{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T20:13:19Z","timestamp":1792872799194,"version":"4.5.0"},"reference-count":48,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2023,7,1]],"date-time":"2023-07-01T00:00:00Z","timestamp":1688169600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2023,7,1]],"date-time":"2023-07-01T00:00:00Z","timestamp":1688169600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2023,5,18]],"date-time":"2023-05-18T00:00:00Z","timestamp":1684368000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Experimental Gerontology"],"published-print":{"date-parts":[[2023,7]]},"DOI":"10.1016\/j.exger.2023.112216","type":"journal-article","created":{"date-parts":[[2023,5,31]],"date-time":"2023-05-31T01:23:03Z","timestamp":1685496183000},"page":"112216","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":5,"special_numbering":"C","title":["Comprehensive microbiomes and fecal metabolomics combined with network pharmacology reveal the effects of Jichuanjian on aged functional constipation"],"prefix":"10.1016","volume":"178","author":[{"given":"Xiaojie","family":"Liu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziyu","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Di","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sijun","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuemei","family":"Qin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.exger.2023.112216_bb0005","doi-asserted-by":"crossref","DOI":"10.3389\/fphar.2021.672054","article-title":"Therapeutic effects of naringin in rheumatoid arthritis: network pharmacology and experimental validation","volume":"12","author":"Aihaiti","year":"2021","journal-title":"Front. Pharmacol."},{"issue":"7","key":"10.1016\/j.exger.2023.112216_bb0010","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1002\/iub.1756","article-title":"The glutathione cycle: glutathione metabolism beyond the \u03b3-glutamyl cycle","volume":"70","author":"Bachhawat","year":"2018","journal-title":"IUBMB Life"},{"key":"10.1016\/j.exger.2023.112216_bb0015","first-page":"244","article-title":"The effects of enteral supplementation of glutamine and arginine in lipopolysaccharide (LPS) induced sepsis","volume":"21","author":"Bakir","year":"2019","journal-title":"Prog. Nutr."},{"issue":"9","key":"10.1016\/j.exger.2023.112216_bb0020","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1016\/j.tcb.2019.05.005","article-title":"Acetate metabolism in physiology, cancer, and beyond","volume":"29","author":"Bose","year":"2019","journal-title":"Trends Cell Biol."},{"key":"10.1016\/j.exger.2023.112216_bb0025","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1016\/j.exger.2013.10.010","article-title":"Fecal and urinary NMR-based metabolomics unveil an aging signature in mice","volume":"49","author":"Calvani","year":"2014","journal-title":"Exp. Gerontol."},{"issue":"8","key":"10.1016\/j.exger.2023.112216_bb0030","doi-asserted-by":"crossref","first-page":"1103","DOI":"10.1007\/s00726-019-02757-8","article-title":"Regulation of arginine biosynthesis, catabolism and transport in Escherichia coli","volume":"51","author":"Charlier","year":"2019","journal-title":"Amino Acids"},{"key":"10.1016\/j.exger.2023.112216_bb0035","doi-asserted-by":"crossref","first-page":"890","DOI":"10.1016\/j.ijbiomac.2019.11.047","article-title":"Intake of Ganoderma lucidum polysaccharides reverses the disturbed gut microbiota and metabolism in type 2 diabetic rats","volume":"155","author":"Chen","year":"2019","journal-title":"Int. J. Biol. Macromol."},{"key":"10.1016\/j.exger.2023.112216_bb0040","article-title":"Prevalence and risk factors of functional constipation according to the Rome criteria in China: a systematic review and meta-analysis","volume":"9","author":"Chen","year":"2022","journal-title":"Front. Med (Lausanne)."},{"issue":"39","key":"10.1016\/j.exger.2023.112216_bb0045","doi-asserted-by":"crossref","first-page":"4886","DOI":"10.3748\/wjg.15.4886","article-title":"Systematic review of Chinese herbal medicine for functional constipation","volume":"15","author":"Cheng","year":"2009","journal-title":"World J. Gastroenterol."},{"issue":"7","key":"10.1016\/j.exger.2023.112216_bb0050","doi-asserted-by":"crossref","first-page":"777","DOI":"10.3346\/jkms.2012.27.7.777","article-title":"Methionine enhances the contractile activity of human colon circular smooth muscle in vitro","volume":"27","author":"Choe","year":"2012","journal-title":"J. Korean Med. Sci."},{"key":"10.1016\/j.exger.2023.112216_bb0055","doi-asserted-by":"crossref","first-page":"7767","DOI":"10.1128\/AEM.01477-07","article-title":"Intestinal integrity and Akkermansia muciniphila, a mucin-degrading member of the intestinal microbiota present in infants, adults, and the elderly","volume":"73","author":"Collado","year":"2007","journal-title":"Appl. Environ. Microbiol."},{"key":"10.1016\/j.exger.2023.112216_bb0060","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.jpba.2016.09.044","article-title":"NMR-based metabonomics and correlation analysis reveal potential biomarkers associated with chronic atrophic gastritis","volume":"132","author":"Cui","year":"2017","journal-title":"J. Pharm. Biomed. Anal."},{"issue":"11","key":"10.1016\/j.exger.2023.112216_bb0065","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1007\/s11894-020-00791-1","article-title":"Constipation and fecal incontinence in the elderly","volume":"22","author":"Deb","year":"2020","journal-title":"Curr. Gastroenterol. Rep."},{"issue":"2","key":"10.1016\/j.exger.2023.112216_bb0070","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/0167-4943(89)90033-2","article-title":"Amino acid concentrations in cerebrospinal fluid in presenile and senile dementia of alzheimer type and multi-infarct dementia","volume":"9","author":"Degrell","year":"1989","journal-title":"Arch. Gerontol. Geriatr."},{"key":"10.1016\/j.exger.2023.112216_bb0075","doi-asserted-by":"crossref","first-page":"1646","DOI":"10.1128\/AEM.01226-07","article-title":"The mucin degrader Akkermansia muciniphila is an abundant resident of the human intestinal tract","volume":"74","author":"Derrien","year":"2008","journal-title":"Appl. Environ. Microbiol."},{"issue":"4","key":"10.1016\/j.exger.2023.112216_bb0080","doi-asserted-by":"crossref","first-page":"1075","DOI":"10.3945\/ajcn.114.089151","article-title":"The effect of probiotics on functional constipation in adults: a systematic review and meta-analysis of randomized controlled trials","volume":"100","author":"Dimidi","year":"2014","journal-title":"Am. J. Clin. Nutr."},{"issue":"6","key":"10.1016\/j.exger.2023.112216_bb0085","doi-asserted-by":"crossref","first-page":"1777","DOI":"10.3390\/nu12061777","article-title":"Chronic supplementation with a mix of salvia officinalis and salvia lavandulaefolia improves Morris Water Maze learning in normal adult C57Bl\/6J mice","volume":"12","author":"Dinel","year":"2020","journal-title":"Nutrients"},{"issue":"7","key":"10.1016\/j.exger.2023.112216_bb0090","doi-asserted-by":"crossref","first-page":"936","DOI":"10.1007\/s11864-022-00976-y","article-title":"Constipation in cancer patients - an update of clinical evidence","volume":"23","author":"Dzierzanowski","year":"2022","journal-title":"Curr. Treat. Options in Oncol."},{"issue":"9","key":"10.1016\/j.exger.2023.112216_bb0095","doi-asserted-by":"crossref","first-page":"2140","DOI":"10.3390\/molecules23092140","article-title":"Characterization of the in vivo and in vitro metabolites of linarin in rat biosamples and intestinal flora using ultra-high performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry","volume":"23","author":"Feng","year":"2018","journal-title":"Molecules"},{"key":"10.1016\/j.exger.2023.112216_bb0100","doi-asserted-by":"crossref","DOI":"10.1016\/j.phrs.2019.104312","article-title":"Lactobacillus sp. improved microbiota and metabolite profiles of aging rats","volume":"146","author":"Hor","year":"2019","journal-title":"Pharmacol. Res."},{"issue":"5","key":"10.1016\/j.exger.2023.112216_bb0105","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1111\/j.1753-4887.2011.00388.x","article-title":"Propionate as a health-promoting microbial metabolite in the human gut","volume":"69","author":"Hosseini","year":"2011","journal-title":"Nutr. Rev."},{"issue":"2","key":"10.1016\/j.exger.2023.112216_bb0110","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1053\/j.gastro.2019.04.022","article-title":"Effects of serotonin and slow-release 5-hydroxytryptophan on gastrointestinal motility in a mouse model of depression","volume":"157","author":"Israelyan","year":"2019","journal-title":"Gastroenterology"},{"issue":"1","key":"10.1016\/j.exger.2023.112216_bb0115","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1111\/prd.12126","article-title":"The aging population: demographics and the biology of aging","volume":"72","author":"Kanasi","year":"2016","journal-title":"Periodontol. 2000"},{"issue":"11","key":"10.1016\/j.exger.2023.112216_bb0120","first-page":"679","article-title":"Constipation\u2014modern laxative therapy","volume":"11","author":"Klaschik","year":"2003","journal-title":"Support Care Cancer"},{"issue":"3","key":"10.1016\/j.exger.2023.112216_bb0125","first-page":"263","article-title":"Diabetic gastroenteropathy: a complication of diabetes mellitus","volume":"51","author":"Kurniawan","year":"2019","journal-title":"Acta Med. Indones."},{"key":"10.1016\/j.exger.2023.112216_bb0130","doi-asserted-by":"crossref","DOI":"10.1016\/j.arr.2020.101198","article-title":"Branched chain amino acids, aging and age-related health","volume":"64","author":"Le Couteur","year":"2020","journal-title":"Ageing Res. Rev."},{"issue":"4","key":"10.1016\/j.exger.2023.112216_bb0135","doi-asserted-by":"crossref","first-page":"2079","DOI":"10.3390\/ijms22042079","article-title":"Dysfunctional gut microbiome networks in childhood IgE-mediated food allergy","volume":"22","author":"Lee","year":"2021","journal-title":"Int. J. Mol. Sci."},{"issue":"6","key":"10.1016\/j.exger.2023.112216_bb0140","doi-asserted-by":"crossref","first-page":"1186","DOI":"10.1002\/jimd.12295","article-title":"Regulation of glycine metabolism by the glycine cleavage system and conjugation pathway in mouse models of non-ketotic hyperglycinemia","volume":"43","author":"Leung","year":"2020","journal-title":"J. Inherit. Metab. Dis."},{"key":"10.1016\/j.exger.2023.112216_bb0145","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.brainresbull.2017.09.009","article-title":"Enriched environment combined with fluoxetine ameliorates depression-like behaviors and hippocampal SYP expression in a rat CUS model","volume":"135","author":"Liu","year":"2017","journal-title":"Brain Res. Bull."},{"issue":"3","key":"10.1016\/j.exger.2023.112216_bb0150","doi-asserted-by":"crossref","first-page":"3798","DOI":"10.18632\/aging.202340","article-title":"Deciphering the correlations between aging and constipation by metabolomics and network pharmacology","volume":"13","author":"Liu","year":"2021","journal-title":"Aging (Albany NY)"},{"issue":"9","key":"10.1016\/j.exger.2023.112216_bb0155","doi-asserted-by":"crossref","first-page":"2197","DOI":"10.3390\/molecules23092197","article-title":"Resveratrol and depression in animal models: a systematic review of the biological mechanisms","volume":"23","author":"Moore","year":"2018","journal-title":"Molecules"},{"key":"10.1016\/j.exger.2023.112216_bb0160","doi-asserted-by":"crossref","DOI":"10.3389\/fphar.2021.619288","article-title":"Analysis of antidepressant activity of huang-lian jie-du decoction through network pharmacology and metabolomics","volume":"12","author":"Qu","year":"2021","journal-title":"Front. Pharmacol."},{"issue":"22","key":"10.1016\/j.exger.2023.112216_bb0165","doi-asserted-by":"crossref","first-page":"6034","DOI":"10.1080\/10408398.2021.1895064","article-title":"Recent advances in the therapeutic application of short-chain fatty acids (SCFAs): an updated review","volume":"62","author":"Rauf","year":"2022","journal-title":"Crit. Rev. Food Sci. Nutr."},{"issue":"4","key":"10.1016\/j.exger.2023.112216_bb0170","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0094699","article-title":"Comparison of microbiological, histological, and immunomodulatory parameters in response to treatment with either combination therapy with prednisone and metronidazole or probiotic VSL#3 strains in dogs with idiopathic inflammatory bowel disease","volume":"9","author":"Rossi","year":"2014","journal-title":"PLoS One"},{"key":"10.1016\/j.exger.2023.112216_bb0175","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1186\/1758-2946-6-13","article-title":"TCMSP: a database of systems pharmacology for drug discovery from herbal medicines","volume":"6","author":"Ru","year":"2014","journal-title":"J. Cheminform."},{"issue":"10","key":"10.1016\/j.exger.2023.112216_bb0180","doi-asserted-by":"crossref","first-page":"2247","DOI":"10.1080\/09603123.2021.1952165","article-title":"Effects of 5.8 GHz microwave on hippocampal synaptic plasticity of rats","volume":"32","author":"Rui","year":"2022","journal-title":"Int. J. Environ. Health Res."},{"issue":"8","key":"10.1016\/j.exger.2023.112216_bb0185","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1111\/codi.13314","article-title":"Function and clinical implications of short-chain fatty acids in patients with mixed refractory constipation","volume":"18","author":"Shi","year":"2016","journal-title":"Color. Dis."},{"issue":"8","key":"10.1016\/j.exger.2023.112216_bb0190","first-page":"2025","article-title":"Constipation and colorectal cancer risk: the Fukuoka colorectal cancer study","volume":"12","author":"Tashiro","year":"2012","journal-title":"Asian Pac. J. Cancer Prev."},{"issue":"1\u20132","key":"10.1016\/j.exger.2023.112216_bb0195","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.mad.2008.06.003","article-title":"Inflammation, ageing and cancer","volume":"130","author":"Vastoac","year":"2009","journal-title":"Mech. Ageing Dev."},{"key":"10.1016\/j.exger.2023.112216_bb0200","first-page":"919","article-title":"Epidemiology and management of chronic constipation in elderly patients","volume":"10","author":"Vazquez Roque","year":"2015","journal-title":"Clin. Interv. Aging"},{"key":"10.1016\/j.exger.2023.112216_bb0205","doi-asserted-by":"crossref","DOI":"10.1016\/j.lfs.2020.117612","article-title":"Protective effect of Andrographolide on 5-Fu induced intestinal mucositis by regulating p38 MAPK signaling pathway","volume":"252","author":"Xiang","year":"2020","journal-title":"Life Sci."},{"issue":"1","key":"10.1016\/j.exger.2023.112216_bb0210","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1186\/s13030-022-00237-2","article-title":"Background factors involved in the epidemiology of functional constipation in the Japanese population: a cross-sectional study","volume":"16","author":"Yamamoto","year":"2022","journal-title":"Biopsychosoc. Med."},{"issue":"7","key":"10.1016\/j.exger.2023.112216_bb0215","doi-asserted-by":"crossref","first-page":"1135","DOI":"10.3390\/molecules22071135","article-title":"How can synergism of traditional medicines benefit from network pharmacology?","volume":"22","author":"Yuan","year":"2017","journal-title":"Molecules"},{"issue":"22","key":"10.1016\/j.exger.2023.112216_bb0220","first-page":"169","article-title":"Effect of jichuanjian on gastrointestinal function, serum intestinal neurotransmitters and intestinal flora in elderly with chronic functional constipation","volume":"24","author":"Zhang","year":"2018","journal-title":"Chin. J. Exp. Tradit. Med. Formulae"},{"issue":"1","key":"10.1016\/j.exger.2023.112216_bb0225","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1186\/s13075-018-1600-5","article-title":"Metabolomics approach by 1H NMR spectroscopy of serum reveals progression axes for asymptomatic hyperuricemia and gout","volume":"20","author":"Zhang","year":"2018","journal-title":"Arthritis Res. Ther."},{"key":"10.1016\/j.exger.2023.112216_bb0230","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1186\/1745-6215-14-366","article-title":"Chinese herbal medicine (Ma Zi Ren Wan) for functional constipation: study protocol for a prospective, double-blinded, double-dummy, randomized controlled trial","volume":"14","author":"Zhong","year":"2013","journal-title":"Trials."},{"issue":"1","key":"10.1016\/j.exger.2023.112216_bb0235","doi-asserted-by":"crossref","first-page":"2306","DOI":"10.1038\/s41598-020-58796-9","article-title":"Integrated LC-MS and GC-MS-based untargeted metabolomics studies of the effect of azadirachtin on bactrocera dorsalis larvae","volume":"10","author":"Zhou","year":"2020","journal-title":"Sci. Rep."},{"issue":"7687","key":"10.1016\/j.exger.2023.112216_bb0240","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1038\/nature25172","article-title":"Precision editing of the gut microbiota ameliorates colitis","volume":"553","author":"Zhu","year":"2018","journal-title":"Nature"}],"container-title":["Experimental Gerontology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0531556523001377?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0531556523001377?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T03:51:39Z","timestamp":1759981899000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0531556523001377"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,7]]},"references-count":48,"alternative-id":["S0531556523001377"],"URL":"https:\/\/doi.org\/10.1016\/j.exger.2023.112216","relation":{},"ISSN":["0531-5565"],"issn-type":[{"value":"0531-5565","type":"print"}],"subject":[],"published":{"date-parts":[[2023,7]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Comprehensive microbiomes and fecal metabolomics combined with network pharmacology reveal the effects of Jichuanjian on aged functional constipation","name":"articletitle","label":"Article Title"},{"value":"Experimental Gerontology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.exger.2023.112216","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2023 The Authors. Published by Elsevier Inc.","name":"copyright","label":"Copyright"}],"article-number":"112216"}}