{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T16:40:28Z","timestamp":1791823228303,"version":"4.3.4"},"reference-count":60,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,1,18]],"date-time":"2023-01-18T00:00:00Z","timestamp":1674000000000},"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. Nutr."],"abstract":"<jats:p>In recent years, the global incidence of liver damage has increased. Despite the many known health benefits of red-fleshed apple flavonoids, their potential liver-protective effects have not yet been investigated. In this study, we analyzed the composition of red-fleshed apple flavonoid extract (RAFE) by high-performance liquid chromatography (HPLC). We then induced liver damage in mice with carbon tetrachloride (CCl<jats:sub>4<\/jats:sub>) and performed interventions with RAFE to analyze its effect on liver damage, using bifendate as a positive control. The results showed that catechin was the most abundant flavonoid in \u2018XJ4\u2019 RAFE (49.346 mg\/100 g). In liver-injured mice, the liver coefficients converged to normal levels following RAFE intervention. Moreover, RAFE significantly reduced the enzymatic activity levels of glutamic oxaloacetic transaminase (ALT), glutamic alanine transaminase (AST), and alkaline phosphatase (ALP) in mouse serum. Furthermore, RAFE significantly increased the content or enzyme activity level of total glutathione, total antioxidant capacity, and superoxide dismutase, and significantly decreased the content of malondialdehyde in the liver of mice. In parallel, we performed histopathological observations of mouse livers for each group. The results showed that RAFE restored the pathological changes caused by CCl<jats:sub>4<\/jats:sub> around the central hepatic vein in mice and resulted in tightly bound hepatocytes. The recovery effect of RAFE was dose-dependent in the liver tissue. Regarding intestinal microorganisms, we found that RAFE restored the microbial diversity in liver-injured mice, with a similar microbial composition in the RAFE intervention group and normal group. RAFE reduced the ratio of <jats:italic>Firmicutes<\/jats:italic> to <jats:italic>Bacteroidetes<\/jats:italic>, increased the levels of probiotic bacteria, such as <jats:italic>Lactobacillus acidophilus<\/jats:italic>, and <jats:italic>Clostridium<\/jats:italic>, and reduced the levels of harmful bacteria, such as <jats:italic>Erysipelothrix Rosenbach.<\/jats:italic> Therefore, RAFE ameliorated CCl<jats:sub>4<\/jats:sub>-induced liver damage by modulating the abundance and composition of intestinal microorganisms in mice. In conclusion, RAFE alleviated CCl<jats:sub>4<\/jats:sub>-induced liver damage in mice, with H-RAFE (5 mg kg<jats:sup>\u20131<\/jats:sup>) significantly improving liver damage in mice but M-RAFE (1 mg kg<jats:sup>\u20131<\/jats:sup>) significantly improving the imbalance of intestinal microorganisms in mice. Our research suggests that RAFE could be employed for the adjuvant treatment and prevention of liver damage, and may have important applications in food and medicine.<\/jats:p>","DOI":"10.3389\/fnut.2022.1098954","type":"journal-article","created":{"date-parts":[[2023,1,18]],"date-time":"2023-01-18T11:56:58Z","timestamp":1674043018000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":10,"title":["Red-fleshed apple flavonoid extract alleviates CCl4-induced liver injury in mice"],"prefix":"10.3389","volume":"9","author":[{"given":"Yizhou","family":"Chen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanbo","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shenghui","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jihua","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohong","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yugang","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,1,18]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22147702","article-title":"Mitochondria matter: systemic aspects of nonalcoholic fatty liver disease (NAFLD) and diagnostic assessment of liver function by stable isotope dynamic breath tests.","volume":"22","author":"Di Ciaula","year":"2021","journal-title":"Int J Mol Sci."},{"key":"B2","article-title":"Physiology, liver.","author":"Kalra","year":"2022","journal-title":"StatPearls."},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1038\/s41572-019-0105-0","article-title":"Drug-induced liver injury.","volume":"5","author":"Andrade","year":"2019","journal-title":"Nat Rev Dis Primers."},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2021.688780","article-title":"Gut microbiota and chemical-induced acute liver injury.","volume":"12","author":"Chen","year":"2021","journal-title":"Front Physiol."},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1155\/2018\/6921845","article-title":"A Sargassum fluitans borgesen ethanol extract exhibits a hepatoprotective effect in vivo in acute and chronic liver damage models.","volume":"2018","author":"Quintal-Novelo","year":"2018","journal-title":"BioMed Res Int."},{"key":"B6","doi-asserted-by":"publisher","first-page":"347","DOI":"10.1016\/j.jep.2009.02.023","article-title":"Hepatoprotective effect of Trichosanthes cucumerina var cucumerina L. on carbon tetrachloride induced liver damage in rats.","volume":"123","author":"Kumar","year":"2009","journal-title":"J Ethnopharmacol."},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.4103\/phrev.phrev_52_17","article-title":"A review on some medicinal plants with hepatoprotective effects.","volume":"12","author":"Okaiyeto","year":"2018","journal-title":"Pharmacogn Mag."},{"key":"B8","first-page":"166","article-title":"Development of phytomedicine for liver diseases.","volume":"31","author":"Subramoniam","year":"1999","journal-title":"Indian J Pharmacol."},{"key":"B9","doi-asserted-by":"publisher","first-page":"517","DOI":"10.1586\/17474124.2016.1127756","article-title":"Current and future directions in the treatment and prevention of drug-induced liver injury: a systematic review.","volume":"10","author":"Stine","year":"2016","journal-title":"Expert Rev Gastroenterol Hepatol."},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2021.119544","article-title":"Drug-induced liver injury and prospect of cytokine based therapy; a focus on IL-2 based therapies.","volume":"278","author":"Kumar","year":"2021","journal-title":"Life Sci."},{"key":"B11","doi-asserted-by":"publisher","first-page":"2065","DOI":"10.1002\/hep.23937","article-title":"Drug-induced acute liver failure: results of a U.S. Multicenter, prospective study.","volume":"52","author":"Reuben","year":"2010","journal-title":"Hepatology."},{"key":"B12","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1016\/j.taap.2011.02.004","article-title":"Comparison of imatinib, nilotinib and silymarin in the treatment of carbon tetrachloride-induced hepatic oxidative stress, injury and fibrosis.","volume":"252","author":"Shaker","year":"2011","journal-title":"Toxicol Appl Pharmacol."},{"key":"B13","doi-asserted-by":"publisher","first-page":"468","DOI":"10.1080\/01480545.2018.1504960","article-title":"Protective effects of combined losartan and nilotinib on carbon tetrachloride (CCl)-induced liver fibrosis in rats.","volume":"43","author":"Karimi","year":"2020","journal-title":"Drug Chem Toxicol."},{"key":"B14","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1615\/JEnvironPatholToxicolOncol.2017019824","article-title":"The hepatoprotective effect of clidemia hirta against carbon tetrachloride (CCl4)-induced oxidative stress and hepatic damage in mice.","volume":"36","author":"Amzar","year":"2017","journal-title":"J Environ Pathol Toxicol Oncol."},{"key":"B15","doi-asserted-by":"publisher","first-page":"14787","DOI":"10.3748\/wjg.v20.i40.14787","article-title":"Review of natural products with hepatoprotective effects.","volume":"20","author":"Madrigal-Santill\u00e1n","year":"2014","journal-title":"World J Gastroenterol."},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1186\/s12199-017-0673-0","article-title":"The potential protective effect of Commelina nudiflora L. against carbon tetrachloride (CCl4)-induced hepatotoxicity in rats, mediated by suppression of oxidative stress and inflammation.","volume":"22","author":"Shah","year":"2017","journal-title":"Environ Health Prev Med."},{"key":"B17","doi-asserted-by":"publisher","first-page":"p. 89","DOI":"10.1016\/B978-0-12-803269-5.00004-8","article-title":"Chapter Four - oxidative stress and biomaterials: the inflammatory link.","author":"Adjei","year":"2016","journal-title":"Oxidative Stress and Biomaterials."},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.3390\/molecules27051533","article-title":"Hepatoprotective potential of Malaysian medicinal plants: a review on phytochemicals, oxidative stress, and antioxidant mechanisms.","volume":"27","author":"Venmathi Maran","year":"2022","journal-title":"Molecules."},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1186\/s43066-021-00161-0","article-title":"Medicinal plants with hepatoprotective potentials against carbon tetrachloride-induced toxicity: a review.","volume":"11","author":"Ugwu","year":"2021","journal-title":"Egypt Liver J."},{"key":"B20","doi-asserted-by":"publisher","first-page":"1574","DOI":"10.9734\/BJMMR\/2013\/3762","article-title":"Hepatoprotective and antioxidant effect of hibiscus polyphenol rich extract (HPE) against carbon tetrachloride (CCL4) \u2013induced damage in rats.","volume":"3","author":"Adewale","year":"2010","journal-title":"J Adv Med."},{"key":"B21","doi-asserted-by":"publisher","first-page":"795","DOI":"10.1016\/j.jnutbio.2006.12.016","article-title":"Green tea polyphenol epigallocatechin-3-gallate inhibits oxidative damage and preventive effects on carbon tetrachloride\u2013induced hepatic fibrosis.","volume":"18","author":"Zhen","year":"2007","journal-title":"J Nutr Biochem."},{"key":"B22","doi-asserted-by":"publisher","first-page":"1393","DOI":"10.1211\/jpp\/60.10.0016","article-title":"Protective effects of total flavonoids of Bidens bipinnata L. against carbon tetrachloride-induced liver fibrosis in rats.","volume":"60","author":"Li","year":"2010","journal-title":"J Pharm Pharmacol."},{"key":"B23","doi-asserted-by":"publisher","first-page":"1017","DOI":"10.1211\/jpp.59.7.0015","article-title":"Protective effect of total flavonoids from Bidens bipinnata L. against carbon tetrachloride-induced liver injury in mice.","volume":"59","author":"Zhong","year":"2010","journal-title":"J Pharm Pharmacol."},{"key":"B24","doi-asserted-by":"publisher","first-page":"534","DOI":"10.21273\/HORTSCI.45.4.534","article-title":"Efficient breeding system for red-fleshed apple based on linkage with S3-RNase allele in \u2018pink pearl\u2019.","volume":"45","author":"Sekido","year":"2010","journal-title":"Hortscience."},{"key":"B25","doi-asserted-by":"publisher","first-page":"4861","DOI":"10.1039\/d2fo00130f","article-title":"New red-fleshed apple cultivars: a comprehensive review of processing effects, (poly)phenol bioavailability and biological effects.","volume":"13","author":"Yuste","year":"2022","journal-title":"Food Funct."},{"key":"B26","doi-asserted-by":"publisher","first-page":"277","DOI":"10.16420\/j.issn.0513-353x.2008.02.009","article-title":"Genetic diversity of mineral elements, sugar and acid components in Malus sieversii(Ldb.)roem.","volume":"35","author":"Zhang","year":"2008","journal-title":"Acta Hortic."},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.3390\/molecules25081968","article-title":"Analysis of antioxidant activity and flavonoids metabolites in peel and flesh of red-fleshed apple varieties.","volume":"25","author":"Zhang","year":"2020","journal-title":"Molecules."},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.3389\/fnut.2021.632483","article-title":"Red-fleshed apple anthocyanin extracts attenuate male reproductive system dysfunction caused by busulfan in mice.","volume":"8","author":"Xu","year":"2021","journal-title":"Front Nutr."},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.3389\/fnut.2021.802352","article-title":"Combined analysis of gut microbiota and plasma metabolites reveals the effect of red-fleshed apple anthocyanin extract on dysfunction of mice reproductive system induced by busulfan.","volume":"8","author":"Wang","year":"2022","journal-title":"Front Nutr."},{"key":"B30","doi-asserted-by":"publisher","first-page":"p. 176","DOI":"10.1007\/978-3-030-96641-6_21","article-title":"The study of the quantitative content of flavonoids and biological activity of the herba Thlaspi arvense L.","author":"Pupykina","year":"2022","journal-title":"Intelligent Biotechnologies of Natural and Synthetic Biologically Active Substances."},{"key":"B31","doi-asserted-by":"publisher","first-page":"305","DOI":"10.2174\/1568026622666220117111858","article-title":"Recent developments of flavonoids with various activities.","volume":"22","author":"Sun","year":"2022","journal-title":"Curr Top Med Chem."},{"key":"B32","doi-asserted-by":"publisher","first-page":"321","DOI":"10.1016\/j.foodchem.2018.12.019","article-title":"Flavonoids, phenolic acids, carotenoids and antioxidant activity of fresh eating citrus fruits, using the coupled in vitro digestion and human intestinal HepG2 cells model.","volume":"279","author":"Sun","year":"2019","journal-title":"Food Chem."},{"key":"B33","doi-asserted-by":"publisher","first-page":"421","DOI":"10.1007\/s40415-019-00552-z","article-title":"An analyses of flavonoids present in the inflorescence of sunflower.","volume":"42","author":"Sharma","year":"2019","journal-title":"Braz J Bot."},{"key":"B34","doi-asserted-by":"publisher","first-page":"6347","DOI":"10.1021\/jf0346298","article-title":"Polyphenolic profiles in eight apple cultivars using high-performance liquid chromatography (HPLC).","volume":"51","author":"Rong","year":"2003","journal-title":"J Agric Food Chem."},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1186\/s13065-022-00822-0","article-title":"Analysis of total phenolic contents, flavonoids, antioxidant and antibacterial activities of Croton macrostachyusroot extracts.","volume":"16","author":"Ayele","year":"2022","journal-title":"BMC Chem."},{"key":"B36","doi-asserted-by":"publisher","first-page":"933","DOI":"10.1016\/0891-5849(95)02227-9","article-title":"Structure-antioxidant activity relationships of flavonoids and phenolic acids.","volume":"20","author":"Rice-Evans","year":"1996","journal-title":"Free Radic Biol Med."},{"key":"B37","doi-asserted-by":"publisher","first-page":"354","DOI":"10.1016\/j.foodchem.2018.09.135","article-title":"Structure-antioxidant capacity relationship of dihydrochalcone compounds in Malus.","volume":"275","author":"Wang","year":"2019","journal-title":"Food Chem."},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.3390\/molecules26247557","article-title":"Green extraction of antioxidant flavonoids from pigeon pea (Cajanus cajan (L.) Millsp.) seeds and its antioxidant potentials using ultrasound-assisted methodology.","volume":"26","author":"Tungmunnithum","year":"2021","journal-title":"Molecules."},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1007\/s11130-015-0497-2","article-title":"Components of flavonodis and antioxidant activity analysis of exctracts from red-flesh apple peel.","volume":"52","author":"Xiang","year":"2016","journal-title":"J Plant Physiol."},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1128\/Spectrum.00484-21","article-title":"The protective effects of live and pasteurized Akkermansia muciniphila and its extracellular vesicles against HFD\/CCl4-induced liver injury.","volume":"9","author":"Keshavarz Azizi Raftar","year":"2021","journal-title":"Microbiol Spectr."},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-09673-5","article-title":"Quercetin prevents hepatic fibrosis by inhibiting hepatic stellate cell activation and reducing autophagy via the TGF-\u03b21\/Smads and PI3K\/Akt pathways.","volume":"7","author":"Wu","year":"2017","journal-title":"Sci Rep."},{"key":"B42","doi-asserted-by":"publisher","first-page":"558","DOI":"10.1016\/j.jhep.2019.10.003","article-title":"The gut-liver axis in liver disease: pathophysiological basis for therapy.","volume":"72","author":"Albillos","year":"2020","journal-title":"J Hepatol."},{"key":"B43","doi-asserted-by":"publisher","first-page":"1230","DOI":"10.1007\/s43440-021-00227-1","article-title":"Pharmacological properties of baicalin on liver diseases: a narrative review.","volume":"73","author":"Yang","year":"2021","journal-title":"Pharmacol Rep."},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.3390\/molecules23081952","article-title":"Flavonoids, sterols and lignans from cochlospermum vitifolium and their relationship with its liver activity.","volume":"23","author":"Aguilar-Guadarrama","year":"2018","journal-title":"Molecules."},{"key":"B45","doi-asserted-by":"publisher","first-page":"3321","DOI":"10.1039\/c8fo00525g","article-title":"Granny Smith apple procyanidin extract upregulates tight junction protein expression and modulates oxidative stress and inflammation in lipopolysaccharide-induced Caco-2 cells.","volume":"9","author":"Wu","year":"2018","journal-title":"Food Funct."},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.3390\/ijms19092785","article-title":"Molecular mechanism and health role of functional ingredients in blueberry for chronic disease in human beings.","volume":"19","author":"Ma","year":"2018","journal-title":"Int J Mol Sci."},{"key":"B47","doi-asserted-by":"publisher","first-page":"5938","DOI":"10.1021\/acs.jafc.1c01851","article-title":"Efficient preparation of black tea extract (BTE) with the high content of theaflavin mono- and digallates and the protective effects of BTE on CCl4-induced rat liver and renal injury.","volume":"69","author":"Zhan","year":"2021","journal-title":"J Agric Food Chem."},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.3390\/foods10020267","article-title":"Profiling of phenolic compounds and triterpene acids of twelve apple (Malus domestica Borkh.) cultivars.","volume":"10","author":"Gean\u00e3","year":"2021","journal-title":"Foods."},{"key":"B49","doi-asserted-by":"publisher","first-page":"390","DOI":"10.3390\/molecules17010390","article-title":"Variations of antioxidant characteristics and mineral contents in pulp and peel of different apple (Malus domestica Borkh.) cultivars from Pakistan.","volume":"17","author":"Manzoor","year":"2012","journal-title":"Molecules."},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22052261","article-title":"Cyanidin 3-O-galactoside: a natural compound with multiple health benefits.","volume":"22","author":"Liang","year":"2021","journal-title":"Int J Mol Sci."},{"key":"B51","doi-asserted-by":"publisher","first-page":"38","DOI":"10.3109\/13880209.2010.493179","article-title":"Protective effects of baicalin on carbon tetrachloride induced liver injury by activating PPARgamma and inhibiting TGFbeta1.","volume":"49","author":"Qiao","year":"2011","journal-title":"Pharm Biol."},{"key":"B52","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1016\/j.etp.2011.08.005","article-title":"Baicalin prevents cadmium induced hepatic cytotoxicity, oxidative stress and histomorphometric alterations.","volume":"65","author":"Wen","year":"2013","journal-title":"Exp Toxicol Pathol."},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2020.111121","article-title":"Puerariae Lobatae radix flavonoids and puerarin alleviate alcoholic liver injury in zebrafish by regulating alcohol and lipid metabolism.","volume":"134","author":"Liu","year":"2021","journal-title":"Biomed Pharmacother."},{"key":"B54","doi-asserted-by":"publisher","first-page":"1264","DOI":"10.1080\/13880209.2022.2086584","article-title":"Anti-liver fibrosis effects of the total flavonoids of litchi semen on CCl4-induced liver fibrosis in rats associated with the upregulation of retinol metabolism.","volume":"60","author":"Yan","year":"2022","journal-title":"Pharm Biol."},{"key":"B55","doi-asserted-by":"publisher","first-page":"3312","DOI":"10.1021\/acs.jafc.0c06815","article-title":"Gut microbiota modulation by polyphenols from Aronia melanocarpa of LPS-induced liver diseases in rats.","volume":"69","author":"Kong","year":"2021","journal-title":"J Agric Food Chem."},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1016\/j.fct.2019.110751","article-title":"Chlorogenic acid attenuates cadmium-induced intestinal injury in Sprague-Dawley rats.","volume":"133","author":"Xue","year":"2019","journal-title":"Food Chem Toxicol."},{"key":"B57","doi-asserted-by":"publisher","first-page":"367","DOI":"10.1007\/s11154-020-09622-0","article-title":"Polyphenols and their anti-obesity role mediated by the gut microbiota: a comprehensive review.","volume":"22","author":"Duarte","year":"2021","journal-title":"Rev Endocr Metab Disord."},{"key":"B58","doi-asserted-by":"publisher","first-page":"815","DOI":"10.1080\/22221751.2022.2045876","article-title":"Metformin attenuated sepsis-related liver injury by modulating gut microbiota.","volume":"11","author":"Liang","year":"2022","journal-title":"Emerg Microbes Infect."},{"key":"B59","doi-asserted-by":"publisher","first-page":"209","DOI":"10.1093\/jn\/nxx027","article-title":"Blueberry supplementation influences the gut microbiota, inflammation, and insulin resistance in high-fat-diet-fed rats.","volume":"148","author":"Lee","year":"2018","journal-title":"J Nutr."},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1016\/j.jff.2020.104332","article-title":"Smilax china L. polyphenols alleviates obesity and inflammation by modulating gut microbiota in high fat\/high sucrose diet-fed C57BL\/6J mice.","volume":"77","author":"Li","year":"2021","journal-title":"J Funct Foods."}],"container-title":["Frontiers in Nutrition"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnut.2022.1098954\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,18]],"date-time":"2023-01-18T11:57:03Z","timestamp":1674043023000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnut.2022.1098954\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,1,18]]},"references-count":60,"alternative-id":["10.3389\/fnut.2022.1098954"],"URL":"https:\/\/doi.org\/10.3389\/fnut.2022.1098954","relation":{},"ISSN":["2296-861X"],"issn-type":[{"value":"2296-861X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,1,18]]},"article-number":"1098954"}}