{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,30]],"date-time":"2026-05-30T15:02:09Z","timestamp":1780153329422,"version":"3.54.0"},"reference-count":38,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T00:00:00Z","timestamp":1778803200000},"content-version":"vor","delay-in-days":115,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Shenzhen Medical Research Fund","award":["D250402006"],"award-info":[{"award-number":["D250402006"]}]},{"name":"Shenzhen Medical Research Fund","award":["A2503081"],"award-info":[{"award-number":["A2503081"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,1,20]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Constipation is a common digestive disorder in the elderly caused by weakened intestinal peristalsis and reduced mucus secretion that significantly impacts quality of life. Current treatments typically provide only temporary symptomatic relief and may lead to dependence and adverse effects.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This study investigated the therapeutic effects of a modified traditional Chinese formula, modified Zengye decoction (MZD) on age-related constipation by modulating the gut microbiome and metabolomics. Aged constipated rats were gavage-fed with or without MZD. After detection of the indicators related to the disease, the microbial and metabolic profiles were generated for all the fecal samples by using 16S rRNA gene sequencing and 1H nuclear magnetic resonance (1H NMR) spectroscopy, respectively.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>MZD effectively alleviated constipation symptoms in aged mice by enhancing the intestinal peristalsis and antioxidant capacity. Gut microbiome analysis revealed that MZD significantly altered the abundance of Firmicutes, Bacteroidetes, and Actinobacteria. Specifically, the abundance of beneficial bacteria such as Corynebacterium, Roseburia, and Clostridium increased by 6-fold, 4-fold, and 3-fold, respectively. These changes in microbial composition enhanced the production of short-chain fatty acids (SCFAs), including acetate, propionate, and butyrate. Additionally, MZD significantly increased the expression of Mucin 2 protein and the moisture content of the small intestine, while decreasing pro-inflammatory cytokines such as tumor necrosis factor-alpha, interleukin-1 beta, and interleukin-6, and increasing anti-inflammatory interleukin-10, which may be attributed to the elevated levels of SCFAs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>By effectively regulating the gut microbiome and SCFA metabolism, MZD demonstrated significant anti-inflammatory and mucus-secretion-promoting effects, showing therapeutic potential for age-related constipation, enteritis, and other inflammation-related intestinal diseases.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/gastro\/goag031","type":"journal-article","created":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T12:50:54Z","timestamp":1773838254000},"source":"Crossref","is-referenced-by-count":0,"title":["Effect of modified Zengye decoction on age-related constipation\n                    <i>via<\/i>\n                    modulation of the host\u2013microbial metabolic axis"],"prefix":"10.1093","volume":"14","author":[{"given":"Deliang","family":"Liu","sequence":"first","affiliation":[{"name":"National Clinical Research Center for Infectious Diseases, Shenzhen Third People\u2019s Hospital, Southern University of Science and Technology , Shenzhen, Guangdong 518112, P. R.","place":["China"]},{"name":"Institute for Hepatology, Shenzhen Third People\u2019s Hospital , Shenzhen, Guangdong 518112, P. R.","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuying","family":"Chen","sequence":"additional","affiliation":[{"name":"National Clinical Research Center for Infectious Diseases, Shenzhen Third People\u2019s Hospital, Southern University of Science and Technology , Shenzhen, Guangdong 518112, P. R.","place":["China"]},{"name":"The Affiliated Dongguan Songshan Lake Central Hospital, Guangdong Medical University , Dongguan, Guangdong 523808, P. R.","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinzhi","family":"Pan","sequence":"additional","affiliation":[{"name":"National Clinical Research Center for Infectious Diseases, Shenzhen Third People\u2019s Hospital, Southern University of Science and Technology , Shenzhen, Guangdong 518112, P. R.","place":["China"]},{"name":"The Affiliated Dongguan Songshan Lake Central Hospital, Guangdong Medical University , Dongguan, Guangdong 523808, P. R.","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhuojun","family":"He","sequence":"additional","affiliation":[{"name":"National Clinical Research Center for Infectious Diseases, Shenzhen Third People\u2019s Hospital, Southern University of Science and Technology , Shenzhen, Guangdong 518112, P. R.","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Zhou","sequence":"additional","affiliation":[{"name":"National Clinical Research Center for Infectious Diseases, Shenzhen Third People\u2019s Hospital, Southern University of Science and Technology , Shenzhen, Guangdong 518112, P. R.","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guiqin","family":"Dai","sequence":"additional","affiliation":[{"name":"National Clinical Research Center for Infectious Diseases, Shenzhen Third People\u2019s Hospital, Southern University of Science and Technology , Shenzhen, Guangdong 518112, P. R.","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiafei","family":"Dai","sequence":"additional","affiliation":[{"name":"National Clinical Research Center for Infectious Diseases, Shenzhen Third People\u2019s Hospital, Southern University of Science and Technology , Shenzhen, Guangdong 518112, P. R.","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiqiang","family":"Lin","sequence":"additional","affiliation":[{"name":"National Clinical Research Center for Infectious Diseases, Shenzhen Third People\u2019s Hospital, Southern University of Science and Technology , Shenzhen, Guangdong 518112, P. R.","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pengfei","family":"Zhao","sequence":"additional","affiliation":[{"name":"Institute for Hepatology, Shenzhen Third People\u2019s Hospital , Shenzhen, Guangdong 518112, P. R.","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8308-5534","authenticated-orcid":false,"given":"Hongzhou","family":"Lu","sequence":"additional","affiliation":[{"name":"Guangdong Key Lab for Diagnosis & Treatment of Emerging Infectious Diseases, Shenzhen Third People\u2019s Hospital , Shenzhen, Guangdong 518112, P. R.","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0463-7968","authenticated-orcid":false,"given":"Mingbin","family":"Zheng","sequence":"additional","affiliation":[{"name":"National Clinical Research Center for Infectious Diseases, Shenzhen Third People\u2019s Hospital, Southern University of Science and Technology , Shenzhen, Guangdong 518112, P. R.","place":["China"]},{"name":"The Affiliated Dongguan Songshan Lake Central Hospital, Guangdong Medical University , Dongguan, Guangdong 523808, P. R.","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,5,13]]},"reference":[{"key":"2026053010375236300_goag031-B1","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1186\/s12876-024-03384-8","article-title":"The associations between modifiable risk factors and constipation: a comprehensive mendelian randomization study","volume":"24","author":"Chang","year":"2024","journal-title":"BMC Gastroenterol"},{"key":"2026053010375236300_goag031-B2","doi-asserted-by":"crossref","first-page":"423","DOI":"10.3389\/fcimb.2020.00423","article-title":"Lactobacillus rhamnosus strains relieve loperamide-induced constipation via different pathways independent of short-Chain fatty acids","volume":"10","author":"Wang","year":"2020","journal-title":"Front Cell Infect Microbiol"},{"key":"2026053010375236300_goag031-B3","doi-asserted-by":"crossref","first-page":"894216","DOI":"10.3389\/fcimb.2022.894216","article-title":"Bifidobacterium treated by electrostatic spray drying relieved constipation by changing the relative abundance of bacteria associated with gastrointestinal regulatory peptides","volume":"12","author":"Jiang","year":"2022","journal-title":"Front Cell Infect Microbiol"},{"key":"2026053010375236300_goag031-B4","doi-asserted-by":"crossref","first-page":"737713","DOI":"10.3389\/fmed.2021.737713","article-title":"Microbial profiles of patients with antipsychotic-related constipation treated with electroacupuncture","volume":"8","author":"Zheng","year":"2021","journal-title":"Front Med (Lausanne)"},{"key":"2026053010375236300_goag031-B5","doi-asserted-by":"crossref","first-page":"930638","DOI":"10.3389\/fphar.2022.930638","article-title":"Therapeutic effect of modified zengye decoction on primary Sjogren\u2019s syndrome and its effect on plasma exosomal proteins","volume":"13","author":"Zeng","year":"2022","journal-title":"Front Pharmacol"},{"key":"2026053010375236300_goag031-B6","first-page":"18876","article-title":"Zengye decoction regulated the expression of aquaporin in colon tissue of rats with constipation through miR-10a-5p targeting Drd2\/AC\/cAMP axis","volume":"21","author":"Chen","year":"2025","journal-title":"Histol Histopathol"},{"key":"2026053010375236300_goag031-B7","doi-asserted-by":"crossref","first-page":"1588786","DOI":"10.1155\/2022\/1588786","article-title":"Zengye decoction attenuated severe acute pancreatitis complicated with acute kidney injury by modulating the gut microbiome and serum amino acid metabolome","volume":"2022","author":"Dai","year":"2022","journal-title":"Evid Based Complement Alternat Med"},{"key":"2026053010375236300_goag031-B8","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1089\/rej.2019.2228","article-title":"Zengye decoction ameliorates insulin resistance by promoting glucose uptake","volume":"23","author":"Wang","year":"2020","journal-title":"Rejuvenation Res"},{"key":"2026053010375236300_goag031-B9","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/j.jchromb.2017.12.019","article-title":"Putative identification of components in Zengye decoction and their effects on glucose consumption and lipogenesis in insulin-induced insulin-resistant HepG2 cells","volume":"1073","author":"Liu","year":"2018","journal-title":"J Chromatogr B Analyt Technol Biomed Life Sci"},{"key":"2026053010375236300_goag031-B10","doi-asserted-by":"crossref","first-page":"1361","DOI":"10.1016\/j.biopha.2018.11.013","article-title":"Zengye decoction induces alterations to metabolically active gut microbiota in aged constipated rats","volume":"109","author":"Liu","year":"2019","journal-title":"Biomed Pharmacother"},{"key":"2026053010375236300_goag031-B11","doi-asserted-by":"crossref","first-page":"48136","DOI":"10.1039\/C7RA07651G","article-title":"Study on alterations of physiological functions in aged constipation rats with fluid-deficiency based on metabonomic and microbiology analysis","volume":"7","author":"Liu","year":"2017","journal-title":"RSC Adv"},{"key":"2026053010375236300_goag031-B12","doi-asserted-by":"crossref","first-page":"3193","DOI":"10.1016\/j.apsb.2021.05.017","article-title":"Ligand-based substituent-anchoring design of selective receptor-interacting protein kinase 1 necroptosis inhibitors for ulcerative colitis therapy","volume":"11","author":"Zhu","year":"2021","journal-title":"Acta Pharm Sin B"},{"key":"2026053010375236300_goag031-B13","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1093\/bioinformatics\/btp636","article-title":"PyNAST: a flexible tool for aligning sequences to a template alignment","volume":"26","author":"Caporaso","year":"2010","journal-title":"Bioinformatics"},{"key":"2026053010375236300_goag031-B14","doi-asserted-by":"crossref","first-page":"1023","DOI":"10.1039\/b927543f","article-title":"An optimised sample preparation method for NMR-based faecal metabonomic analysis","volume":"135","author":"Wu","year":"2010","journal-title":"Analyst"},{"key":"2026053010375236300_goag031-B15","doi-asserted-by":"crossref","first-page":"2958","DOI":"10.1021\/pr4002383","article-title":"Systemic responses of mice to dextran sulfate sodium-induced acute ulcerative colitis using 1H NMR spectroscopy","volume":"12","author":"Dong","year":"2013","journal-title":"J Proteome Res"},{"key":"2026053010375236300_goag031-B16","doi-asserted-by":"crossref","first-page":"2692","DOI":"10.1038\/nprot.2007.376","article-title":"Metabolic profiling, metabolomic and metabonomic procedures for NMR spectroscopy of urine, plasma, serum and tissue extracts","volume":"2","author":"Beckonert","year":"2007","journal-title":"Nat Protoc"},{"key":"2026053010375236300_goag031-B17","doi-asserted-by":"crossref","first-page":"4208","DOI":"10.1021\/pr2003598","article-title":"Metabolomics of fecal extracts detects altered metabolic activity of gut microbiota in ulcerative colitis and irritable bowel syndrome","volume":"10","author":"Le Gall","year":"2011","journal-title":"J Proteome Res"},{"key":"2026053010375236300_goag031-B18","doi-asserted-by":"crossref","first-page":"e01202","DOI":"10.7554\/eLife.01202","article-title":"Expansion of intestinal Prevotella copri correlates with enhanced susceptibility to arthritis","volume":"2","author":"Scher","year":"2013","journal-title":"Elife"},{"key":"2026053010375236300_goag031-B19","doi-asserted-by":"crossref","first-page":"E4485","DOI":"10.1073\/pnas.1415174111","article-title":"Intestinal permeability, gut-bacterial dysbiosis, and behavioral markers of alcohol-dependence severity","volume":"111","author":"Leclercq","year":"2014","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2026053010375236300_goag031-B20","doi-asserted-by":"crossref","first-page":"986562","DOI":"10.3389\/fvets.2022.986562","article-title":"Sodium humate alters the intestinal microbiome, short-chain fatty acids, eggshell ultrastructure, and egg performance of old laying hens","volume":"9","author":"Li","year":"2022","journal-title":"Front Vet Sci"},{"key":"2026053010375236300_goag031-B21","doi-asserted-by":"crossref","first-page":"2420765","DOI":"10.1080\/19490976.2024.2420765","article-title":"How important are fatty acids in human health and can they be used in treating diseases?","volume":"16","author":"Dicks","year":"2024","journal-title":"Gut Microbes"},{"key":"2026053010375236300_goag031-B22","doi-asserted-by":"crossref","first-page":"3658","DOI":"10.1021\/acs.jafc.0c07637","article-title":"Effect of blueberry anthocyanin-rich extracts on peripheral and hippocampal antioxidant defensiveness: the analysis of the serum fatty acid species and gut microbiota profile","volume":"69","author":"Si","year":"2021","journal-title":"J Agric Food Chem"},{"key":"2026053010375236300_goag031-B23","doi-asserted-by":"crossref","first-page":"155056","DOI":"10.1016\/j.phymed.2023.155056","article-title":"Paeonol alleviates ulcerative colitis in mice by increasing short-chain fatty acids derived from Clostridium butyricum","volume":"120","author":"Zhao","year":"2023","journal-title":"Phytomedicine"},{"key":"2026053010375236300_goag031-B24","doi-asserted-by":"crossref","first-page":"7751","DOI":"10.3390\/ijms23147751","article-title":"Molecular effects of chronic exposure to palmitate in intestinal organoids: a new model to study obesity and diabetes","volume":"23","author":"Filippello","year":"2022","journal-title":"Int J Mol Sci"},{"key":"2026053010375236300_goag031-B25","doi-asserted-by":"crossref","first-page":"636194","DOI":"10.1155\/2013\/636194","article-title":"A review of the phytochemistry and pharmacological activities of raphani semen","volume":"2013","author":"Sham","year":"2013","journal-title":"Evid Based Complement Alternat Med"},{"key":"2026053010375236300_goag031-B26","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1142\/S0192415X2250029X","article-title":"Herbal medicines for constipation and phytochemical comparison of active components","volume":"50","author":"Ma","year":"2022","journal-title":"Am J Chin Med"},{"key":"2026053010375236300_goag031-B27","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1016\/j.phymed.2013.08.013","article-title":"Effects of ophiopogonin D and spicatoside a derived from liriope tuber on secretion and production of mucin from airway epithelial cells","volume":"21","author":"Park","year":"2014","journal-title":"Phytomedicine"},{"key":"2026053010375236300_goag031-B28","doi-asserted-by":"crossref","first-page":"7734","DOI":"10.3390\/molecules27227734","article-title":"Phytochemistry, medicinal properties, bioactive compounds, and therapeutic potential of the genus eremophila (Scrophulariaceae)","volume":"27","author":"Cock","year":"2022","journal-title":"Molecules"},{"key":"2026053010375236300_goag031-B29","doi-asserted-by":"crossref","first-page":"1691","DOI":"10.3390\/molecules29081691","article-title":"The antioxidant action of astragali radix: its active components and molecular basis","volume":"29","author":"Yao","year":"2024","journal-title":"Molecules"},{"key":"2026053010375236300_goag031-B30","doi-asserted-by":"crossref","first-page":"19","DOI":"10.3389\/fmed.2019.00019","article-title":"Gut microbiota and chronic constipation: a review and update","volume":"6","author":"Ohkusa","year":"2019","journal-title":"Front Med (Lausanne)"},{"key":"2026053010375236300_goag031-B31","doi-asserted-by":"crossref","first-page":"118761","DOI":"10.1016\/j.carbpol.2021.118761","article-title":"Bamboo shavings derived O-acetylated xylan alleviates loperamide-induced constipation in mice","volume":"276","author":"Huang","year":"2022","journal-title":"Carbohydr Polym"},{"key":"2026053010375236300_goag031-B32","doi-asserted-by":"crossref","first-page":"e2306297","DOI":"10.1002\/advs.202306297","article-title":"Gastrointestinal dysmotility predisposes to colitis through regulation of gut microbial composition and linoleic acid metabolism","volume":"11","author":"Zhang","year":"2024","journal-title":"Adv Sci (Weinh)"},{"key":"2026053010375236300_goag031-B33","doi-asserted-by":"crossref","first-page":"1221","DOI":"10.1136\/gut.28.10.1221","article-title":"Short chain fatty acids in human large intestine, portal, hepatic and venous blood","volume":"28","author":"Cummings","year":"1987","journal-title":"Gut"},{"key":"2026053010375236300_goag031-B34","doi-asserted-by":"crossref","first-page":"660","DOI":"10.5551\/jat.RV17006","article-title":"Are short chain fatty acids in gut microbiota defensive players for inflammation and atherosclerosis?","volume":"24","author":"Ohira","year":"2017","journal-title":"J Atheroscler Thromb"},{"key":"2026053010375236300_goag031-B35","doi-asserted-by":"crossref","first-page":"1214","DOI":"10.3390\/ijms20051214","article-title":"Secondary bile acids and short chain fatty acids in the colon: a focus on colonic microbiome, cell proliferation, inflammation, and cancer","volume":"20","author":"Zeng","year":"2019","journal-title":"Int J Mol Sci"},{"key":"2026053010375236300_goag031-B36","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1186\/s40168-017-0246-x","article-title":"Microbiome and metabolome modifying effects of several cardiovascular disease interventions in apo-E\u2212\/\u2212 mice","volume":"5","author":"Ryan","year":"2017","journal-title":"Microbiome"},{"key":"2026053010375236300_goag031-B37","doi-asserted-by":"crossref","first-page":"225","DOI":"10.3748\/wjg.v30.i3.225","article-title":"Relationship among Parkinson\u2019s disease, constipation, microbes, and microbiological therapy","volume":"30","author":"Yuan","year":"2024","journal-title":"World J Gastroenterol"},{"key":"2026053010375236300_goag031-B38","doi-asserted-by":"crossref","first-page":"2254","DOI":"10.1007\/BF02071409","article-title":"Treatment of distal ulcerative colitis with short-chain fatty acid enemas. A placebo-controlled trial. German-Austrian SCFA study group","volume":"41","author":"Scheppach","year":"1996","journal-title":"Dig Dis Sci"}],"container-title":["Gastroenterology Report"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/gastro\/article-pdf\/doi\/10.1093\/gastro\/goag031\/68289832\/goag031.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/gastro\/article-pdf\/doi\/10.1093\/gastro\/goag031\/68289832\/goag031.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,30]],"date-time":"2026-05-30T14:38:04Z","timestamp":1780151884000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/gastro\/article\/doi\/10.1093\/gastro\/goag031\/8678589"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,20]]},"references-count":38,"URL":"https:\/\/doi.org\/10.1093\/gastro\/goag031","relation":{},"ISSN":["2052-0034"],"issn-type":[{"value":"2052-0034","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,2]]},"published":{"date-parts":[[2026,1,20]]},"article-number":"goag031"}}