via MR analysis. Single-cell RNA sequencing and enrichment analyses elucidated underlying pathways, and drug predictions identified potential therapeutics.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>MR identified 19 bacterial taxa significantly associated with CRC. Protective effects were observed in taxa like RUG343 and Streptococcus_umgs_2425, while HOT-345_umgs_976 and W5053_sp000467935_mgs_712 increased CRC risk. Single-cell RNA sequencing revealed key pathways, including JAK-STAT signaling and tyrosine metabolism. Drug prediction highlighted potential therapeutics like Menadione Sodium Bisulfite and Raloxifene.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This study establishes the critical role of the oral microbiome in colorectal cancer development, identifying specific microbial taxa linked to CRC risk. Single-cell RNA sequencing and drug prediction analyses further elucidate key pathways and potential therapeutics, providing novel insights and personalized treatment strategies for CRC.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fcimb.2024.1452392","type":"journal-article","created":{"date-parts":[[2024,9,18]],"date-time":"2024-09-18T14:53:41Z","timestamp":1726671221000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":24,"title":["Revealing the association between East Asian oral microbiome and colorectal cancer through Mendelian randomization and multi-omics analysis"],"prefix":"10.3389","volume":"14","author":[{"given":"Yuheng","family":"Gu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lai","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Shui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Honghao","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuancheng","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shengke","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenglu","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinbang","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haiqing","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingyi","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiping","family":"Fu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huiyan","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guanhu","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ke","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Chi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shangke","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,9,17]]},"reference":[{"key":"B1","first-page":"5257","article-title":"Modulation of cytotoxicity of menadione sodium bisulfite versus leukemia L1210 by the acid-soluble thiol pool","volume":"45","author":"Akman","year":"1985","journal-title":"Cancer Res."},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1101\/2021.02.24.432654","article-title":"Fiber-associated Lachnospiraceae reduce colon tumorigenesis by modulation of the tumor-immune microenvironment","author":"Almeida","year":"2021"},{"key":"B3","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1186\/s13099-015-0074-0","article-title":"Streptococcus bovis infectious endocarditis and occult gastrointestinal neoplasia: experience with 25 consecutive patients treated surgically","volume":"7","author":"Alozie","year":"2015","journal-title":"Gut Pathog."},{"key":"B4","doi-asserted-by":"publisher","first-page":"351","DOI":"10.3390\/cancers10100351","article-title":"Combined effect of bortezomib and menadione sodium bisulfite on proteasomes of tumor cells: the dramatic decrease of bortezomib toxicity in a preclinical trial","volume":"10","author":"Astakhova","year":"2018","journal-title":"Cancers"},{"key":"B5","doi-asserted-by":"crossref","first-page":"2792","DOI":"10.1182\/blood-2021-153117","article-title":"High bacterial abundances of dorea and\npediococcus in the gut microbiome linked to expansion, immune checkpoint expression and efficacy of\nCD19-directed CAR T-cells in patients with r\/r DLBCL","volume":"138","author":"Blumenberg","year":"2021","journal-title":"Blood"},{"key":"B6","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":"B7","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":"B8","doi-asserted-by":"publisher","DOI":"10.1002\/jrsm.1346","article-title":"Meta-analysis and Mendelian randomization: A\nreview","volume":"10","author":"Bowden","year":"2019","journal-title":"Res. synthesis Methods"},{"key":"B9","doi-asserted-by":"publisher","first-page":"251","DOI":"10.1093\/aje\/kwu283","article-title":"Multivariable Mendelian randomization: the use of pleiotropic genetic variants to estimate causal effects","volume":"181","author":"Burgess","year":"2015","journal-title":"Am. J. Epidemiol."},{"key":"B10","doi-asserted-by":"publisher","first-page":"S67","DOI":"10.1007\/BF01640857","article-title":"Campylobacter enteritis","author":"Butzler","year":"1982","journal-title":"Infection"},{"key":"B11","doi-asserted-by":"publisher","first-page":"4133","DOI":"10.3390\/ijms20174133","article-title":"A cell\u2019s fate: an overview of the molecular biology and genetics of apoptosis","volume":"20","author":"Cavalcante","year":"2019","journal-title":"Int. J. Mol. Sci."},{"key":"B12","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1186\/s12974-021-02175-2","article-title":"Tryptophan-kynurenine metabolism: a link between the gut and brain for depression in inflammatory bowel disease","volume":"18","author":"Chen","year":"2021","journal-title":"J. Neuroinflamm."},{"key":"B13","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1186\/s40168-021-01208-5","article-title":"Altered gut metabolites and microbiota interactions are implicated in colorectal carcinogenesis and can be non-invasive diagnostic biomarkers","volume":"10","author":"Coker","year":"2022","journal-title":"Microbiome"},{"key":"B14","doi-asserted-by":"publisher","first-page":"504","DOI":"10.1016\/S1470-2045(10)70186-8","article-title":"Microbial and viral pathogens in colorectal cancer","volume":"12","author":"Collins","year":"2011","journal-title":"Lancet Oncol."},{"key":"B15","doi-asserted-by":"publisher","first-page":"3385","DOI":"10.3390\/cancers14143385","article-title":"The tissue-associated microbiota in colorectal cancer: A systematic review","volume":"14","author":"Costa","year":"2022","journal-title":"Cancers"},{"key":"B16","doi-asserted-by":"publisher","first-page":"R89","DOI":"10.1093\/hmg\/ddu328","article-title":"Mendelian randomization: genetic anchors for causal inference in epidemiological studies","volume":"23","author":"Davey Smith","year":"2014","journal-title":"Hum. Mol. Genet."},{"key":"B17","doi-asserted-by":"publisher","first-page":"1756284818783606","DOI":"10.1177\/1756284818783606","article-title":"The controversial role of Enterococcus faecalis in colorectal cancer","volume":"11","author":"de Almeida","year":"2018","journal-title":"Ther. Adv. Gastroenterol."},{"key":"B18","doi-asserted-by":"publisher","first-page":"1925","DOI":"10.1001\/jama.2017.17219","article-title":"Mendelian randomization","volume":"318","author":"Emdin","year":"2017","journal-title":"JAMA"},{"key":"B19","doi-asserted-by":"publisher","first-page":"835","DOI":"10.1111\/jop.13014","article-title":"The role of Candida albicans candidalysin ECE1 gene in oral carcinogenesis","volume":"49","author":"Engku Nasrullah Satiman","year":"2020","journal-title":"J. Oral. Pathol. Medicine: Off. Publ. Int. Assoc. Oral. Pathologists Am. Acad. Oral. Pathol."},{"key":"B20","doi-asserted-by":"publisher","first-page":"D1144","DOI":"10.1093\/nar\/gkaa1084","article-title":"Integration of the Drug-Gene Interaction Database (DGIdb 4.0) with open crowdsource efforts","volume":"49","author":"Freshour","year":"2021","journal-title":"Nucleic Acids Res."},{"key":"B21","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":"B22","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1136\/gutjnl-2018-317200","article-title":"Campylobacter jejuni promotes colorectal tumorigenesis through the action of cytolethal distending toxin","volume":"68","author":"He","year":"2019","journal-title":"Gut"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1007081","article-title":"Orienting the causal relationship between imprecisely measured traits using GWAS summary data","volume":"13","author":"Hemani","year":"2017","journal-title":"PloS Genet."},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.3389\/fbioe.2023.1110765","article-title":"JAK\/STAT pathway: Extracellular signals, diseases, immunity, and therapeutic regimens","volume":"11","author":"Hu","year":"2023","journal-title":"Front. Bioengineering Biotechnol."},{"key":"B25","doi-asserted-by":"publisher","first-page":"1789","DOI":"10.1101\/gr.267997.120","article-title":"Ultrafast and scalable variant annotation and prioritization with big functional genomics data","volume":"30","author":"Huang","year":"2020","journal-title":"Genome Res."},{"key":"B26","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1186\/s40168-022-01388-8","article-title":"Enterotypical Prevotella and three novel bacterial biomarkers in preoperative stool predict the clinical outcome of colorectal cancer","volume":"10","author":"Huh","year":"2022","journal-title":"Microbiome"},{"key":"B27","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1158\/1940-6207.CAPR-08-0140","article-title":"Estrogen receptor-beta as a potential target for colon cancer prevention: chemoprevention of azoxymethane-induced colon carcinogenesis by raloxifene in F344 rats","volume":"2","author":"Janakiram","year":"2009","journal-title":"Cancer Prev. Res."},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1400431","article-title":"Mitophagy and clear cell renal cell carcinoma: insights from single-cell and spatial transcriptomics analysis","volume":"15","author":"Jiang","year":"2024","journal-title":"Front. Immunol."},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2020.596570","article-title":"Review on stress tolerance in campylobacter jejuni","volume":"10","author":"Kim","year":"2020","journal-title":"Front. Cell. Infection Microbiol."},{"key":"B30","doi-asserted-by":"publisher","first-page":"383","DOI":"10.1053\/j.gastro.2018.04.028","article-title":"Association between bacteremia from specific microbes and subsequent diagnosis of colorectal cancer","volume":"155","author":"Kwong","year":"2018","journal-title":"Gastroenterology"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1111\/cns.14812","article-title":"Causal relationship and shared genes between air pollutants and amyotrophic lateral sclerosis: A large-scale genetic analysis","volume":"30","author":"Li","year":"2024","journal-title":"CNS Neurosci. Ther."},{"key":"B32","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1038\/s41421-021-00356-0","article-title":"Metagenome-genome-wide association studies reveal human genetic impact on the oral microbiome","volume":"7","author":"Liu","year":"2021","journal-title":"Cell Discovery"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2023.1178051","article-title":"Causal relationship between ischemic stroke and its subtypes and frozen shoulder: a two-sample Mendelian randomization analysis","volume":"14","author":"Lv","year":"2023","journal-title":"Front. Neurol."},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2024.1309111","article-title":"Association between the gut microbiota, inflammatory factors, and colorectal cancer: evidence from Mendelian randomization analysis","volume":"15","author":"Ma","year":"2024","journal-title":"Front. Microbiol."},{"key":"B35","doi-asserted-by":"publisher","first-page":"214","DOI":"10.3390\/metabo14040214","article-title":"Unveiling the nexus: cellular metabolomics unravels the impact of estrogen on nicotinamide metabolism in mitigating rheumatoid arthritis pathogenesis","volume":"14","author":"Malik","year":"2024","journal-title":"Metabolites"},{"key":"B36","doi-asserted-by":"publisher","first-page":"2076","DOI":"10.1158\/1538-7445.AM2012-2076","article-title":"Abstract 2076: Oxidative stress induced by sodium ascorbate:menadione sodium-bisulfate combination results in lysosomal and mitochondrial changes that lead to prostate cancer cell death","volume":"72","author":"McGuire","year":"2012","journal-title":"Cancer Res."},{"key":"B37","doi-asserted-by":"publisher","first-page":"1296","DOI":"10.1136\/gutjnl-2022-327337","article-title":"Rewiring the altered tryptophan metabolism as a novel therapeutic strategy in inflammatory bowel diseases","volume":"72","author":"Michaudel","year":"2023","journal-title":"Gut"},{"key":"B38","doi-asserted-by":"publisher","first-page":"476068","DOI":"10.1155\/2014\/476068","article-title":"Porphyromonas gingivalis: major periodontopathic pathogen overview","volume":"2014","author":"Mysak","year":"2014","journal-title":"J. Immunol. Res."},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.573158","article-title":"Significant and conflicting correlation of IL-9 with prevotella and bacteroides in human colorectal cancer","volume":"11","author":"Niccolai","year":"2020","journal-title":"Front. Immunol."},{"key":"B40","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1159\/000452708","article-title":"Periodontal pathogens in the etiology of pancreatic cancer","volume":"3","author":"\u00d6\u011frendik","year":"2017","journal-title":"Gastrointestinal Tumors"},{"key":"B41","doi-asserted-by":"publisher","first-page":"4053","DOI":"10.3748\/wjg.v28.i30.4053","article-title":"Gut microbiota, inflammatory bowel disease and colorectal cancer","volume":"28","author":"Quaglio","year":"2022","journal-title":"World J. Gastroenterol."},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2022.821344","article-title":"JAK\/STAT signaling: molecular targets, therapeutic opportunities, and limitations of targeted inhibitions in solid Malignancies","volume":"13","author":"Rah","year":"2022","journal-title":"Front. Pharmacol."},{"key":"B43","doi-asserted-by":"publisher","first-page":"192","DOI":"10.3390\/cancers15010192","article-title":"Oral microbiota as novel biomarkers for colorectal cancer screening","volume":"15","author":"Rezasoltani","year":"2022","journal-title":"Cancers"},{"key":"B44","doi-asserted-by":"publisher","first-page":"2973","DOI":"10.3390\/ijms22062973","article-title":"Tryptophan metabolism and gut-brain homeostasis","volume":"22","author":"Roth","year":"2021","journal-title":"Int. J. Mol. Sci."},{"key":"B45","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1186\/s12964-017-0177-y","article-title":"The role of JAK-STAT signaling pathway and its regulators in the fate of T helper cells","volume":"15","author":"Seif","year":"2017","journal-title":"Cell communication signaling: CCS"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1002\/imt2.36","article-title":"Sangerbox: A comprehensive, interaction-friendly clinical bioinformatics analysis platform","volume":"1","author":"Shen","year":"2022","journal-title":"iMeta"},{"key":"B47","doi-asserted-by":"publisher","first-page":"121476","DOI":"10.1016\/j.envpol.2023.121476","article-title":"Long-term DEHP\/MEHP exposure promotes colorectal cancer stemness associated with glycosylation alterations","volume":"327","author":"Shih","year":"2023","journal-title":"Environ. pollut."},{"key":"B48","doi-asserted-by":"publisher","first-page":"2897","DOI":"10.3390\/foods12152897","article-title":"Enhanced production of \u03b2-nicotinamide mononucleotide with exogenous nicotinamide addition in saccharomyces boulardii-YS01","volume":"12","author":"Song","year":"2023","journal-title":"Foods"},{"key":"B49","doi-asserted-by":"publisher","first-page":"209","DOI":"10.3322\/caac.21660","article-title":"Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA: Cancer J. Clin."},{"key":"B50","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":"B51","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1038\/s41522-021-00248-x","article-title":"Western and non-western gut microbiomes reveal new roles of Prevotella in carbohydrate metabolism and mouth-gut axis","volume":"7","author":"Vishnu Prasoodanan","year":"2021","journal-title":"NPJ biofilms microbiomes"},{"key":"B52","doi-asserted-by":"publisher","first-page":"234","DOI":"10.3390\/biomedicines10020234","article-title":"Decreased SLC27A5 suppresses lipid synthesis and tyrosine metabolism to activate the cell cycle in hepatocellular carcinoma","volume":"10","author":"Wang","year":"2022","journal-title":"Biomedicines"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.33596","article-title":"Alterations in the oral and gut microbiome of colorectal cancer patients and association with host clinical factors","author":"Wang","year":"2021","journal-title":"Int. J. Cancer"},{"key":"B54","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1186\/2049-2618-1-16","article-title":"Co-occurrence of anaerobic bacteria in colorectal carcinomas","volume":"1","author":"Warren","year":"2013","journal-title":"Microbiome"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.86416","article-title":"The next step in Mendelian randomization","volume":"12","author":"Weith","year":"2023","journal-title":"eLife"},{"key":"B56","doi-asserted-by":"publisher","first-page":"100141","DOI":"10.1016\/j.xinn.2021.100141","article-title":"clusterProfiler 4.0: A universal enrichment tool for interpreting omics data","volume":"2","author":"Wu","year":"2021","journal-title":"Innovation (Cambridge (Mass.))"},{"key":"B57","doi-asserted-by":"publisher","first-page":"101174","DOI":"10.1016\/j.tranon.2021.101174","article-title":"Global colorectal cancer burden in 2020 and projections to 2040","volume":"14","author":"Xi","year":"2021","journal-title":"Trans. Oncol."},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1126\/science.abf3041","article-title":"Single-cell eQTL mapping identifies cell type-specific genetic control of autoimmune disease","volume":"376","author":"Yazar","year":"2022","journal-title":"Science"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2024.1309917","article-title":"Identification and validation of NAD+ metabolism-related biomarkers in patients with diabetic peripheral neuropathy","volume":"15","author":"Ye","year":"2024","journal-title":"Front. Endocrinol."},{"key":"B60","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1186\/s13046-021-01971-1","article-title":"Targeting SERT promotes tryptophan metabolism: mechanisms and implications in colon cancer treatment","volume":"40","author":"Ye","year":"2021","journal-title":"J. Exp. Clin. Cancer research: CR"},{"key":"B61","doi-asserted-by":"publisher","first-page":"174","DOI":"10.1186\/s12964-024-01552-7","article-title":"Tryptophan metabolism in digestive system tumors: unraveling the pathways and implications","volume":"22","author":"Yu","year":"2024","journal-title":"Cell communication signaling: CCS"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2014.00085","article-title":"Acquiring and maintaining a normal oral microbiome: current perspective","volume":"4","author":"Zaura","year":"2014","journal-title":"Front. Cell. Infection Microbiol."}],"container-title":["Frontiers in Cellular and Infection Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2024.1452392\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,9,18]],"date-time":"2024-09-18T22:17:15Z","timestamp":1726697835000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2024.1452392\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,9,17]]},"references-count":62,"alternative-id":["10.3389\/fcimb.2024.1452392"],"URL":"https:\/\/doi.org\/10.3389\/fcimb.2024.1452392","relation":{},"ISSN":["2235-2988"],"issn-type":[{"value":"2235-2988","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,9,17]]},"article-number":"1452392"}}