{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T19:38:43Z","timestamp":1784230723205,"version":"3.55.0"},"reference-count":61,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2020,12,15]],"date-time":"2020-12-15T00:00:00Z","timestamp":1607990400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81570964"],"award-info":[{"award-number":["81570964"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:p>Metabolic-associated fatty liver disease (MAFLD), also known as the hepatic manifestation of metabolic disorders, has become one of the most common chronic liver diseases worldwide. The associations between some oral resident microbes and MAFLD have been described. However, changes to the oral microbial community in patients with MAFLD remain unknown. In this study, variations to the supragingival microbiota of MAFLD patients were identified. The microbial genetic profile of supragingival plaque samples from 24 MAFLD patients and 22 healthy participants were analyzed by 16S rDNA sequencing and bioinformatics analysis. Clinical variables, including indicators of insulin resistance, obesity, blood lipids, and hepatocellular damage, were evaluated with laboratory tests and physical examinations. The results showed that the diversity of the supragingival microbiota in MAFLD patients was signi\ufb01cantly higher than that in healthy individuals. Weighted UniFrac principal coordinates analysis and partial least squares discriminant analysis showed that the samples from the MAFLD and control groups formed separate clusters (Adonis, <jats:italic>P<\/jats:italic> = 0.0120). There were 27 taxa with differential distributions (linear discriminant analysis, LDA&amp;gt;2.0) between two groups, among which <jats:italic>Actinomyces<\/jats:italic> spp. and <jats:italic>Prevotella 2<\/jats:italic> spp. were over-represented in the MAFLD group with highest LDA score, while <jats:italic>Neisseria<\/jats:italic> spp. and <jats:italic>Bergeyella<\/jats:italic> spp. were more abundant in the control group. Co-occurrence networks of the top 50 abundant genera in the two groups suggested that the inter-genera relationships were also altered in the supragingival plaque of MAFLD patients. In addition, in genus level, as risk factors for the development of MAFLD, insulin resistance was positively correlated with the abundances of <jats:italic>Granulicatella<\/jats:italic>, <jats:italic>Veillonella<\/jats:italic>, <jats:italic>Streptococcus<\/jats:italic>, and <jats:italic>Scardovia<\/jats:italic>, while obesity was positively correlated to the abundances of <jats:italic>Streptococcus<\/jats:italic>, <jats:italic>Oslenella<\/jats:italic>, <jats:italic>Scardovia<\/jats:italic>, and <jats:italic>Selenomonas<\/jats:italic>. Metagenomic predictions based on Phylogenetic Investigation of Communities by Reconstruction of Unobserved States revealed that pathways related to sugar (mainly free sugar) metabolism were enriched in the supragingival plaque of the MAFLD group. In conclusion, as compared to healthy individuals, component and interactional dysbioses were observed in the supragingival microbiota of the MAFLD group.<\/jats:p>","DOI":"10.3389\/fcimb.2020.581888","type":"journal-article","created":{"date-parts":[[2021,1,10]],"date-time":"2021-01-10T19:56:44Z","timestamp":1610308604000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":20,"title":["Shifts in the Bacterial Community of Supragingival Plaque Associated With Metabolic-Associated Fatty Liver Disease"],"prefix":"10.3389","volume":"10","author":[{"given":"Fen","family":"Zhao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Dong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ke-Yong","family":"Yuan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ning-Jian","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang-Zhen","family":"Xia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Di","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhi-Min","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying-Li","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zheng-Wei","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2020,12,15]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.94416","article-title":"Microbiota, cirrhosis, and the emergingoral-gut-liver axis","volume":"2","author":"Acharya","year":"2017","journal-title":"JCI Insight"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1038\/srep04828","article-title":"Oral pathobiont induces systemic inflammationand metabolic changes associated with alteration of gut microbiota","volume":"4","author":"Arimatsu","year":"2014","journal-title":"Sci. Rep."},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.3402\/jom.v6.23408","article-title":"Bacteria and bacterial DNA in atheroscleroticplaque and aneurysmal wall biopsies from patients with and without periodontitis","volume":"6","author":"Armingohar","year":"2014","journal-title":"J. Oral. Microbiol."},{"key":"B4","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1902\/annals.1999.4.1.1","article-title":"Development of a classification system for periodontal diseases and conditions","volume":"4","author":"Armitage","year":"1999","journal-title":"Ann. Periodontol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1590\/1807-3107BOR-2015.vol29.0071","article-title":"Supragingival biofilm control and systemicinflammation in patients with type 2 diabetes mellitus","volume":"29","author":"Artese","year":"2015","journal-title":"Braz. Oral. Res."},{"key":"B6","doi-asserted-by":"publisher","first-page":"104","DOI":"10.1111\/jcpe.12190","article-title":"Differences in bacterial saliva profile between periodontitis patients and a control cohort","volume":"41","author":"Belstr\u00f8m","year":"2014","journal-title":"J. Clin. Periodontol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1007\/s00018-018-2947-0","article-title":"Molecular pathways of nonalcoholic fatty liver disease development and progression","volume":"76","author":"Bessone","year":"2019","journal-title":"Cell Mol. Life Sci."},{"key":"B8","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1016\/j.bj.2018.12.001","article-title":"Association between periodontal pathogens and systemic disease","volume":"42","author":"Bui","year":"2019","journal-title":"BioMed. J."},{"key":"B9","doi-asserted-by":"publisher","first-page":"1038","DOI":"10.1016\/j.metabol.2015.12.012","article-title":"The multiple-hit pathogenesis of non-alcoholic fatty liver disease (NAFLD)","volume":"65","author":"Buzzetti","year":"2016","journal-title":"Metabolism"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2015.00119","article-title":"Subgingival microbiota in health compared toperiodontitis and the influence of smoking","volume":"6","author":"Camelo-Castillo","year":"2015","journal-title":"Front. Microbiol."},{"key":"B11","doi-asserted-by":"publisher","first-page":"261","DOI":"10.1038\/s41574-019-0156-z","article-title":"Gut microbial metabolites in obesity, NAFLD and T2DM","volume":"15","author":"Canfora","year":"2019","journal-title":"Nat. Rev. Endocrinol."},{"key":"B12","doi-asserted-by":"publisher","first-page":"774","DOI":"10.1159\/000490029","article-title":"Comparative Analyses of Subgingival Microbiome in Chronic Periodontitis Patients with and Without IgA Nephropathy by High Throughput 16S rRNA Sequencing","volume":"47","author":"Cao","year":"2018","journal-title":"Cell Physiol. Biochem."},{"key":"B13","doi-asserted-by":"publisher","first-page":"328","DOI":"10.1002\/hep.29367","article-title":"The diagnosis and management of nonalcoholic fatty liver disease: Practice guidance from the American Association for the Study of Liver Diseases","volume":"67","author":"Chalasani","year":"2018","journal-title":"Hepatology"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1177\/1533033819867354","article-title":"Role of Oral Microbiome Signatures in Diagnosisand Prognosis of Oral Cancer","volume":"18","author":"Chattopadhyay","year":"2019","journal-title":"Technol. Cancer Res. Treat"},{"key":"B15","doi-asserted-by":"publisher","first-page":"571","DOI":"10.21037\/atm.2019.09.41","article-title":"Variations in gut microbial profiles in ankylosing spondylitis: disease phenotype-related dysbiosis","volume":"7","author":"Chen","year":"2019","journal-title":"Ann. Transl. Med."},{"key":"B16","doi-asserted-by":"publisher","first-page":"564","DOI":"10.1007\/s12020-020-02269-6","article-title":"The oral\u00a0microbiome profile and biomarker inChinese type 2 diabetes mellitus patients","volume":"68","author":"Chen","year":"2020","journal-title":"Endocrine"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2018.01603","article-title":"Microbial Similarity and Preference forSpecific Sites in Healthy Oral Cavity and Esophagus","volume":"9","author":"Dong","year":"2018","journal-title":"Front. Microbiol."},{"key":"B18","doi-asserted-by":"publisher","first-page":"202","DOI":"10.1016\/j.jhep.2020.03.039","article-title":"A new definition for metabolic dysfunction-associated fatty liver disease: An international expert consensus statement","volume":"73","author":"Eslam","year":"2020","journal-title":"J. Hepatol."},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.01631-18","article-title":"Supragingival Plaque Microbiome Ecology andFunctional Potential in the Context of Health and Disease","volume":"9","author":"Espinoza","year":"2018","journal-title":"mBio"},{"key":"B20","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1111\/liv.12977","article-title":"Triglycerides to high-density lipoprotein cholesterol ratio as a surrogate for nonalcoholic fatty liver disease: a cross-sectional study","volume":"18","author":"Fan","year":"2019","journal-title":"Lipids Health Dis."},{"key":"B21","doi-asserted-by":"publisher","first-page":"713","DOI":"10.1111\/liv.12977","article-title":"Triglycerides to high-density lipoproteincholesterol ratio is an independent predictor of incident fatty liver; a population-based cohort study","volume":"36","author":"Fukuda","year":"2016","journal-title":"Liver Int."},{"key":"B22","doi-asserted-by":"publisher","first-page":"148","DOI":"10.1177\/0022034518805739","article-title":"The Oral Microbiota Is Modified by Systemic Diseases","volume":"98","author":"Graves","year":"2019","journal-title":"J. Dent. Res."},{"key":"B23","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1111\/j.1399-302X.2007.00341.x","article-title":"The microbiological profiles of saliva, supragingival and subgingival plaque and dental caries in adults with and without type 2 diabetes mellitus","volume":"22","author":"Hintao","year":"2007","journal-title":"Oral. Microbiol. Immunol."},{"key":"B24","doi-asserted-by":"publisher","first-page":"280","DOI":"10.1007\/s10266-019-00452-4","article-title":"Japanese subgingival microbiota in health vs disease and their roles in predicted functions associated with periodontitis","volume":"108","author":"Ikeda","year":"2020","journal-title":"Odontology"},{"key":"B25","doi-asserted-by":"publisher","first-page":"80","DOI":"10.25100\/cm.v44i2.1123","article-title":"Association between periodontal disease and plasma levels of cholesterol and triglycerides","volume":"44","author":"Jaramillo","year":"2013","journal-title":"Colomb. Med. (Cali)"},{"key":"B26","doi-asserted-by":"publisher","first-page":"956","DOI":"10.1161\/circresaha.116.309219","article-title":"Gut Microbiome Associates With Lifetime Cardiovascular Disease Risk Profile Among Bogalusa Heart Study Participants","volume":"119","author":"Kelly","year":"2016","journal-title":"Circ. Res."},{"key":"B27","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1016\/j.job.2017.05.002","article-title":"Scardovia wiggsiae and its potential role as a caries pathogen","volume":"59","author":"Kressirer","year":"2017","journal-title":"J. Oral. Biosci."},{"key":"B28","doi-asserted-by":"publisher","first-page":"1489","DOI":"10.1902\/jop.2014.140185","article-title":"Association between metabolic syndrome and periodontal disease measures in postmenopausal women: the Buffalo OsteoPerio study","volume":"85","author":"LaMonte","year":"2014","journal-title":"J. Periodontol."},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1038\/s41368-018-0043-9","article-title":"Oral bacteria colonize and compete with gutmicrobiota in gnotobiotic mice","volume":"11","author":"Li","year":"2019","journal-title":"Int. J. Oral. Sci."},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1016\/j.archoralbio.2020.104708","article-title":"Dysbiosis of oral microbiota is associated withsystemic lupus erythematosus","volume":"113","author":"Li","year":"2020","journal-title":"Arch. Oral. Biol."},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2018.00024","article-title":"Ecological Shifts of Supragingival Microbiotain Association with Pregnancy","volume":"8","author":"Lin","year":"2018","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"B32","doi-asserted-by":"publisher","first-page":"49","DOI":"10.17796\/jcpd.36.1.e25411r576362262","article-title":"Association between caries, obesity and insulin resistance in Mexican adolescents","volume":"36","author":"Loyola-Rodriguez","year":"2011","journal-title":"J. Clin. Pediatr. Dent."},{"key":"B33","doi-asserted-by":"publisher","first-page":"1003","DOI":"10.1111\/jcpe.12634","article-title":"Does obesity influence the subgingival microbiota composition in periodontal health and disease","volume":"43","author":"Maciel","year":"2016","journal-title":"J. Clin. Periodontol."},{"key":"B34","doi-asserted-by":"publisher","first-page":"412","DOI":"10.1007\/bf00280883","article-title":"Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man","volume":"28","author":"Matthews","year":"1985","journal-title":"Diabetologia"},{"key":"B35","doi-asserted-by":"publisher","first-page":"2","DOI":"10.21767\/2572-5394.100068","article-title":"Associations of the Oral Microbiota withObesity and Menarche in Inner City Girls","volume":"4","author":"Mervish","year":"2019","journal-title":"J. Child Obes."},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1128\/aem.00462-17","article-title":"Signature of Microbial Dysbiosis inPeriodontitis","volume":"83","author":"Meuric","year":"2017","journal-title":"Appl. Environ. Microbiol."},{"key":"B37","doi-asserted-by":"publisher","first-page":"936","DOI":"10.1111\/zph.12644","article-title":"Bergeyella zoohelcum isolated from oral cavities of therapy dogs","volume":"66","author":"Muramatsu","year":"2019","journal-title":"Zoonoses Public Health"},{"key":"B38","doi-asserted-by":"publisher","first-page":"737","DOI":"10.1016\/j.numecd.2014.01.010","article-title":"Association of serum triglyceride-to-HDL cholesterol ratio with carotid artery intima-media thickness, insulin resistance and nonalcoholic fatty liver disease in children and adolescents","volume":"24","author":"Pacifico","year":"2014","journal-title":"Nutr. Metab. Cardiovasc. Dis."},{"key":"B39","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1111\/jcpe.12811","article-title":"Do different probing depths exhibit striking differences in microbial profiles","volume":"45","author":"Perez-Chaparro","year":"2018","journal-title":"J. Clin. Periodontol."},{"key":"B40","doi-asserted-by":"publisher","first-page":"259","DOI":"10.1007\/s00203-018-1614-z","article-title":"High-resolution novel method for tracking bacteria in a multi-species biofilm","volume":"201","author":"Polak","year":"2019","journal-title":"Arch. Microbiol."},{"key":"B41","doi-asserted-by":"publisher","first-page":"376","DOI":"10.1038\/s41559-020-1099-4","article-title":"Strength of species interactions determines biodiversity and stability in microbial communities","volume":"4","author":"Ratzke","year":"2020","journal-title":"Nat. Ecol. Evol."},{"key":"B42","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1111\/j.1472-765X.2005.01723.x","article-title":"Species-directed 16S rRNA gene nested PCR detection of Olsenella species in association with endodontic diseases","volume":"41","author":"Rocas","year":"2005","journal-title":"Lett. Appl. Microbiol."},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2018.02470","article-title":"Endotoxemia by Porphyromonas gingivalisInjection Aggravates Non-alcoholic Fatty Liver Disease, Disrupts Glucose\/Lipid Metabolism, andAlters Gut Microbiota in Mice","volume":"9","author":"Sasaki","year":"2018","journal-title":"Front. Microbiol."},{"key":"B44","doi-asserted-by":"publisher","first-page":"36","DOI":"10.2334\/josnusd.19-0021","article-title":"Contribution of different adherent properties of Granulicatella adiacens and Abiotrophia defectiva to their associations with oral colonization and the risk of infective endocarditis","volume":"62","author":"Sasaki","year":"2020","journal-title":"J. Oral. Sci."},{"key":"B45","doi-asserted-by":"publisher","first-page":"R42","DOI":"10.1186\/gb-2012-13-6-r42","article-title":"Composition of the adult digestive tract bacterial microbiome based on seven mouth surfaces, tonsils, throat and stool samples","volume":"13","author":"Segata","year":"2012","journal-title":"Genome Biol."},{"key":"B46","doi-asserted-by":"publisher","first-page":"1175","DOI":"10.1001\/jama.2020.2298","article-title":"Nonalcoholic Steatohepatitis: A Review","volume":"323","author":"Sheka","year":"2020","journal-title":"JAMA"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2017.00516","article-title":"Oral Microbiota: Microbial Biomarkers of Metabolic Syndrome Independent of Host Genetic Factors","volume":"7","author":"Si","year":"2017","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2019.00369","article-title":"Characteristics of Gut Microbiota in PatientsWith Rheumatoid Arthritis in Shanghai, China","volume":"9","author":"Sun","year":"2019","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1038\/srep22164","article-title":"Bacterial diversity in saliva and oralhealth-related conditions: the Hisayama Study","volume":"6","author":"Takeshita","year":"2016","journal-title":"Sci. Rep."},{"key":"B50","doi-asserted-by":"publisher","first-page":"e0204724","DOI":"10.1371\/journal.pone.0204724","article-title":"Obesity alters composition and diversity of the oral microbiota in patients with type 2 diabetes mellitus independently of glycemic control","volume":"13","author":"Tam","year":"2018","journal-title":"PloS One"},{"key":"B51","doi-asserted-by":"publisher","first-page":"380","DOI":"10.5582\/ddt.2015.01207","article-title":"Optimal cut-off values for the homeostasis model assessment of insulin resistance (HOMA-IR) and pre-diabetes screening: Developments in research and prospects for the future","volume":"9","author":"Tang","year":"2015","journal-title":"Drug Discov. Ther."},{"key":"B52","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1016\/j.job.2014.08.001","article-title":"Anaerobic culture to detect periodontal and caries pathogens","volume":"57","author":"Tanner","year":"2015","journal-title":"J. Oral. Biosci."},{"key":"B53","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1146\/annurev-pathol-121808-102132","article-title":"Nonalcoholic fatty liver disease: pathology and pathogenesis","volume":"5","author":"Tiniakos","year":"2010","journal-title":"Annu. Rev. Pathol."},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2019.00475","article-title":"Oral Microbiota Perturbations Are Linked toHigh Risk for Rheumatoid Arthritis","volume":"9","author":"Tong","year":"2019","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"B55","doi-asserted-by":"publisher","first-page":"242","DOI":"10.1038\/nature11552","article-title":"Functional interactions between the gut microbiota and host metabolism","volume":"489","author":"Tremaroli","year":"2012","journal-title":"Nature"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2016.00564","article-title":"Individuality, Stability, and Variability of thePlaque Microbiome","volume":"7","author":"Utter","year":"2016","journal-title":"Front. Microbiol."},{"key":"B57","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1016\/j.micpath.2015.09.009","article-title":"Periodontal-disease-associated biofilm: A reservoir for pathogens of medical importance","volume":"94","author":"Vieira Colombo","year":"2016","journal-title":"Microb. Pathog."},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1016\/j.abb.2020.108278","article-title":"Identification of hyperglycemia-associatedmicrobiota alterations in saliva and gingival sulcus","volume":"682","author":"Wei","year":"2020","journal-title":"Arch. Biochem. Biophys."},{"key":"B59","doi-asserted-by":"publisher","first-page":"201","DOI":"10.2334\/josnusd.16-0856","article-title":"The oral microbiome and human health","volume":"59","author":"Yamashita","year":"2017","journal-title":"J. Oral. Sci."},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1186\/1471-230x-12-16","article-title":"Involvement of a periodontal pathogen, Porphyromonas gingivalis on the pathogenesis of non-alcoholic fatty liver disease","volume":"12","author":"Yoneda","year":"2012","journal-title":"BMC Gastroenterol."},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.21203\/rs.3.rs-45886\/v1","article-title":"Shifts in the bacterial community of supragingival plaque related to metabolic associated fatty liver disease","author":"Zhao","year":"2020","journal-title":"Preprint"}],"container-title":["Frontiers in Cellular and Infection Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2020.581888\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,1,10]],"date-time":"2021-01-10T19:56:46Z","timestamp":1610308606000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2020.581888\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,12,15]]},"references-count":61,"alternative-id":["10.3389\/fcimb.2020.581888"],"URL":"https:\/\/doi.org\/10.3389\/fcimb.2020.581888","relation":{},"ISSN":["2235-2988"],"issn-type":[{"value":"2235-2988","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,12,15]]},"article-number":"581888"}}