{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T15:02:23Z","timestamp":1791385343031,"version":"4.3.3"},"reference-count":100,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2024,4,14]],"date-time":"2024-04-14T00:00:00Z","timestamp":1713052800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81973022"],"award-info":[{"award-number":["81973022"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["TY202101003"],"award-info":[{"award-number":["TY202101003"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"BYHEALTH Nutrition and Health Research Foundation","award":["81973022"],"award-info":[{"award-number":["81973022"]}]},{"name":"BYHEALTH Nutrition and Health Research Foundation","award":["TY202101003"],"award-info":[{"award-number":["TY202101003"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Silymarin, salvianolic acids B, and puerarin were considered healthy food agents with tremendous potential to ameliorate non-alcoholic fatty liver disease (NAFLD). However, the mechanisms by which they interact with gut microbiota to exert benefits are largely unknown. After 8 weeks of NAFLD modeling, C57BL\/6J mice were randomly divided into five groups and fed a normal diet, high-fat diet (HFD), or HFD supplemented with a medium or high dose of Silybum marianum extract contained silymarin or polyherbal extract contained silymarin, salvianolic acids B, and puerarin for 16 weeks, respectively. The untargeted metabolomics and 16S rRNA sequencing were used for molecular mechanisms exploration. The intervention of silymarin and polyherbal extract significantly improved liver steatosis and recovered liver function in the mice, accompanied by an increase in probiotics like Akkermansia and Blautia, and suppressed Clostridium, which related to changes in the bile acids profile in feces and serum. Fecal microbiome transplantation confirmed that this alteration of microbiota and its metabolites were responsible for the improvement in NAFLD. The present study substantiated that alterations of the gut microbiota upon silymarin and polyherbal extract intervention have beneficial effects on HFD-induced hepatic steatosis and suggested the pivotal role of gut microbiota and its metabolites in the amelioration of NAFLD.<\/jats:p>","DOI":"10.3390\/nu16081169","type":"journal-article","created":{"date-parts":[[2024,4,15]],"date-time":"2024-04-15T03:56:13Z","timestamp":1713153373000},"page":"1169","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Supplementation of Silymarin Alone or in Combination with Salvianolic Acids B and Puerarin Regulates Gut Microbiota and Its Metabolism to Improve High-Fat Diet-Induced NAFLD in Mice"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-0580-3757","authenticated-orcid":false,"given":"Xin","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Nutrition, School of Public Health, Sun Yat-sen University (Northern Campus), Guangzhou 510080, China"},{"name":"Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Guangzhou 510080, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yufeng","family":"Jin","sequence":"additional","affiliation":[{"name":"Department of Nutrition, School of Public Health, Sun Yat-sen University (Northern Campus), Guangzhou 510080, China"},{"name":"Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Guangzhou 510080, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Can","family":"Di","sequence":"additional","affiliation":[{"name":"BYHEALTH Institute of Nutrition and Health, Guangzhou 510663, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yupeng","family":"Zeng","sequence":"additional","affiliation":[{"name":"Department of Nutrition, School of Public Health, Sun Yat-sen University (Northern Campus), Guangzhou 510080, China"},{"name":"Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Guangzhou 510080, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuqing","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Nutrition, School of Public Health, Sun Yat-sen University (Northern Campus), Guangzhou 510080, China"},{"name":"Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Guangzhou 510080, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Nutrition, School of Public Health, Sun Yat-sen University (Northern Campus), Guangzhou 510080, China"},{"name":"Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Guangzhou 510080, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6437-3653","authenticated-orcid":false,"given":"Zhijun","family":"Pan","sequence":"additional","affiliation":[{"name":"Department of Nutrition, School of Public Health, Sun Yat-sen University (Northern Campus), Guangzhou 510080, China"},{"name":"Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Guangzhou 510080, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhongxia","family":"Li","sequence":"additional","affiliation":[{"name":"BYHEALTH Institute of Nutrition and Health, Guangzhou 510663, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenhua","family":"Ling","sequence":"additional","affiliation":[{"name":"Department of Nutrition, School of Public Health, Sun Yat-sen University (Northern Campus), Guangzhou 510080, China"},{"name":"Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Guangzhou 510080, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,4,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1423","DOI":"10.1002\/hep.32499","article-title":"Are there outcome differences between NAFLD and metabolic-associated fatty liver disease?","volume":"76","author":"Younossi","year":"2022","journal-title":"Hepatology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/j.jhep.2022.08.030","article-title":"Alcohol consumption and metabolic syndrome: Clinical and epidemiological impact on liver disease","volume":"78","author":"Byrne","year":"2023","journal-title":"J. Hepatol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1335","DOI":"10.1097\/HEP.0000000000000004","article-title":"The global epidemiology of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH): A systematic review","volume":"77","author":"Younossi","year":"2023","journal-title":"Hepatology"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"851","DOI":"10.1016\/S2468-1253(22)00165-0","article-title":"The prevalence and incidence of NAFLD worldwide: A systematic review and meta-analysis","volume":"7","author":"Riazi","year":"2022","journal-title":"Lancet Gastroenterol. Hepatol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1016\/j.jhep.2023.03.017","article-title":"Global burden of liver disease: 2023 update","volume":"79","author":"Devarbhavi","year":"2023","journal-title":"J. Hepatol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"154170","DOI":"10.1016\/j.metabol.2020.154170","article-title":"Complications, morbidity and mortality of nonalcoholic fatty liver disease","volume":"111","author":"Mantovani","year":"2020","journal-title":"Metab. Clin. Exp."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1016\/j.cld.2023.01.007","article-title":"Economic Burden and Patient-Reported Outcomes of Nonalcoholic Fatty Liver Disease","volume":"27","author":"Stepanova","year":"2023","journal-title":"Clin. Liver Dis."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1541","DOI":"10.1007\/s00018-019-03011-w","article-title":"The links between the gut microbiome and non-alcoholic fatty liver disease (NAFLD)","volume":"76","author":"Safari","year":"2019","journal-title":"Cell. Mol. Life Sci. CMLS"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Vallianou, N., Christodoulatos, G.S., Karampela, I., Tsilingiris, D., Magkos, F., Stratigou, T., Kounatidis, D., and Dalamaga, M. (2021). Understanding the Role of the Gut Microbiome and Microbial Metabolites in Non-Alcoholic Fatty Liver Disease: Current Evidence and Perspectives. Biomolecules, 12.","DOI":"10.3390\/biom12010056"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Nassir, F. (2022). NAFLD: Mechanisms, Treatments, and Biomarkers. Biomolecules, 12.","DOI":"10.3390\/biom12060824"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Ji, Y., Yin, Y., Li, Z., and Zhang, W. (2019). Gut Microbiota-Derived Components and Metabolites in the Progression of Non-Alcoholic Fatty Liver Disease (NAFLD). Nutrients, 11.","DOI":"10.3390\/nu11081712"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1689","DOI":"10.1080\/10408398.2021.1966738","article-title":"Intestinal dysbiosis in nonalcoholic fatty liver disease (NAFLD): Focusing on the gut-liver axis","volume":"63","author":"Han","year":"2023","journal-title":"Crit. Rev. Food Sci. Nutr."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Imam, S.S., Alshehri, S., Ghoneim, M.M., Zafar, A., Alsaidan, O.A., Alruwaili, N.K., Gilani, S.J., and Rizwanullah, M. (2021). Recent Advancement in Chitosan-Based Nanoparticles for Improved Oral Bioavailability and Bioactivity of Phytochemicals: Challenges and Perspectives. Polymers, 13.","DOI":"10.3390\/polym13224036"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"8444","DOI":"10.1039\/D0FO01483D","article-title":"Phytochemicals as modifiers of gut microbial communities","volume":"11","author":"Dingeo","year":"2020","journal-title":"Food Funct."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Beane, K.E., Redding, M.C., Wang, X., Pan, J.H., Le, B., Cicalo, C., Jeon, S., Kim, Y.J., Lee, J.H., and Shin, E.-C. (2021). Effects of dietary fibers, micronutrients, and phytonutrients on gut microbiome: A review. Appl. Biol. Chem., 64.","DOI":"10.1186\/s13765-021-00605-6"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Kawabata, K., Yoshioka, Y., and Terao, J. (2019). Role of Intestinal Microbiota in the Bioavailability and Physiological Functions of Dietary Polyphenols. Molecules, 24.","DOI":"10.3390\/molecules24020370"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2656","DOI":"10.1038\/s41467-023-38259-1","article-title":"Resveratrol intervention attenuates chylomicron secretion via repressing intestinal FXR-induced expression of scavenger receptor SR-B1","volume":"14","author":"Pang","year":"2023","journal-title":"Nat. Commun."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1530","DOI":"10.1016\/j.cmet.2023.08.002","article-title":"Resistant starch decreases intrahepatic triglycerides in patients with NAFLD via gut microbiome alterations","volume":"35","author":"Ni","year":"2023","journal-title":"Cell Metab."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1002\/hep.29367","article-title":"The diagnosis and management of nonalcoholic fatty liver disease: Practice guidance from the American Association for the Study of Liver Diseases","volume":"67","author":"Chalasani","year":"2018","journal-title":"Hepatology"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1657","DOI":"10.1053\/j.gastro.2021.07.049","article-title":"Clinical Care Pathway for the Risk Stratification and Management of Patients With Nonalcoholic Fatty Liver Disease","volume":"161","author":"Kanwal","year":"2021","journal-title":"Gastroenterology"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"20190206","DOI":"10.1515\/jbcpp-2019-0206","article-title":"Silymarin: Not just another antioxidant","volume":"31","author":"Camini","year":"2020","journal-title":"J. Basic Clin. Physiol. Pharmacol."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Wadhwa, K., Pahwa, R., Kumar, M., Kumar, S., Sharma, P.C., Singh, G., Verma, R., Mittal, V., Singh, I., and Kaushik, D. (2022). Mechanistic Insights into the Pharmacological Significance of Silymarin. Molecules, 27.","DOI":"10.3390\/molecules27165327"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Bijak, M. (2017). Silybin, a Major Bioactive Component of Milk Thistle (Silybum marianum L. Gaernt.)-Chemistry, Bioavailability, and Metabolism. Molecules, 22.","DOI":"10.3390\/molecules22111942"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Perumpail, B.J., Li, A.A., Iqbal, U., Sallam, S., Shah, N.D., Kwong, W., Cholankeril, G., Kim, D., and Ahmed, A. (2018). Potential Therapeutic Benefits of Herbs and Supplements in Patients with NAFLD. Diseases, 6.","DOI":"10.3390\/diseases6030080"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1186\/s13063-023-07210-6","article-title":"Efficacy of silymarin in patients with non-alcoholic fatty liver disease\u2014The Siliver trial: A study protocol for a randomized controlled clinical trial","volume":"24","author":"Nunes","year":"2023","journal-title":"Trials"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1279","DOI":"10.1007\/s12325-020-01251-y","article-title":"Silymarin as Supportive Treatment in Liver Diseases: A Narrative Review","volume":"37","author":"Gillessen","year":"2020","journal-title":"Adv. Ther."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Munteanu, C., and Schwartz, B. (2023). The Effect of Bioactive Aliment Compounds and Micronutrients on Non-Alcoholic Fatty Liver Disease. Antioxidants, 12.","DOI":"10.3390\/antiox12040903"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2461","DOI":"10.1039\/C9FO00377K","article-title":"The chemical composition of a cold-pressed milk thistle seed flour extract, and its potential health beneficial properties","volume":"10","author":"Choe","year":"2019","journal-title":"Food Funct."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1111\/hepr.13444","article-title":"Changes of gut microbiota during silybin-mediated treatment of high-fat diet-induced non-alcoholic fatty liver disease in mice","volume":"50","author":"Li","year":"2020","journal-title":"Hepatol. Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1038\/s41467-023-36079-x","article-title":"Microbially produced vitamin B12 contributes to the lipid-lowering effect of silymarin","volume":"14","author":"Sun","year":"2023","journal-title":"Nat. Commun."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Cai, L., Gao, G., Yin, C., Bai, R., Li, Y., Sun, W., Pi, Y., Jiang, X., and Li, X. (2023). The Effects of Dietary Silybin Supplementation on the Growth Performance and Regulation of Intestinal Oxidative Injury and Microflora Dysbiosis in Weaned Piglets. Antioxidants, 12.","DOI":"10.3390\/antiox12111975"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"109099","DOI":"10.1016\/j.intimp.2022.109099","article-title":"Salvianolic acid B ameliorates non-alcoholic fatty liver disease by inhibiting hepatic lipid accumulation and NLRP3 inflammasome in ob\/ob mice","volume":"111","author":"Meng","year":"2022","journal-title":"Int. Immunopharmacol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"956688","DOI":"10.3389\/fimmu.2022.956688","article-title":"Puerarin ameliorates nonalcoholic fatty liver in rats by regulating hepatic lipid accumulation, oxidative stress, and inflammation","volume":"13","author":"Zhou","year":"2022","journal-title":"Front. Immunol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"e37052","DOI":"10.1097\/MD.0000000000037052","article-title":"Efficacy of traditional Chinese medicine combined with Silibinin on nonalcoholic fatty liver disease: A meta-analysis and systematic review","volume":"103","author":"Zhang","year":"2024","journal-title":"Medicine"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Bokoliya, S.C., Dorsett, Y., Panier, H., and Zhou, Y. (2021). Procedures for Fecal Microbiota Transplantation in Murine Microbiome Studies. Front. Cell. Infect. Microbiol., 11.","DOI":"10.3389\/fcimb.2021.711055"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Beisvag, V., J\u00fcnge, F.K., Bergum, H., J\u00f8lsum, L., Lydersen, S., G\u00fcnther, C.-C., Ramampiaro, H., Langaas, M., Sandvik, A.K., and L\u00e6greid, A. (2006). GeneTools\u2014Application for functional annotation and statistical hypothesis testing. BMC Bioinform., 7.","DOI":"10.1186\/1471-2105-7-470"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"i884","DOI":"10.1093\/bioinformatics\/bty560","article-title":"fastp: An ultra-fast all-in-one FASTQ preprocessor","volume":"34","author":"Chen","year":"2018","journal-title":"Bioinformatics"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1038\/nmeth.f.303","article-title":"QIIME allows analysis of high-throughput community sequencing data","volume":"7","author":"Caporaso","year":"2010","journal-title":"Nat. Methods"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1007\/978-1-0716-3072-3_3","article-title":"Metagenomics Databases for Bacteria","volume":"2649","author":"Wang","year":"2023","journal-title":"Methods Mol. Biol."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Segata, N., Izard, J., Waldron, L., Gevers, D., Miropolsky, L., Garrett, W.S., and Huttenhower, C. (2011). Metagenomic biomarker discovery and explanation. Genome Biol., 12.","DOI":"10.1186\/gb-2011-12-s1-p47"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"19913","DOI":"10.1038\/s41598-021-99389-4","article-title":"Applying PICRUSt and 16S rRNA functional characterisation to predicting co-digestion strategies of various animal manures for biogas production","volume":"11","author":"Ijoma","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Wen, B., Mei, Z., Zeng, C., and Liu, S. (2017). metaX: A flexible and comprehensive software for processing metabolomics data. BMC Bioinform., 18.","DOI":"10.1186\/s12859-017-1579-y"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"5976","DOI":"10.1039\/D0FO00795A","article-title":"Ameliorative effects and molecular mechanisms of vine tea on western diet-induced NAFLD","volume":"11","author":"Xie","year":"2020","journal-title":"Food Funct."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Huang, X., Chen, W., Yan, C., Yang, R., Chen, Q., Xu, H., and Huang, Y. (2019). Gypenosides improve the intestinal microbiota of non-alcoholic fatty liver in mice and alleviate its progression. Biomed. Pharmacother. Biomed. Pharmacother., 118.","DOI":"10.1016\/j.biopha.2019.109258"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1423","DOI":"10.1002\/ptr.3207","article-title":"Milk thistle in liver diseases: Past, present, future","volume":"24","author":"Abenavoli","year":"2010","journal-title":"Phytother. Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"109","DOI":"10.4254\/wjh.v5.i3.109","article-title":"Silymarin in non alcoholic fatty liver disease","volume":"5","author":"Cacciapuoti","year":"2013","journal-title":"World J. Hepatol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"204","DOI":"10.3390\/antiox4010204","article-title":"Silymarin as a Natural Antioxidant: An Overview of the Current Evidence and Perspectives","volume":"4","author":"Surai","year":"2015","journal-title":"Antioxidants"},{"key":"ref_48","first-page":"1940","article-title":"A Randomized Trial of Silymarin for the Treatment of Nonalcoholic Steatohepatitis","volume":"15","author":"Mahadeva","year":"2017","journal-title":"Clin. Gastroenterol. Hepatol. Off. Clin. Pract. J. Am. Gastroenterol. Assoc."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"8742075","DOI":"10.1155\/2019\/8742075","article-title":"Evaluation of the Effect Derived from Silybin with Vitamin D and Vitamin E Administration on Clinical, Metabolic, Endothelial Dysfunction, Oxidative Stress Parameters, and Serological Worsening Markers in Nonalcoholic Fatty Liver Disease Patients","volume":"2019","author":"Federico","year":"2019","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1658","DOI":"10.1016\/j.freeradbiomed.2012.02.008","article-title":"Silybin combined with phosphatidylcholine and vitamin E in patients with nonalcoholic fatty liver disease: A randomized controlled trial","volume":"52","author":"Loguercio","year":"2012","journal-title":"Free Radic. Biol. Med."},{"key":"ref_51","first-page":"5203","article-title":"Protective effect of salvianolic acid B on NASH rat liver through restoring intestinal mucosal barrier function","volume":"8","author":"Wang","year":"2015","journal-title":"Int. J. Clin. Exp. Pathol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1016\/j.arcmed.2017.11.016","article-title":"Regulation of SIRT3\/FOXO1 Signaling Pathway in Rats with Non-alcoholic Steatohepatitis by Salvianolic Acid B","volume":"48","author":"Wang","year":"2017","journal-title":"Arch. Med. Res."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Gong, M.J., Zhu, C.Y., Zou, Z.J., Han, B., and Huang, P. (2021). Therapeutic potential of puerarin against methionine-choline-deficient diet-induced non-alcoholic steatohepatitis determined by combination of (1)H NMR spectroscopy-based metabonomics and 16S rRNA gene sequencing. J. Pharm. Biomed. Anal., 197.","DOI":"10.1016\/j.jpba.2021.113964"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1186\/s12944-023-01969-y","article-title":"Puerarin ameliorates metabolic dysfunction-associated fatty liver disease by inhibiting ferroptosis and inflammation","volume":"22","author":"Yang","year":"2023","journal-title":"Lipids Health Dis."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Piko, P., Jenei, T., Kosa, Z., Sandor, J., Kovacs, N., Seres, I., Paragh, G., and Adany, R. (2023). Association of HDL Subfraction Profile with the Progression of Insulin Resistance. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241713563"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"2494","DOI":"10.2337\/db18-0474","article-title":"CETP Inhibition Improves HDL Function but Leads to Fatty Liver and Insulin Resistance in CETP-Expressing Transgenic Mice on a High-Fat Diet","volume":"67","author":"Zhu","year":"2018","journal-title":"Diabetes"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"799096","DOI":"10.3389\/fphys.2021.799096","article-title":"Expressing the Human Cholesteryl Ester Transfer Protein Minigene Improves Diet-Induced Fatty Liver and Insulin Resistance in Female Mice","volume":"12","author":"Zhu","year":"2021","journal-title":"Front. Physiol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/j.mce.2013.06.014","article-title":"Oleanolic acid improves hepatic insulin resistance via antioxidant, hypolipidemic and anti-inflammatory effects","volume":"376","author":"Wang","year":"2013","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"5531367","DOI":"10.1155\/2021\/5531367","article-title":"The Immunomodulating Effect of Baicalin on Inflammation and Insulin Resistance in High-Fat-Diet-Induced Obese Mice","volume":"2021","author":"Noh","year":"2021","journal-title":"Evid.-Based Complement. Altern. Med."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1038\/nrgastro.2017.119","article-title":"Bile acid-microbiota crosstalk in gastrointestinal inflammation and carcinogenesis","volume":"15","author":"Jia","year":"2018","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Ridlon, J.M., and Gaskins, H.R. (2024). Another renaissance for bile acid gastrointestinal microbiology. Nat. Rev. Gastroenterol. Hepatol.","DOI":"10.1038\/s41575-024-00896-2"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1469","DOI":"10.1099\/ijs.0.02873-0","article-title":"Akkermansia muciniphila gen. nov., sp. nov., a human intestinal mucin-degrading bacterium","volume":"54","author":"Derrien","year":"2004","journal-title":"Int. J. Syst. Evol. Microbiol."},{"key":"ref_63","first-page":"763","article-title":"Akkermansia muciniphila and Bifidobacterium bifidum Prevent NAFLD by Regulating FXR Expression and Gut Microbiota","volume":"11","author":"Nian","year":"2023","journal-title":"J. Clin. Transl. Hepatol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1875796","DOI":"10.1080\/19490976.2021.1875796","article-title":"Blautia\u2014A new functional genus with potential probiotic properties?","volume":"13","author":"Liu","year":"2021","journal-title":"Gut Microbes"},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"He, J., Zhang, P., Shen, L., Niu, L., Tan, Y., Chen, L., Zhao, Y., Bai, L., Hao, X., and Li, X. (2020). Short-Chain Fatty Acids and Their Association with Signalling Pathways in Inflammation, Glucose and Lipid Metabolism. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21176356"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1125","DOI":"10.1111\/1440-1681.13497","article-title":"Sodium butyrate ameliorates non-alcoholic fatty liver disease by upregulating miR-150 to suppress CXCR4 expression","volume":"48","author":"Zhang","year":"2021","journal-title":"Clin. Exp. Pharmacol. Physiol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"662","DOI":"10.1016\/j.chom.2015.03.005","article-title":"Crosstalk between Microbiota-Derived Short-Chain Fatty Acids and Intestinal Epithelial HIF Augments Tissue Barrier Function","volume":"17","author":"Kelly","year":"2015","journal-title":"Cell Host Microbe"},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Miao, W., Wu, X., Wang, K., Wang, W., Wang, Y., Li, Z., Liu, J., Li, L., and Peng, L. (2016). Sodium Butyrate Promotes Reassembly of Tight Junctions in Caco-2 Monolayers Involving Inhibition of MLCK\/MLC2 Pathway and Phosphorylation of PKC\u03b22. Int. J. Mol. Sci., 17.","DOI":"10.3390\/ijms17101696"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"7174","DOI":"10.1039\/C9FO01465A","article-title":"Altered short chain fatty acid profiles induced by dietary fiber intervention regulate AMPK levels and intestinal homeostasis","volume":"10","author":"Li","year":"2019","journal-title":"Food Funct."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"2398","DOI":"10.2337\/db14-1213","article-title":"Short-Chain Fatty Acids Protect Against High-Fat Diet-Induced Obesity via a PPAR\u03b3-Dependent Switch From Lipogenesis to Fat Oxidation","volume":"64","author":"Bleeker","year":"2015","journal-title":"Diabetes"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1017\/S0007114519001399","article-title":"Sodium butyrate protects against high-fat diet-induced oxidative stress in rat liver by promoting expression of nuclear factor E2-related factor 2","volume":"122","author":"Sun","year":"2019","journal-title":"Br. J. Nutr."},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Zhai, S., Qin, S., Li, L., Zhu, L., Zou, Z., and Wang, L. (2019). Dietary butyrate suppresses inflammation through modulating gut microbiota in high-fat diet-fed mice. FEMS Microbiol. Lett., 366.","DOI":"10.1093\/femsle\/fnz153"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1016\/j.cmet.2020.01.013","article-title":"Targeting Hepatic Glutaminase 1 Ameliorates Non-alcoholic Steatohepatitis by Restoring Very-Low-Density Lipoprotein Triglyceride Assembly","volume":"31","author":"Simon","year":"2020","journal-title":"Cell Metab."},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Mardinoglu, A., Bjornson, E., Zhang, C., Klevstig, M., S\u00f6derlund, S., St\u00e5hlman, M., Adiels, M., Hakkarainen, A., Lundbom, N., and Kilicarslan, M. (2017). Personal model-assisted identification of NAD(+) and glutathione metabolism as intervention target in NAFLD. Mol. Syst. Biol., 13.","DOI":"10.15252\/msb.20167422"},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Lo, E.K.K., Xu, J.-H., Zhan, Q., Zeng, Z., and El-Nezami, H. (2022). The Emerging Role of Branched-Chain Amino Acids in Liver Diseases. Biomedicines, 10.","DOI":"10.3390\/biomedicines10061444"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"e2200636","DOI":"10.1002\/mnfr.202200636","article-title":"Bile Acid Alterations Characterize the Early Onset and Progression of Nonalcoholic Fatty Liver Disease in Young Mice Fed with High Fat and Fructose Diet","volume":"67","author":"Xiang","year":"2023","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"H216","DOI":"10.1111\/1750-3841.13166","article-title":"High-fat Diet-induced Intestinal Hyperpermeability is Associated with Increased Bile Acids in the Large Intestine of Mice","volume":"81","author":"Murakami","year":"2016","journal-title":"J. Food Sci."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"7723","DOI":"10.1021\/acs.jafc.3c00952","article-title":"Dietary Isoquercetin Reduces Hepatic Cholesterol and Triglyceride in NAFLD Mice by Modulating Bile Acid Metabolism via Intestinal FXR-FGF15 Signaling","volume":"71","author":"Zhang","year":"2023","journal-title":"J. Agric. Food Chem."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"6862","DOI":"10.1038\/s41467-022-34671-1","article-title":"Disulfiram ameliorates nonalcoholic steatohepatitis by modulating the gut microbiota and bile acid metabolism","volume":"13","author":"Lei","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"134599","DOI":"10.1016\/j.foodchem.2022.134599","article-title":"Effect of lotus seed resistant starch on small intestinal flora and bile acids in hyperlipidemic rats","volume":"404","author":"Lei","year":"2023","journal-title":"Food Chem."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"678","DOI":"10.1038\/nrd2619","article-title":"Targeting bile-acid signalling for metabolic diseases","volume":"7","author":"Thomas","year":"2008","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"108238","DOI":"10.1016\/j.pharmthera.2022.108238","article-title":"Bile acid metabolism and signaling, the microbiota, and metabolic disease","volume":"237","author":"Cai","year":"2022","journal-title":"Pharmacol. Ther."},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Ni, Y., Lu, M., Xu, Y., Wang, Q., Gu, X., Li, Y., Zhuang, T., Xia, C., Zhang, T., and Gou, X.-J. (2022). The Role of Gut Microbiota-Bile Acids Axis in the Progression of Non-alcoholic Fatty Liver Disease. Front. Microbiol., 13.","DOI":"10.3389\/fmicb.2022.908011"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1152\/physrev.00010.2008","article-title":"Role of bile acids and bile acid receptors in metabolic regulation","volume":"89","author":"Lefebvre","year":"2009","journal-title":"Physiol. Rev."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1053\/j.gastro.2016.08.057","article-title":"An Intestinal Microbiota-Farnesoid X Receptor Axis Modulates Metabolic Disease","volume":"151","author":"Gonzalez","year":"2016","journal-title":"Gastroenterology"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.taap.2014.12.005","article-title":"Individual bile acids have differential effects on bile acid signaling in mice","volume":"283","author":"Song","year":"2015","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.cmet.2016.05.005","article-title":"Intestinal Crosstalk between Bile Acids and Microbiota and Its Impact on Host Metabolism","volume":"24","author":"Sayin","year":"2016","journal-title":"Cell Metab."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1103","DOI":"10.1038\/s41401-022-00880-z","article-title":"Bile acid and receptors: Biology and drug discovery for nonalcoholic fatty liver disease","volume":"43","author":"Jiao","year":"2022","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"1752","DOI":"10.1016\/j.cmet.2023.07.011","article-title":"Hyodeoxycholic acid alleviates non-alcoholic fatty liver disease through modulating the gut-liver axis","volume":"35","author":"Kuang","year":"2023","journal-title":"Cell Metab."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"4971","DOI":"10.1038\/s41467-019-12896-x","article-title":"Theabrownin from Pu-erh tea attenuates hypercholesterolemia via modulation of gut microbiota and bile acid metabolism","volume":"10","author":"Huang","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"1408","DOI":"10.1172\/JCI21025","article-title":"Bile acids lower triglyceride levels via a pathway involving FXR, SHP, and SREBP-1c","volume":"113","author":"Watanabe","year":"2004","journal-title":"J. Clin. Investig."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1671","DOI":"10.1016\/j.cmet.2021.06.012","article-title":"FXR activation protects against NAFLD via bile-acid-dependent reductions in lipid absorption","volume":"33","author":"Clifford","year":"2021","journal-title":"Cell Metab."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"609060","DOI":"10.3389\/fimmu.2020.609060","article-title":"TGR5 Regulates Macrophage Inflammation in Nonalcoholic Steatohepatitis by Modulating NLRP3 Inflammasome Activation","volume":"11","author":"Shi","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1159\/000450908","article-title":"Intestinal Farnesoid X Receptor Signaling Modulates Metabolic Disease","volume":"35","author":"Gonzalez","year":"2017","journal-title":"Dig. Dis."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"1881","DOI":"10.1136\/gutjnl-2017-314307","article-title":"Suppressed hepatic bile acid signalling despite elevated production of primary and secondary bile acids in NAFLD","volume":"67","author":"Jiao","year":"2018","journal-title":"Gut"},{"key":"ref_96","doi-asserted-by":"crossref","unstructured":"Katafuchi, T., and Makishima, M. (2022). Molecular Basis of Bile Acid-FXR-FGF15\/19 Signaling Axis. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23116046"},{"key":"ref_97","doi-asserted-by":"crossref","unstructured":"Ye, X., Huang, D., Dong, Z., Wang, X., Ning, M., Xia, J., Shen, S., Wu, S., Shi, Y., and Wang, J. (2022). FXR Signaling-Mediated Bile Acid Metabolism Is Critical for Alleviation of Cholesterol Gallstones by Lactobacillus Strains. Microbiol. Spectr., 10.","DOI":"10.1128\/spectrum.00518-22"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"12014","DOI":"10.1021\/acs.jafc.2c04817","article-title":"Nuciferine Protects Against High-Fat Diet-Induced Hepatic Steatosis via Modulation of Gut Microbiota and Bile Acid Metabolism in Rats","volume":"70","author":"Sun","year":"2022","journal-title":"J. Agric. Food Chem."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1172\/JCI76738","article-title":"Intestinal farnesoid X receptor signaling promotes nonalcoholic fatty liver disease","volume":"125","author":"Jiang","year":"2015","journal-title":"J. Clin. Investig."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"852","DOI":"10.1038\/s41586-024-07017-8","article-title":"Bile salt hydrolase acyltransferase activity expands bile acid diversity","volume":"626","author":"Guzior","year":"2024","journal-title":"Nature"}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/16\/8\/1169\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:27:53Z","timestamp":1760106473000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/16\/8\/1169"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,4,14]]},"references-count":100,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2024,4]]}},"alternative-id":["nu16081169"],"URL":"https:\/\/doi.org\/10.3390\/nu16081169","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,4,14]]}}}