{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T01:42:29Z","timestamp":1792806149006,"version":"4.5.0"},"reference-count":57,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2024,7,20]],"date-time":"2024-07-20T00:00:00Z","timestamp":1721433600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the National Natural Science Foundation of China","award":["82274174"],"award-info":[{"award-number":["82274174"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"crossref"}]},{"name":"the National Natural Science Foundation of China","award":["2022-I2M-1-018"],"award-info":[{"award-number":["2022-I2M-1-018"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"crossref"}]},{"name":"the CAMS Innovation Fund for Medical Sciences (CIFMS)","award":["82274174"],"award-info":[{"award-number":["82274174"]}]},{"name":"the CAMS Innovation Fund for Medical Sciences (CIFMS)","award":["2022-I2M-1-018"],"award-info":[{"award-number":["2022-I2M-1-018"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Diabetic nephropathy (DN), one of the leading causes of end-stage kidney failure worldwide, is closely associated with high mortality in diabetic patients. However, therapeutic drugs for DN are still lacking. Ramulus Mori alkaloids (SZ-A), an effective component of alkaloids extracted from Ramulus Mori, have been found to improve glucose and lipid metabolism to mitigate diabetes and obesity; however, few studies have focused on their effects on DN progression. Thus, we investigated the protective role of SZ-A on DN through 16S rRNA sequencing, non-targeted metabolomics, and fecal microbiota transplantation (FMT) experiments. To address our hypothesis, we established the DN mouse model by combining a high-fat diet (HFD) with streptozotocin (STZ) injection. Herein, we demonstrated that SZ-A supplementation was recalcitrant to renal injury in DN mice, improving glomerular morphology, reversing the blood biochemistry parameters, and ameliorating podocyte injury. Importantly, the composition of the gut microbiota altered after SZ-A treatment, especially with the elevated abundance of Dubosiella and the increased level of serum pentadecanoic acid. FMT experiments further revealed that the gut microbiota exerted critical effects in mediating the beneficial roles of SZ-A. In vitro experiments proved that pentadecanoic acid administration improved podocyte apoptosis induced by AGEs. Taken together, SZ-A play a renoprotective role, possibly through regulating the gut microbiota and promoting pentadecanoic acid production. Our current study lends support to more extensive clinical applications of SZ-A.<\/jats:p>","DOI":"10.3390\/nu16142346","type":"journal-article","created":{"date-parts":[[2024,7,22]],"date-time":"2024-07-22T08:24:59Z","timestamp":1721636699000},"page":"2346","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Ramulus Mori (Sangzhi) Alkaloids Alleviate Diabetic Nephropathy through Improving Gut Microbiota Disorder"],"prefix":"10.3390","volume":"16","author":[{"given":"Wenxiu","family":"Liu","sequence":"first","affiliation":[{"name":"Institute of Medicinal Plant Development, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100193, China"},{"name":"Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Beijing 100193, China"},{"name":"Diabetes Research Center, Chinese Academy of Medical Sciences, Beijing 100193, China"},{"name":"Key Laboratory of Efficacy Evaluation of Chinese Medicine against Glyeolipid Metabolism Disorder Disease, State Administration of Traditional Chinese Medicine, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saijun","family":"Xu","sequence":"additional","affiliation":[{"name":"Institute of Medicinal Plant Development, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5292-7842","authenticated-orcid":false,"given":"Bin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Institute of Medicinal Plant Development, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100193, China"},{"name":"Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Beijing 100193, China"},{"name":"Diabetes Research Center, Chinese Academy of Medical Sciences, Beijing 100193, China"},{"name":"Key Laboratory of Efficacy Evaluation of Chinese Medicine against Glyeolipid Metabolism Disorder Disease, State Administration of Traditional Chinese Medicine, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaobo","family":"Sun","sequence":"additional","affiliation":[{"name":"Institute of Medicinal Plant Development, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100193, China"},{"name":"Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Beijing 100193, China"},{"name":"Diabetes Research Center, Chinese Academy of Medical Sciences, Beijing 100193, China"},{"name":"Key Laboratory of Efficacy Evaluation of Chinese Medicine against Glyeolipid Metabolism Disorder Disease, State Administration of Traditional Chinese Medicine, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,7,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1038\/nrendo.2013.184","article-title":"Diabetic nephropathy: Diagnosis and treatment","volume":"9","author":"Fineberg","year":"2013","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"108357","DOI":"10.1016\/j.jdiacomp.2022.108357","article-title":"Present and future directions in diabetic kidney disease","volume":"36","author":"Limonte","year":"2022","journal-title":"J. Diabetes Complicat."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Chen, D.Q., Wu, J., and Li, P. (2022). Therapeutic mechanism and clinical application of Chinese herbal medicine against diabetic kidney disease. Front. Pharmacol., 13.","DOI":"10.3389\/fphar.2022.1055296"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"112542","DOI":"10.1016\/j.jep.2020.112542","article-title":"Antiobesity effect of ethanolic extract of Ramulus mori in differentiated 3T3-L1 adipocytes and high-fat diet-induced obese mice","volume":"251","author":"Park","year":"2020","journal-title":"J. Ethnopharmacol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"644","DOI":"10.1002\/pca.3117","article-title":"From metabolomic analysis to quality assessment and biosynthetic insight in traditional Chinese medicine: Mulberry tree as a case study","volume":"33","author":"Tian","year":"2022","journal-title":"Phytochem. Anal."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1956","DOI":"10.1007\/s12011-021-02788-x","article-title":"Research on Transfer Rate of Heavy Metals and Harmful Elements in Traditional Chinese Medicine Extraction and Refining Processes and Product Health Risk Assessment","volume":"200","author":"Jin","year":"2022","journal-title":"Biol. Trace Elem. Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"7121356","DOI":"10.1155\/2016\/7121356","article-title":"Randomized, Double-Blinded, Double-Dummy, Active-Controlled, and Multiple-Dose Clinical Study Comparing the Efficacy and Safety of Mulberry Twig (Ramulus Mori, Sangzhi) Alkaloid Tablet and Acarbose in Individuals with Type 2 Diabetes Mellitus","volume":"2016","author":"Li","year":"2016","journal-title":"Evid. Based Complement. Alternat. Med."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Liu, Q., Liu, S., Cao, H., Ji, W., Li, C., Huan, Y., Lei, L., Fu, Y., Gao, X., and Liu, Y. (2021). Ramulus Mori (Sangzhi) Alkaloids (SZ-A) Ameliorate Glucose Metabolism Accompanied by the Modulation of Gut Microbiota and Ileal Inflammatory Damage in Type 2 Diabetic KKAy Mice. Front. Pharmacol., 12.","DOI":"10.3389\/fphar.2021.642400"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Sun, Q.W., Lian, C.F., Chen, Y.M., Ye, J., Chen, W., Gao, Y., Wang, H.L., Gao, L.L., Liu, Y.L., and Yang, Y.F. (2022). Ramulus Mori (Sangzhi) Alkaloids Ameliorate Obesity-Linked Adipose Tissue Metabolism and Inflammation in Mice. Nutrients, 14.","DOI":"10.3390\/nu14235050"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1095","DOI":"10.1136\/gutjnl-2021-324053","article-title":"Host and gut microbial tryptophan metabolism and type 2 diabetes: An integrative analysis of host genetics, diet, gut microbiome and circulating metabolites in cohort studies","volume":"71","author":"Qi","year":"2022","journal-title":"Gut"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"716","DOI":"10.1136\/gutjnl-2020-323617","article-title":"Microbiota engraftment after faecal microbiota transplantation in obese subjects with type 2 diabetes: A 24-week, double-blind, randomised controlled trial","volume":"71","author":"Ng","year":"2022","journal-title":"Gut"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1267","DOI":"10.1681\/ASN.2019101029","article-title":"Dietary Fiber Protects against Diabetic Nephropathy through Short-Chain Fatty Acid-Mediated Activation of G Protein-Coupled Receptors GPR43 and GPR109A","volume":"31","author":"Li","year":"2020","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.nutres.2022.10.003","article-title":"Lactobacillus-fermented yogurt exerts hypoglycemic, hypocholesterolemic, and anti-inflammatory activities in STZ-induced diabetic Wistar rats","volume":"108","author":"Ezzat","year":"2022","journal-title":"Nutr. Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2803","DOI":"10.7150\/thno.40571","article-title":"Dysbiosis of intestinal microbiota mediates tubulointerstitial injury in diabetic nephropathy via the disruption of cholesterol homeostasis","volume":"10","author":"Hu","year":"2020","journal-title":"Theranostics"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1835","DOI":"10.1038\/s41467-019-09735-4","article-title":"Gut microbiome-derived phenyl sulfate contributes to albuminuria in diabetic kidney disease","volume":"10","author":"Kikuchi","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Liu, D., Ye, J., Yan, Y., Chen, Y., Wang, H., Wang, M., Feng, Y., Li, R., Xu, X., and Jiang, Y. (2023). Ramulus mori (Sangzhi) alkaloids regulates gut microbiota disorder and its metabolism profiles in obese mice induced by a high-fat diet. Front. Pharmacol., 14.","DOI":"10.3389\/fphar.2023.1166635"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1021\/ac051312t","article-title":"Solvent-dependent metabolite distribution, clustering, and protein extraction for serum profiling with mass spectrometry","volume":"78","author":"Want","year":"2006","journal-title":"Anal. Chem."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1016\/j.aca.2013.01.015","article-title":"UPLC-ESI-QTOF\/MS and multivariate data analysis for blood plasma and serum metabolomics: Effect of experimental artefacts and anticoagulant","volume":"768","author":"Barri","year":"2013","journal-title":"Anal. Chim. Acta"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"106367","DOI":"10.1016\/j.phrs.2022.106367","article-title":"Inulin-type fructans change the gut microbiota and prevent the development of diabetic nephropathy","volume":"183","author":"Luo","year":"2022","journal-title":"Pharmacol. Res."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Pi, Y., Wu, Y., Zhang, X., Lu, D., Han, D., Zhao, J., Zheng, X., Zhang, S., Ye, H., and Lian, S. (2023). Gut microbiota-derived ursodeoxycholic acid alleviates low birth weight-induced colonic inflammation by enhancing M2 macrophage polarization. Microbiome, 11.","DOI":"10.1186\/s40168-022-01458-x"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1038\/s41572-020-0196-7","article-title":"Podocytopathies","volume":"6","author":"Kopp","year":"2020","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"850","DOI":"10.1016\/j.kint.2019.05.015","article-title":"From podocyte biology to novel cures for glomerular disease","volume":"96","author":"Torban","year":"2019","journal-title":"Kidney Int."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"106710","DOI":"10.1016\/j.phrs.2023.106710","article-title":"Broadening horizons in mechanisms, management, and treatment of diabetic kidney disease","volume":"190","author":"Petrazzuolo","year":"2023","journal-title":"Pharmacol. Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1016\/j.kint.2022.05.012","article-title":"Molecular mechanisms and therapeutic targets for diabetic kidney disease","volume":"102","author":"Tuttle","year":"2022","journal-title":"Kidney Int."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1194\/jlr.P040501","article-title":"Altered renal lipid metabolism and renal lipid accumulation in human diabetic nephropathy","volume":"55","author":"Scherzer","year":"2014","journal-title":"J. Lipid Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1038\/s41581-021-00393-8","article-title":"Pathophysiology of diabetic kidney disease: Impact of SGLT2 inhibitors","volume":"17","author":"DeFronzo","year":"2021","journal-title":"Nat. Rev. Nephrol."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Chen, Y.M., Lian, C.F., Sun, Q.W., Wang, T.T., Liu, Y.Y., Ye, J., Gao, L.L., Yang, Y.F., Liu, S.N., and Shen, Z.F. (2022). Ramulus Mori (Sangzhi) Alkaloids Alleviate High-Fat Diet-Induced Obesity and Nonalcoholic Fatty Liver Disease in Mice. Antioxidants, 11.","DOI":"10.3390\/antiox11050905"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Lei, L., Huan, Y., Liu, Q., Li, C., Cao, H., Ji, W., Gao, X., Fu, Y., Li, P., and Zhang, R. (2022). Morus alba L. (Sangzhi) Alkaloids Promote Insulin Secretion, Restore Diabetic \u03b2-Cell Function by Preventing Dedifferentiation and Apoptosis. Front. Pharmacol., 13.","DOI":"10.3389\/fphar.2022.841981"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Meng, Z., Xu, C., Liu, H., Gao, X., Li, X., Lin, W., Ma, X., Yang, C., Hao, M., and Zhao, K. (2023). Effects of mulberry twig alkaloids(Sangzhi alkaloids) and metformin on blood glucose fluctuations in combination with premixed insulin-treated patients with type 2 diabetes. Front. Endocrinol., 14.","DOI":"10.3389\/fendo.2023.1272112"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"108314","DOI":"10.1016\/j.pharmthera.2022.108314","article-title":"A natural products solution to diabetic nephropathy therapy","volume":"241","author":"Hu","year":"2023","journal-title":"Pharmacol. Ther."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2749","DOI":"10.1016\/j.apsb.2020.12.020","article-title":"Clinical efficacies, underlying mechanisms and molecular targets of Chinese medicines for diabetic nephropathy treatment and management","volume":"11","author":"Tang","year":"2021","journal-title":"Acta Pharm. Sin. B."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"153663","DOI":"10.1016\/j.phymed.2021.153663","article-title":"Tinospora cordifolia activates PPAR\u03b3 pathway and mitigates glomerular and tubular cell injury in diabetic kidney disease","volume":"91","author":"Patial","year":"2021","journal-title":"Phytomedicine"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1016\/j.mcna.2023.03.004","article-title":"Diabetic Kidney Disease: An Update","volume":"107","author":"Gupta","year":"2023","journal-title":"Med. Clin. N. Am."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2455","DOI":"10.1038\/s41401-023-01140-4","article-title":"Satellite cell-derived exosome-mediated delivery of microRNA-23a\/27a\/26a cluster ameliorates the renal tubulointerstitial fibrosis in mouse diabetic nephropathy","volume":"44","author":"Ji","year":"2023","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Li, C., Liu, Q., Ji, W., Fu, Y., Cao, H., Huan, Y., Lei, L., Gao, X., Chen, L., and Feng, C. (2023). New anti-diabetic drug Morus alba L. (Sangzhi) alkaloids (SZ-A) improves diabetic nephropathy through ameliorating inflammation and fibrosis in diabetic rats. Front. Med., 10.","DOI":"10.3389\/fmed.2023.1164242"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1038\/s41581-022-00647-z","article-title":"Gut microbiome studies in CKD: Opportunities, pitfalls and therapeutic potential","volume":"19","author":"Krukowski","year":"2023","journal-title":"Nat. Rev. Nephrol."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Gurung, M., Li, Z., You, H., Rodrigues, R., Jump, D.B., Morgun, A., and Shulzhenko, N. (2020). Role of gut microbiota in type 2 diabetes pathophysiology. EBioMedicine, 51.","DOI":"10.1016\/j.ebiom.2019.11.051"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1038\/s41581-018-0018-2","article-title":"The gut microbiota and the brain-gut-kidney axis in hypertension and chronic kidney disease","volume":"14","author":"Yang","year":"2018","journal-title":"Nat. Rev. Nephrol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1332","DOI":"10.1016\/j.cell.2016.05.041","article-title":"From Dietary Fiber to Host Physiology: Short-Chain Fatty Acids as Key Bacterial Metabolites","volume":"165","author":"Koh","year":"2016","journal-title":"Cell"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1078\/0944-7113-00065","article-title":"Alpha-glucosidase inhibition from a Chinese medical herb (Ramulus mori) in normal and diabetic rats and mice","volume":"9","author":"Ye","year":"2002","journal-title":"Phytomedicine"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Yang, S., Mi, J., Liu, Z., Wang, B., Xia, X., Wang, R., Liu, Y., and Li, Y. (2017). Pharmacokinetics, Tissue Distribution, and Elimination of Three Active Alkaloids in Rats after Oral Administration of the Effective Fraction of Alkaloids from Ramulus Mori, an Innovative Hypoglycemic Agent. Molecules, 22.","DOI":"10.3390\/molecules22101616"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1491","DOI":"10.1210\/jc.2017-02114","article-title":"Connection Between BMI-Related Plasma Metabolite Profile and Gut Microbiota","volume":"103","author":"Ottosson","year":"2018","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Li, Y., Su, X., Gao, Y., Lv, C., Gao, Z., Liu, Y., Wang, Y., Li, S., and Wang, Z. (2020). The potential role of the gut microbiota in modulating renal function in experimental diabetic nephropathy murine models established in same environment. Biochim. Biophys. Acta Mol. Basis Dis., 1866.","DOI":"10.1016\/j.bbadis.2020.165764"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1038\/s41387-019-0097-6","article-title":"The flavonoid-rich Quzhou Fructus Aurantii extract modulates gut microbiota and prevents obesity in high-fat diet-fed mice","volume":"9","author":"Bai","year":"2019","journal-title":"Nutr. Diabetes"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"e1800298","DOI":"10.1002\/mnfr.201800298","article-title":"The Probiotic Lactobacillus fermentum Prevents Dysbiosis and Vascular Oxidative Stress in Rats with Hypertension Induced by Chronic Nitric Oxide Blockade","volume":"62","author":"Toral","year":"2018","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1016\/j.ijbiomac.2022.03.077","article-title":"Moutan Cortex polysaccharide ameliorates diabetic kidney disease via modulating gut microbiota dynamically in rats","volume":"206","author":"Zhang","year":"2022","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1038\/s41467-020-20313-x","article-title":"Transkingdom interactions between Lactobacilli and hepatic mitochondria attenuate western diet-induced diabetes","volume":"12","author":"Rodrigues","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/j.ijbiomac.2022.05.109","article-title":"Hypoglycaemic and anti-ageing activities of green alga Ulva lactuca polysaccharide via gut microbiota in ageing-associated diabetic mice","volume":"212","author":"Chen","year":"2022","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"167043","DOI":"10.1016\/j.scitotenv.2023.167043","article-title":"Iron overload induces colitis by modulating ferroptosis and interfering gut microbiota in mice","volume":"905","author":"Gu","year":"2023","journal-title":"Sci. Total Environ."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"e8893","DOI":"10.7717\/peerj.8893","article-title":"Synthetic dietary inulin, Fuji FF, delays development of diet-induced obesity by improving gut microbiota profiles and increasing short-chain fatty acid production","volume":"8","author":"Igarashi","year":"2020","journal-title":"PeerJ"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Zhao, T., Zhang, H., Yin, X., Zhao, H., Ma, L., Yan, M., Peng, L., Wang, Q., Dong, X., and Li, P. (2020). Tangshen formula modulates gut Microbiota and reduces gut-derived toxins in diabetic nephropathy rats. Biomed. Pharmacother., 129.","DOI":"10.1016\/j.biopha.2020.110325"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1038\/s41366-020-00712-2","article-title":"Identification of gut microbiota and microbial metabolites regulated by an antimicrobial peptide lipocalin 2 in high fat diet-induced obesity","volume":"45","author":"Qiu","year":"2021","journal-title":"Int. J. Obes."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"E742","DOI":"10.1152\/ajpendo.00523.2019","article-title":"Supplementation of a propionate-producing consortium improves markers of insulin resistance in an in vitro model of gut-liver axis","volume":"318","year":"2020","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"116780","DOI":"10.1016\/j.carbpol.2020.116780","article-title":"Roles of gut microbiota and metabolites in a homogalacturonan-type pectic polysaccharide from Ficus pumila Linn. fruits mediated amelioration of obesity","volume":"248","author":"Wu","year":"2020","journal-title":"Carbohydr. Polym."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1534","DOI":"10.1038\/s41564-023-01418-7","article-title":"Parabacteroides distasonis uses dietary inulin to suppress NASH via its metabolite pentadecanoic acid","volume":"8","author":"Wei","year":"2023","journal-title":"Nat. Microbiol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"118008","DOI":"10.1016\/j.jep.2024.118008","article-title":"Identification of anti-fibrotic and pro-apoptotic bioactive compounds from Ganoderma formosanum and their possible mechanisms in modulating TGF-\u03b21-induced lung fibrosis","volume":"327","author":"Cheng","year":"2024","journal-title":"J. Ethnopharmacol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1518","DOI":"10.1002\/med.21883","article-title":"Metabolomics as a tool for the early diagnosis and prognosis of diabetic kidney disease","volume":"42","author":"Pereira","year":"2022","journal-title":"Med. Res. Rev."}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/16\/14\/2346\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:20:09Z","timestamp":1760109609000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/16\/14\/2346"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,7,20]]},"references-count":57,"journal-issue":{"issue":"14","published-online":{"date-parts":[[2024,7]]}},"alternative-id":["nu16142346"],"URL":"https:\/\/doi.org\/10.3390\/nu16142346","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,7,20]]}}}