{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T15:28:16Z","timestamp":1791646096885,"version":"4.3.4"},"reference-count":46,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,4,29]],"date-time":"2025-04-29T00:00:00Z","timestamp":1745884800000},"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. Microbiol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>To establish and evaluate an IBS-D mouse model with Spleen-Kidney Yang Deficiency, explore the microecological mechanisms of IBS-D, and provide experimental evidence for the clinical diagnosis and treatment of IBS-D with Spleen-Kidney Yang Deficiency.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      SPF-grade female Kunming mice were used to establish an IBS-D model with Spleen-Kidney Yang Deficiency through\n                      <jats:italic>Folium senna-<\/jats:italic>\n                      adenine administration combined with restraint-clamping tail. (1) Clinical symptoms and signs were assessed using diagnostic criteria. (2) The small intestine structure was examined via Alcian blue staining, and intestinal barrier markers like D-LA (D-lactate) and DAO (diamine oxidase) were measured by ELISA to assess pathophysiological changes. (3) 16S rRNA gene sequencing was performed to analyze the intestinal microbiota.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      (I) The model mice exhibited symptoms of IBS-D with Spleen-Kidney Yang Deficiency. (II) ELISA and alcian blue staining revealed elevated levels of D-LA and DAO activity in the model group, indicating damage to the intestinal mucosal barrier structure. (III) Analysis of the intestinal mucosal microbiota in the model group revealed differences in dominant and characteristic bacteria at various taxonomic levels compared with those in the normal group, reflecting an imbalance in the intestinal mucosal microbiota. (IV)\n                      <jats:italic>Lactobacillus<\/jats:italic>\n                      and\n                      <jats:italic>Lentilactobacillus<\/jats:italic>\n                      are associated with mucosal barrier damage in mice modeled by\n                      <jats:italic>Folium senna-<\/jats:italic>\n                      adenine administration combined with restraint-clamping tail.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      The combination of\n                      <jats:italic>Folium senna-<\/jats:italic>\n                      adenine administration with restraint-clamping tail can be used to successfully establish an IBS-D mouse model with Spleen-Kidney Yang Deficiency. This model leads to damage to the intestinal mucosal structure.\n                      <jats:italic>Streptococcus<\/jats:italic>\n                      ,\n                      <jats:italic>Serratia<\/jats:italic>\n                      ,\n                      <jats:italic>Helicobacter<\/jats:italic>\n                      ,\n                      <jats:italic>Phocaeicola<\/jats:italic>\n                      , and\n                      <jats:italic>Desulfomicrobium<\/jats:italic>\n                      may serve as potential biological markers for the intestinal mucosal microbiota.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmicb.2025.1567971","type":"journal-article","created":{"date-parts":[[2025,4,29]],"date-time":"2025-04-29T01:25:41Z","timestamp":1745889941000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["Association of intestinal mucosal barrier function with intestinal microbiota in Spleen-Kidney Yang Deficiency IBS-D mice"],"prefix":"10.3389","volume":"16","author":[{"given":"Liwen","family":"Li","sequence":"first","affiliation":[{"name":"School of Traditional Chinese Medicine, Hunan University of Chinese Medicine","place":["Changsha, China"]},{"name":"Laboratory of Chinese Medicine Prescription and Syndromes Translational Medicine","place":["Changsha, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Long","sequence":"additional","affiliation":[{"name":"School of Traditional Chinese Medicine, Hunan University of Chinese Medicine","place":["Changsha, China"]},{"name":"Laboratory of Chinese Medicine Prescription and Syndromes Translational Medicine","place":["Changsha, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Na","family":"Deng","sequence":"additional","affiliation":[{"name":"School of Traditional Chinese Medicine, Hunan University of Chinese Medicine","place":["Changsha, China"]},{"name":"Laboratory of Chinese Medicine Prescription and Syndromes Translational Medicine","place":["Changsha, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhoujin","family":"Tan","sequence":"additional","affiliation":[{"name":"School of Traditional Chinese Medicine, Hunan University of Chinese Medicine","place":["Changsha, China"]},{"name":"Laboratory of Chinese Medicine Prescription and Syndromes Translational Medicine","place":["Changsha, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,4,29]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"1948","DOI":"10.13288\/j.11-2166\/r.2024.18.017","article-title":"Expert consensus on the diagnosis and treatment of irritable bowel syndrome in traditional Chinese medicine 2024","volume":"65","author":"Bian","year":"2024","journal-title":"J. Tradit. Chin."},{"key":"ref2","doi-asserted-by":"publisher","first-page":"326","DOI":"10.1016\/j.tips.2010.04.008","article-title":"Current and emerging therapies in irritable bowel syndrome: from pathophysiology to treatment","volume":"31","author":"Chang","year":"2010","journal-title":"Trends Pharmacol. Sci."},{"key":"ref3","article-title":"Clinical study on Wang Kentang Guchang Wan Jiawei in treating IBS-D(Spleen and Kidney Yang Deficiency Syndrome)","author":"Chen","year":"2019"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"1136","DOI":"10.3389\/fmicb.2019.01136","article-title":"The microbiome and irritable bowel syndrome - a review on the pathophysiology, current research and future therapy","volume":"10","author":"Chong","year":"2019","journal-title":"Front. Microbiol."},{"key":"ref5","doi-asserted-by":"publisher","first-page":"2572","DOI":"10.13288\/j.11-2166\/r.2024.24.011","article-title":"Establishment and validation of a mouse model of Spleen-Kidney Yang Deficiency syndrome in irritable bowel syndrome-diarrhea","volume":"65","author":"Deng","year":"2024","journal-title":"J. Tradit. Chin. Med."},{"key":"ref6","doi-asserted-by":"publisher","first-page":"119","DOI":"10.13381\/j.cnki.cjm.201901028","article-title":"The progress of the relationship between intestinal microbiota and diarrhea-predominant irritable bowel syndrome","volume":"31","author":"Ding","year":"2019","journal-title":"Chin. J. Microecol."},{"key":"ref7","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1007\/s13205-024-04180-7","article-title":"Involvement of intestinal mucosal microbiota in adenine-induced liver function injury. 3","volume":"15","author":"Fang","year":"2025","journal-title":"Biotech"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"1806","DOI":"10.3969\/j.issn.1008-0805.2021.08.04","article-title":"Study on dose-time-effect relationship of diarrhea model in young rats induced by folium senna","volume":"32","author":"Guan","year":"2021","journal-title":"Shizhen J. Tradit. Chin. Med. Materia Med"},{"key":"ref9","article-title":"Establishment of IBS-D rat model with spleen and kidney yang deficiency syndrome and exploration of its biological basis","author":"Han","year":"2019"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"e0225802","DOI":"10.1371\/journal.pone.0225802","article-title":"Influence of Debaryomyces hansenii on bacterial lactase gene diversity in intestinal mucosa of mice with antibiotic-associated diarrhea","volume":"14","author":"He","year":"2019","journal-title":"PLoS One"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"101634","DOI":"10.1016\/j.bpg.2019.101634","article-title":"The Rome IV: irritable bowel syndrome - a functional disorder","author":"Hellstr\u00f6m","year":"2019","journal-title":"Best Pract. Res. Clin. Gastroenterol."},{"key":"ref12","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1016\/j.jcmgh.2015.10.001","article-title":"Enterohemorrhagic Escherichia coli reduce mucus and intermicrovillar bridges in human stem cell-derived colonoids","volume":"2","author":"In","year":"2016","journal-title":"Cell. Mol. Gastroenterol. Hepatol."},{"key":"ref13","doi-asserted-by":"publisher","first-page":"1031844","DOI":"10.1155\/2022\/1031844","article-title":"Correlation between intestinal microflora in irritable bowel syndrome and severity","volume":"2022","author":"Ji","year":"2022","journal-title":"Dis. Markers"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"103","DOI":"10.3870\/1cxh.j.issn.1005-541X.2016.02.12","article-title":"Changes of intestinal microflora in different irritable bowel syndrome subtypes","volume":"28","author":"Ji","year":"2016","journal-title":"J. Clin. Gastroenterol."},{"key":"ref15","doi-asserted-by":"publisher","first-page":"799","DOI":"10.1681\/asn.2019080827","article-title":"Cellular and molecular mechanisms of kidney injury in 2,8-dihydroxyadenine nephropathy","volume":"31","author":"Klinkhammer","year":"2020","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref16","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1186\/s40168-021-01028-7","article-title":"Gut microbiota-derived inosine from dietary barley leaf supplementation attenuates colitis through PPAR\u03b3 signaling activation","volume":"9","author":"Li","year":"2021","journal-title":"Microbiome"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1007\/s13205-020-02558-x","article-title":"Bacterial diversity in intestinal mucosa of mice fed with Dendrobium officinale and high-fat diet. 3","volume":"11","author":"Li","year":"","journal-title":"Biotech"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"3261","DOI":"10.3390\/cells11203261","article-title":"Gut-kidney impairment process of adenine combined with folium sennae-induced diarrhea: association with interactions between lactobacillus intestinalis, bacteroides acidifaciens and acetic acid, inflammation, and kidney function","volume":"11","author":"Li","year":"","journal-title":"Cells"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1007\/s13205-020-02628-0","article-title":"Effect of Gegenqinlian decoction on intestinal mucosal flora in mice with diarrhea induced by high temperature and humidity treatment. 3","volume":"11","author":"Li","year":"","journal-title":"Biotech"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"952647","DOI":"10.3389\/fnut.2022.952647","article-title":"The effect of Qiweibaizhu powder crude polysaccharide on antibiotic-associated diarrhea mice is associated with restoring intestinal mucosal bacteria","volume":"9","author":"Li","year":"2022","journal-title":"Front. Nutr."},{"key":"ref21","doi-asserted-by":"publisher","first-page":"1368","DOI":"10.13288\/j.11-2166\/r.2022.14.012","article-title":"Model building and validation of diarrhea mice with kidney-yang depletion syndrome","volume":"63","author":"Li","year":"","journal-title":"J. Tradit. Chin. Med."},{"key":"ref22","doi-asserted-by":"publisher","first-page":"4","DOI":"10.5152\/tjg.2022.211010","article-title":"Correlation between kidney function and intestinal biological characteristics of adenine and folium sennae induced diarrhea model in mice","volume":"34","author":"Li","year":"2023","journal-title":"Turk J Gastroenterol"},{"key":"ref23","doi-asserted-by":"publisher","first-page":"40","DOI":"10.13422\/j.cnki.syfjx.20231719","article-title":"Sishenwan combined with Tongxie Yaofang treats ulcerative colitis with Spleen-Kidney Yang Deficiency and liver depression","volume":"30","author":"Liu","year":"2024","journal-title":"Chin. J. Exp. Tradit. Med. 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Pract."},{"key":"ref27","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1097\/MOG.0b013e3282f323f3","article-title":"Nutrition and colonic health: the critical role of the microbiota","volume":"24","author":"O'Keefe","year":"2008","journal-title":"Curr. Opin. Gastroenterol."},{"key":"ref28","doi-asserted-by":"publisher","first-page":"1149","DOI":"10.13288\/j.11-2166\/r.2023.11.013","article-title":"Comparative study on five modelling methods of spleen qi deficiency syndrome based on the theory that \u201cdiet and fatigue damage the spleen\u201d","volume":"64","author":"Qiao","year":"2023","journal-title":"J. Tradit. Chin. Med."},{"key":"ref29","doi-asserted-by":"publisher","first-page":"269","DOI":"10.1007\/164_2016_115","article-title":"The role of the gastrointestinal microbiota in visceral pain","volume":"239","author":"Rea","year":"2017","journal-title":"Handb. Exp. Pharmacol."},{"key":"ref30","doi-asserted-by":"publisher","first-page":"219","DOI":"10.13412\/j.cnki.zyyl.2020.04.031","article-title":"The current situation and consideration of animal model evaluation methods in traditional Chinese medicine","volume":"36","author":"Ren","year":"2020","journal-title":"Chin. J. Chin. Mater. Med."},{"key":"ref31","first-page":"117","article-title":"Eference standards for differentiation of traditional Chinese medicine deficiency syndromes","volume":"3","author":"Shen","year":"1983","journal-title":"J. Chin. Integr. Med."},{"key":"ref32","doi-asserted-by":"publisher","first-page":"171","DOI":"10.12938\/bmfh.2024-078","article-title":"The effects of functional biscuits on intestinal mucosal microbiota composition, brain function, and antioxidant activity","volume":"44","author":"Shen","year":"2025","journal-title":"Biosci. Microb. Food Health"},{"key":"ref33","doi-asserted-by":"publisher","first-page":"e28064","DOI":"10.7759\/cureus.28064","article-title":"The role of gut-microbiota in the pathophysiology and therapy of irritable bowel syndrome: a systematic review","volume":"14","author":"Shrestha","year":"2022","journal-title":"Cureus"},{"key":"ref34","doi-asserted-by":"publisher","first-page":"138","DOI":"10.13422\/j.cnki.syfjx.2012.06.003","article-title":"The establish and evaluating of irritable bowel syndrome of hepatic stagnation and spleen deficiency type","volume":"18","author":"Tang","year":"2012","journal-title":"Chin. J. Exp. Tradit. Med. Formulae"},{"key":"ref35","article-title":"Analysis of the gut microbiological characteristics of patients with diarrheal irritable bowel syndrome and its association with somatic and psychiatric symptoms","author":"Tao","year":"2023"},{"key":"ref36","doi-asserted-by":"publisher","first-page":"964847","DOI":"10.3389\/fmicb.2022.964847","article-title":"Sex hormones influence the intestinal microbiota composition in mice","volume":"13","author":"Wu","year":"2022","journal-title":"Front. Microbiol."},{"key":"ref37","doi-asserted-by":"publisher","first-page":"77","DOI":"10.3969\/j.issn.1671-7856.2008.03.019","article-title":"Comparison of modelling methods for adenine and hydrocortisone-induced kidney Yang deficiency model in rats","volume":"28","author":"Xiao","year":"2008","journal-title":"Chin. J. Comp. Med."},{"key":"ref38","doi-asserted-by":"publisher","first-page":"106161","DOI":"10.1016\/j.phrs.2022.106161","article-title":"Pharmacological targeting macrophage phenotype via gut-kidney axis ameliorates renal fibrosis in mice","volume":"178","author":"Xie","year":"2022","journal-title":"Pharmacol. Res."},{"key":"ref39","doi-asserted-by":"publisher","first-page":"1428228","DOI":"10.3389\/fnut.2024.1428228","article-title":"Lipid-lowering and antioxidant effects of Polygonatum fermented liquor: a study on intestinal microbiota and brain-gut axis in mice","volume":"11","author":"Yang","year":"2024","journal-title":"Front. Nutr."},{"key":"ref40","doi-asserted-by":"publisher","first-page":"180","DOI":"10.1007\/s13205-020-02172-x","article-title":"Intestinal microbiota characteristics of mice treated with folium senna decoction gavage combined with restraint and tail pinch stress. 3","volume":"10","author":"Yuan","year":"2020","journal-title":"Biotech"},{"key":"ref41","doi-asserted-by":"publisher","first-page":"626691","DOI":"10.3389\/fmicb.2021.626691","article-title":"Gut microbiota comparison between intestinal contents and mucosa in mice with repeated stress-related diarrhea provides novel insight","volume":"12","author":"Zhang","year":"2021","journal-title":"Front. Microbiol."},{"key":"ref42","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1186\/s12934-024-02307-2","article-title":"Intestinal mucosal microbiota mediate amino acid metabolism involved in the gastrointestinal adaptability to cold and humid environmental stress in mice","volume":"23","author":"Zhang","year":"2024","journal-title":"Microb. Cell Factories"},{"key":"ref43","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1186\/s12866-020-01864-x","article-title":"Role of tryptophan-metabolizing microbiota in mice diarrhea caused by folium sennae extracts","volume":"20","author":"Zhang","year":"2020","journal-title":"BMC Microbiol."},{"key":"ref44","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1007\/s13205-024-03959-y","article-title":"Adenine's impact on mice's gut and kidney varies with the dosage administered and relates to intestinal microorganisms and enzyme activities. 3","volume":"14","author":"Zhou","year":"2024","journal-title":"Biotech"},{"key":"ref45","first-page":"1447","article-title":"Research progress on the regulation of intestinal flora by traditional Chinese medicine in the treatment of irritable bowel syndrome","volume":"40","author":"Zhou","year":"2024","journal-title":"Prac. Tradit. Chin. Med."},{"key":"ref46","doi-asserted-by":"publisher","first-page":"1007609","DOI":"10.3389\/fmicb.2022.1007609","article-title":"Diarrhea with deficiency kidney-yang syndrome caused by adenine combined with folium senna was associated with gut mucosal microbiota","volume":"13","author":"Zhu","year":"2022","journal-title":"Front. 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