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Provincial Department of Education","award":["2024JC-YBQN-0956"],"award-info":[{"award-number":["2024JC-YBQN-0956"]}]},{"name":"Basic Research Project of Shaanxi Provincial Department of Science and Technology","award":["2021ZDLSF03-05"],"award-info":[{"award-number":["2021ZDLSF03-05"]}]},{"name":"Basic Research Project of Shaanxi Provincial Department of Science and Technology","award":["2022-85"],"award-info":[{"award-number":["2022-85"]}]},{"name":"Basic Research Project of Shaanxi Provincial Department of Science and Technology","award":["23JP155"],"award-info":[{"award-number":["23JP155"]}]},{"name":"Basic Research Project of Shaanxi Provincial Department of Science and Technology","award":["2021TD03"],"award-info":[{"award-number":["2021TD03"]}]},{"name":"Basic Research Project of Shaanxi Provincial Department of Science and Technology","award":["2021TD09"],"award-info":[{"award-number":["2021TD09"]}]},{"name":"Basic Research Project of Shaanxi Provincial Department of Science and Technology","award":["2024NLTS128"],"award-info":[{"award-number":["2024NLTS128"]}]},{"name":"Basic Research Project of Shaanxi Provincial Department of Science and Technology","award":["23JC060"],"award-info":[{"award-number":["23JC060"]}]},{"name":"Basic Research Project of Shaanxi Provincial Department of Science and Technology","award":["2024JC-YBQN-0956"],"award-info":[{"award-number":["2024JC-YBQN-0956"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["CIMB"],"abstract":"<jats:p>Background\/Objectives: Gypenosides (Gps) are the main active compounds of Gynostemma and show promise in managing diabetes; nevertheless, the mechanism by which Gps exert anti-diabetic effects is still not fully understood. The aim of this study is to clarify the molecular mechanisms of Gps in ameliorating glucose dysregulation. Methods: Qualitative and quantitative analyses on the chemical components of Gps were performed, respectively. Type 2 diabetes mellitus mouse models were established, and the mice were subsequently treated with Gps at doses of 200, 100, or 50 mg\/kg for 4 weeks. Biochemical markers were measured. Histopathological assessments of hepatic and colonic tissues were conducted. The compositions of the intestinal microbiota, short-chain fatty acids (SCFAs), and bile acids (BAs) in fecal samples were analyzed. Western blotting was applied to examine the activation of relevant signaling pathways. Results: Gps have potent regulatory effects on metabolic homeostasis by improving glucose and lipid profiles and alleviating hepatic tissue damage. Treatment with Gps significantly reduced serum levels of lipopolysaccharides and key pro-inflammatory cytokines (interleukin-6 and tumor necrosis factor-\u03b1). Moreover, Gps enhanced the integrity of the gut barrier by upregulating the level of tight junction proteins (ZO-1 and occludin). Microbiota profiling revealed that Gps markedly increased microbial diversity and richness, decreased the ratio of Firmicutes\/Bacteroidetes, and elevated Bacteroidia abundance from the phylum to the genus level. Targeted metabolomics further demonstrated that Gps modulated gut microbial metabolites by promoting SCFA production and reshaping BA profiles. Specifically, Gps elevated the primary-to-secondary BA ratio while reducing the 12\u03b1-hydroxylated to non-12\u03b1-hydroxylated BA ratio. Mechanistically, Western blotting demonstrated that Gps triggered the hepatic PI3K\/AKT pathway and the intestinal BA\/FXR\/FGF15 axis, suggesting the coordinated regulation of metabolic and gut\u2013liver axis signaling pathways. Conclusions: Gps significantly ameliorate hyperglycemia and hyperlipidemia through a multifaceted mechanism involving gut microbiota modulation, the restoration of intestinal barrier function, and the regulation of microbial metabolites such as SCFAs and BAs. These findings offer novel insights into their mechanism of action via the gut\u2013liver axis.<\/jats:p>","DOI":"10.3390\/cimb47070515","type":"journal-article","created":{"date-parts":[[2025,7,3]],"date-time":"2025-07-03T09:57:39Z","timestamp":1751536659000},"page":"515","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Gypenosides Alleviate Hyperglycemia by Regulating Gut Microbiota Metabolites and Intestinal Permeability"],"prefix":"10.3390","volume":"47","author":[{"given":"Rong","family":"Wang","sequence":"first","affiliation":[{"name":"Xi\u2019an Key Laboratory for Research and Development of Innovative Multi-Target Anti-Hypertensive Drugs, Xi\u2019an Medical University, Xi\u2019an 710021, China"},{"name":"Xi\u2019an Innovative Anti-Hypertensive Drugs International Science and Technology Cooperation Base, Xi\u2019an Medical University, Xi\u2019an 710021, China"},{"name":"Institute of Drug Research, Xi\u2019an Medical University, Xi\u2019an 710021, China"},{"name":"College of Pharmacy, Xi\u2019an Medical University, Xi\u2019an 710021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xue-Feng","family":"Liu","sequence":"additional","affiliation":[{"name":"Shaanxi Institute of Food and Drug Control, Xi\u2019an 710021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kuan","family":"Yang","sequence":"additional","affiliation":[{"name":"Xi\u2019an Key Laboratory for Research and Development of Innovative Multi-Target Anti-Hypertensive Drugs, Xi\u2019an Medical University, Xi\u2019an 710021, China"},{"name":"Xi\u2019an Innovative Anti-Hypertensive Drugs International Science and Technology Cooperation Base, Xi\u2019an Medical University, Xi\u2019an 710021, China"},{"name":"Institute of Drug Research, Xi\u2019an Medical University, Xi\u2019an 710021, China"},{"name":"College of Pharmacy, Xi\u2019an Medical University, Xi\u2019an 710021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li-Li","family":"Yu","sequence":"additional","affiliation":[{"name":"Xi\u2019an Key Laboratory for Research and Development of Innovative Multi-Target Anti-Hypertensive Drugs, Xi\u2019an Medical University, Xi\u2019an 710021, China"},{"name":"Xi\u2019an Innovative Anti-Hypertensive Drugs International Science and Technology Cooperation Base, Xi\u2019an Medical University, Xi\u2019an 710021, China"},{"name":"Institute of Drug Research, Xi\u2019an Medical University, Xi\u2019an 710021, China"},{"name":"College of Pharmacy, Xi\u2019an Medical University, Xi\u2019an 710021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shao-Jing","family":"Liu","sequence":"additional","affiliation":[{"name":"Xi\u2019an Key Laboratory for Research and Development of Innovative Multi-Target Anti-Hypertensive Drugs, Xi\u2019an Medical University, Xi\u2019an 710021, China"},{"name":"Xi\u2019an Innovative Anti-Hypertensive Drugs International Science and Technology Cooperation Base, Xi\u2019an Medical University, Xi\u2019an 710021, China"},{"name":"Institute of Drug Research, Xi\u2019an Medical University, Xi\u2019an 710021, China"},{"name":"College of Pharmacy, Xi\u2019an Medical University, Xi\u2019an 710021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Na-Na","family":"Wang","sequence":"additional","affiliation":[{"name":"Xi\u2019an Key Laboratory for Research and Development of Innovative Multi-Target Anti-Hypertensive Drugs, Xi\u2019an Medical University, Xi\u2019an 710021, China"},{"name":"Xi\u2019an Innovative Anti-Hypertensive Drugs International Science and Technology Cooperation Base, Xi\u2019an Medical University, Xi\u2019an 710021, China"},{"name":"Institute of Drug Research, Xi\u2019an Medical University, Xi\u2019an 710021, China"},{"name":"College of Pharmacy, Xi\u2019an Medical University, Xi\u2019an 710021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun-Mei","family":"Chen","sequence":"additional","affiliation":[{"name":"Xi\u2019an Key Laboratory for Research and Development of Innovative Multi-Target Anti-Hypertensive Drugs, Xi\u2019an Medical University, Xi\u2019an 710021, China"},{"name":"Xi\u2019an Innovative Anti-Hypertensive Drugs International Science and Technology Cooperation Base, Xi\u2019an Medical University, Xi\u2019an 710021, China"},{"name":"Institute of Drug Research, Xi\u2019an Medical University, Xi\u2019an 710021, China"},{"name":"College of Pharmacy, Xi\u2019an Medical University, Xi\u2019an 710021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ya-Qi","family":"Hu","sequence":"additional","affiliation":[{"name":"Xi\u2019an Key Laboratory for Research and Development of Innovative Multi-Target Anti-Hypertensive Drugs, Xi\u2019an Medical University, Xi\u2019an 710021, China"},{"name":"Xi\u2019an Innovative 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China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"109802","DOI":"10.1016\/j.foodres.2020.109802","article-title":"Effect of antioxidant-rich propolis and bee pollen extracts against d-glucose induced type 2 diabetes in rats","volume":"138 Pt B","author":"Laaroussi","year":"2020","journal-title":"Food Res. Int."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Chai, Y., Luo, J., and Bao, Y. (2021). Effects of polygonatum sibiricum saponin on hyperglycemia, gut microbiota composition and metabolic profiles in type 2 diabetes mice. Biomed. Pharmacother., 143.","DOI":"10.1016\/j.biopha.2021.112155"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1186\/s12933-016-0350-4","article-title":"Risks of cardiovascular diseases associated with dipeptidyl peptidase-4 inhibitors and other antidiabetic drugs in patients with type 2 diabetes: A nation-wide longitudinal study","volume":"15","author":"Ou","year":"2016","journal-title":"Cardiovasc. Diabetol."},{"key":"ref_4","first-page":"521","article-title":"Gastrointestinal adverse effects of old and new antidiabetics: How do we deal with them in real life?","volume":"89","year":"2024","journal-title":"Rev. Gastroenterol. Mex."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Zolkepli, H., Widodo, R.-T., Mahmood, S., Salim, N., Awang, K., Ahmad, N., and Othman, R. (2022). A review on the delivery of plant-based antidiabetic agents using nanocarriers: Current status and their role in combatting hyperglycaemia. Polymers, 14.","DOI":"10.3390\/polym14152991"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.carbpol.2014.12.032","article-title":"Purification, characterization and neuroprotective effects of a polysaccharide from gynostemma pentaphyllum","volume":"122","author":"Jia","year":"2015","journal-title":"Carbohydr. Polym."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"4339","DOI":"10.1039\/D0FO00395F","article-title":"Jiaogulan tea (gpostemma pentaphyllum) potentiates the antidiabetic effect of white tea via the ampk and pi3k pathways in c57bl\/6 mice","volume":"11","author":"Xia","year":"2020","journal-title":"Food Funct."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"8000","DOI":"10.1002\/fsn3.4250","article-title":"The potential of gynostemma pentaphyllum in the treatment of hyperlipidemia and its interaction with the lox1-pi3k-akt-enos pathway","volume":"12","author":"Shen","year":"2024","journal-title":"Food Sci. Nutr."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1016\/j.oraloncology.2008.05.012","article-title":"Gypenosides induced g0\/g1 arrest via chk2 and apoptosis through endoplasmic reticulum stress and mitochondria-dependent pathways in human tongue cancer scc-4 cells","volume":"45","author":"Chen","year":"2009","journal-title":"Oral Oncol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1089\/jmf.2007.0148","article-title":"Potential hypoglycemic effect of an ethanol extract of gynostemma pentaphyllum in c57bl\/ksj-db\/db mice","volume":"11","author":"Yeo","year":"2008","journal-title":"J. Med. Food"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"361","DOI":"10.4103\/1673-5374.265557","article-title":"Ethanol extract from gynostemma pentaphyllum ameliorates dopaminergic neuronal cell death in transgenic mice expressing mutant a53t human alpha-synuclein","volume":"15","author":"Park","year":"2020","journal-title":"Neural Regen. Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"37182","DOI":"10.7554\/eLife.37182","article-title":"A selective gut bacterial bile salt hydrolase alters host metabolism","volume":"7","author":"Yao","year":"2018","journal-title":"Elife"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1007\/s12272-014-0441-2","article-title":"Hypoglycemic effect of gynostemma pentaphyllum saponins by enhancing the nrf2 signaling pathway in stz-inducing diabetic rats","volume":"39","author":"Gao","year":"2016","journal-title":"Arch. Pharm. Res."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Xie, J.-B., Xie, P., Guo, M., Li, F.-F., Xiao, M.-Y., Qi, Y.-S., Pei, W.-J., Luo, H.-T., Gu, Y.-L., and Piao, X.-L. (2023). Protective effect of heat-processed gynostemma pentaphyllum on high fat diet-induced glucose metabolic disorders mice. Front. Pharmacol., 14.","DOI":"10.3389\/fphar.2023.1215150"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Iatcu, O.-C., Hamamah, S., and Covasa, M. (2024). Harnessing prebiotics to improve type 2 diabetes outcomes. Nutrients, 16.","DOI":"10.3390\/nu16203447"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Koliada, A., Syzenko, G., Moseiko, V., Budovska, L., Puchkov, K., Perederiy, V., Gavalko, Y., Dorofeyev, A., Romanenko, M., and Tkach, S. (2017). Association between body mass index and firmicutes\/bacteroidetes ratio in an adult ukrainian population. BMC Microbiol., 17.","DOI":"10.1186\/s12866-017-1027-1"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2325","DOI":"10.1194\/jlr.R036012","article-title":"The role of short-chain fatty acids in the interplay between diet, gut microbiota, and host energy metabolism","volume":"54","author":"Groen","year":"2013","journal-title":"J. Lipid Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1530\/JME-19-0132","article-title":"Butyrate modulates diabetes-linked gut dysbiosis: Epigenetic and mechanistic modifications","volume":"64","author":"Noureldein","year":"2020","journal-title":"J. Mol. Endocrinol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"17480","DOI":"10.18632\/aging.103756","article-title":"Fecal microbiota transplantation alters the susceptibility of obese rats to type 2 diabetes mellitus","volume":"12","author":"Zhang","year":"2020","journal-title":"Aging"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"e35421","DOI":"10.1016\/j.heliyon.2024.e35421","article-title":"The mechanism of bile acid metabolism regulating lipid metabolism and inflammatory response in t2dm through the gut-liver axis","volume":"10","author":"Wang","year":"2024","journal-title":"Heliyon"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Gao, R., Meng, X., Xue, Y., Mao, M., Liu, Y., Tian, X., Sui, B., Li, X., and Zhang, P. (2022). Bile acids-gut microbiota crosstalk contributes to the improvement of type 2 diabetes mellitus. Front. Pharmacol., 13.","DOI":"10.3389\/fphar.2022.1027212"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Jiang, F.-Y., Yue, S.-R., Tan, Y.-Y., Tang, N., Xu, Y.-S., Zhang, B.-J., Mao, Y.-J., Xue, Z.-S., Lu, A.-P., and Liu, B.-C. (2024). Gynostemma pentaphyllum extract alleviates NASH in mice: Exploration of inflammation and gut microbiota. Nutrients, 16.","DOI":"10.3390\/nu16111782"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"110717","DOI":"10.1016\/j.foodres.2021.110717","article-title":"Coix seed polysaccharides alleviate type 2 diabetes mellitus via gut microbiota-derived short-chain fatty acids activation of igf1\/pi3k\/akt signaling","volume":"150 Pt A","author":"Xia","year":"2021","journal-title":"Food Res. Int."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Cheng, N., Chen, S., Liu, X., Zhao, H., and Cao, W. (2019). Impact of schisandrachinensis bee pollen on nonalcoholic fatty liver disease and gut microbiota in high fat diet induced obese mice. Nutrients, 11.","DOI":"10.3390\/nu11020346"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1016\/j.chroma.2014.10.064","article-title":"A liquid chromatography-tandem mass spectrometry-based method for the simultaneous determination of hydroxy sterols and bile acids","volume":"1371","author":"John","year":"2014","journal-title":"J. Chromatogr. A"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1860","DOI":"10.1111\/1751-7915.13629","article-title":"Protective effect of lactobacillus salivarius li01 on thioacetamide-induced acute liver injury and hyperammonaemia","volume":"13","author":"Yang","year":"2020","journal-title":"Microb. Biotechnol."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Wu, D., Ding, L., Tang, X., Wang, W., Chen, Y., and Zhang, T. (2019). Baicalin protects against hypertension-associated intestinal barrier impairment in part through enhanced microbial production of short-chain fatty acids. Front. Pharmacol., 10.","DOI":"10.3389\/fphar.2019.01271"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1186\/s10020-021-00414-z","article-title":"The effect and mechanism of jiao-tai-wan in the treatment of diabetes mellitus with depression based on network pharmacology and experimental analysis","volume":"27","author":"Tang","year":"2021","journal-title":"Mol. Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"3390","DOI":"10.7150\/ijbs.69833","article-title":"Dynamics of the gut-liver axis in rats with varying fibrosis severity","volume":"18","author":"Xiang","year":"2022","journal-title":"Int. J. Biol. Sci."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Li, G., Lu, P.-X., Liang, H.-Z., Zheng, W., Chen, X.-J., Zhang, J., Song, J., Yang, G., Wang, Y.-X., and Zhang, T. (2023). An effective and high-throughput sample preparation method involving demalonylation followed by an ultrahigh-performance liquid chromatography-charged aerosol detector for analyzing gypenoside xlix and gypenoside a in gynostemma longipes. J. Pharm. Biomed. Anal., 230.","DOI":"10.1016\/j.jpba.2023.115393"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Yao, B., Pan, B., Tian, T., Su, X., Zhang, S., Li, H., Li, W., Wang, Y., Lv, S., and Zhang, Z. (2022). Baihu renshen decoction ameliorates type 2 diabetes mellitus in rats through affecting gut microbiota enhancing gut permeability and inhibiting tlr4\/nf-kappab-mediated inflammatory response. Front. Cell Infect. Microbiol., 12.","DOI":"10.3389\/fcimb.2022.1051962"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1093\/jn\/nxz233","article-title":"Dietary supplementation with galactooligosaccharides attenuates high-fat, high-cholesterol diet-induced glucose intolerance and disruption of colonic mucin layer in c57bl\/6 mice and reduces atherosclerosis in ldlr-\/- mice","volume":"150","author":"Ghosh","year":"2020","journal-title":"J. Nutr."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"118957","DOI":"10.1016\/j.jep.2024.118957","article-title":"The total alkaloids of berberidis cortex alleviate type 2 diabetes mellitus by regulating gut microbiota, inflammation and liver gluconeogenesis","volume":"337","author":"Tao","year":"2025","journal-title":"J. Ethnopharmacol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"107483","DOI":"10.1016\/j.phrs.2024.107483","article-title":"Targeting gut microbiota as a therapeutic target in T2DM: A review of multi-target interactions of probiotics, prebiotics, postbiotics, and synbiotics with the intestinal barrier","volume":"210","author":"Chen","year":"2024","journal-title":"Pharmacol. Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"117815","DOI":"10.1016\/j.jep.2024.117815","article-title":"In-depth investigation of the therapeutic effect of tribulus terrestris l. On type 2 diabetes based on intestinal microbiota and feces metabolomics","volume":"325","author":"Meng","year":"2024","journal-title":"J. Ethnopharmacol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"115706","DOI":"10.1016\/j.foodres.2025.115706","article-title":"Chayote pectin regulates blood glucose through the gut-liver axis: Gut microbes\/scfas\/foxo1 signaling pathways","volume":"202","author":"Guo","year":"2025","journal-title":"Food Res. Int."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"964","DOI":"10.1161\/CIRCULATIONAHA.116.024545","article-title":"High-fiber diet and acetate supplementation change the gut microbiota and prevent the development of hypertension and heart failure in hypertensive mice","volume":"135","author":"Marques","year":"2017","journal-title":"Circulation"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Lu, K., Shan, S., Zeng, Y., and Yang, G. (2025). Neohesperidin mitigates high-fat-diet-induced colitis in vivo by modulating gut microbiota and enhancing scfas synthesis. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26020534"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"8797","DOI":"10.1021\/acs.jafc.1c02925","article-title":"Lactobacillus rhamnosus lra05 ameliorate hyperglycemia through a regulating glucagon-mediated signaling pathway and gut microbiota in type 2 diabetic mice","volume":"69","author":"Wu","year":"2021","journal-title":"J. Agric. Food Chem."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Wang, Y., Yu, J., Chen, B., Jin, W., Wang, M., Chen, X., Jian, M., Sun, L., and Piao, C. (2024). Bile acids as a key target: Traditional chinese medicine for precision management of insulin resistance in type 2 diabetes mellitus through the gut microbiota-bile acids axis. Front. Endocrinol., 15.","DOI":"10.3389\/fendo.2024.1481270"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Dong, H., Liu, X., Song, G., Peng, W., Sun, X., Fang, W., and Qi, W. (2025). Imbalance of bile acids metabolism mediated by gut microbiota contributed to metabolic disorders in diabetic model mice. Biology, 14.","DOI":"10.3390\/biology14030291"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Wei, M., Huang, F., Zhao, L., Zhang, Y., Yang, W., Wang, S., Li, M., Han, X., Ge, K., and Qu, C. (2020). A dysregulated bile acid-gut microbiota axis contributes to obesity susceptibility. Ebiomedicine, 55.","DOI":"10.1016\/j.ebiom.2020.102766"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1002\/hep.30612","article-title":"Bile acid homeostasis in a cholesterol 7alpha-hydroxylase and sterol 27-hydroxylase double knockout mouse model","volume":"70","author":"Rizzolo","year":"2019","journal-title":"Hepatology"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"154264","DOI":"10.1016\/j.phymed.2022.154264","article-title":"Simiao wan modulates the gut microbiota and bile acid metabolism during improving type 2 diabetes mellitus in mice","volume":"104","author":"Chen","year":"2022","journal-title":"Phytomedicine"}],"container-title":["Current Issues in Molecular Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1467-3045\/47\/7\/515\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:04:06Z","timestamp":1760033046000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1467-3045\/47\/7\/515"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,3]]},"references-count":44,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2025,7]]}},"alternative-id":["cimb47070515"],"URL":"https:\/\/doi.org\/10.3390\/cimb47070515","relation":{},"ISSN":["1467-3045"],"issn-type":[{"value":"1467-3045","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,3]]}}}