{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:49:24Z","timestamp":1787028564201,"version":"build-2736575974"},"reference-count":60,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2025,6,10]],"date-time":"2025-06-10T00:00:00Z","timestamp":1749513600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Metabolic dysfunction-associated steatotic liver disease (MASLD) is a common cause of chronic liver disease and is closely associated with metabolic abnormalities and cardiovascular risks. Butyrate, a short-chain fatty acid produced by gut microbiota, has the potential to enhance liver health by modulating inflammation and supporting gut barrier integrity. This study aimed to investigate and compare the effects of sodium butyrate and calcium butyrate in patients with MASLD. In this single-center, randomized clinical trial, 181 patients with MASLD were enrolled and assigned to receive either sodium butyrate (n = 121) or calcium butyrate (n = 60) supplementation at a daily dose of 1000 mg. The primary endpoint was the change in liver steatosis, measured using the Controlled Attenuation Parameter (CAP) via FibroScan\u00ae. Secondary endpoints included liver stiffness, biochemical parameters, hepatic steatosis and fatty liver indices, fecal calprotectin levels, stool short-chain fatty acid levels, and microbiome composition. A subgroup analysis compared responders (a \u2265 5% reduction in CAP) to non-responders. There were no significant changes in CAP values for either group (\u0394CAP: sodium butyrate, 0.84; calcium butyrate, \u22120.23; p = 0.70). Sodium butyrate significantly reduced serum trimethylamine N-oxide and fatty liver index, while calcium butyrate led to a decrease in fecal calprotectin levels. Responders demonstrated a lower body mass index, higher levels of high-sensitivity C-reactive protein and HbA1c, and distinct microbiome profiles, characterized by lower abundance of Subdoligranulum and higher abundance of Catenibacterium. Although butyrate supplementation did not significantly improve liver steatosis as measured by CAP, the differing effects on metabolic and inflammatory markers suggest that there may be potential benefits for specific subgroups of patients with MASLD.<\/jats:p>","DOI":"10.3390\/ijms26125561","type":"journal-article","created":{"date-parts":[[2025,6,10]],"date-time":"2025-06-10T12:53:16Z","timestamp":1749559996000},"page":"5561","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Exploring the Potential of Oral Butyrate Supplementation in Metabolic Dysfunction-Associated Steatotic Liver Disease: Subgroup Insights from an Interventional Study"],"prefix":"10.3390","volume":"26","author":[{"given":"Milo\u0161","family":"Mitrovi\u0107","sequence":"first","affiliation":[{"name":"Department of Gastroenterology, University Medical Center Zvezdara, 11080 Belgrade, Serbia"},{"name":"School of Medicine, Belgrade University, 11080 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Verica","family":"Stankovi\u0107 Popovi\u0107","sequence":"additional","affiliation":[{"name":"School of Medicine, Belgrade University, 11080 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7229-9406","authenticated-orcid":false,"given":"Sanja","family":"Erceg","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy, Department of Medical Biochemistry, Belgrade University, 11080 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Milena","family":"Peri\u0161i\u0107 Mitrovi\u0107","sequence":"additional","affiliation":[{"name":"School of Medicine, Belgrade University, 11080 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"Dobrosavljevi\u0107","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, University Medical Center Zvezdara, 11080 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrej","family":"Stupar","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, University Medical Center Zvezdara, 11080 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petra","family":"Vukovi\u0107","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, University Medical Center Zvezdara, 11080 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Du\u0161an","family":"Zlatkovi\u0107","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, University Medical Center Zvezdara, 11080 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petar","family":"Svorcan","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, University Medical Center Zvezdara, 11080 Belgrade, Serbia"},{"name":"School of Medicine, Belgrade University, 11080 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2809","DOI":"10.1016\/j.cgh.2021.12.002","article-title":"2019 Global NAFLD prevalence: A systematic review and meta-analysis","volume":"20","author":"Le","year":"2022","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_2","first-page":"691","article-title":"MASLD: A systemic metabolic disorder with cardiovascular and malignant complications","volume":"73","author":"Targher","year":"2024","journal-title":"Gut"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1080\/1744666X.2023.2294046","article-title":"The pathophysiology of MASLD: An immunometabolic perspective","volume":"20","author":"Grabherr","year":"2024","journal-title":"Expert Rev. Clin. Immunol."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Vallianou, N.G., Kounatidis, D., Psallida, S., Vythoulkas-Biotis, N., Adamou, A., Zachariadou, T., Kargioti, S., Karampela, I., and Dalamaga, M. (2024). NAFLD\/MASLD and the Gut-Liver Axis: From Pathogenesis to Treatment Options. Metabolites, 14.","DOI":"10.3390\/metabo14070366"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Li, X., Hong, J., Wang, Y., Pei, M., Wang, L., and Gong, Z. (2021). Trimethylamine-N-Oxide Pathway: A Potential Target for the Treatment of MAFLD. Front. Mol. Biosci., 8.","DOI":"10.3389\/fmolb.2021.733507"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Amiri, P., Arefhosseini, S., Bakhshimoghaddam, F., Jamshidi Gurvan, H., and Hosseini, S.A. (2022). Mechanistic insights into the pleiotropic effects of butyrate as a potential therapeutic agent on NAFLD management: A systematic review. Front. Nutr., 9.","DOI":"10.3389\/fnut.2022.1037696"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Fusco, W., Lorenzo, M.B., Cintoni, M., Porcari, S., Rinninella, E., Kaitsas, F., Lener, E., Mele, M.C., Gasbarrini, A., and Collado, M.C. (2023). Short-Chain Fatty-Acid-Producing Bacteria: Key Components of the Human Gut Microbiota. Nutrients, 15.","DOI":"10.3390\/nu15092211"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Yan, H., and Ajuwon, K.M. (2017). Butyrate modifies intestinal barrier function in IPEC-J2 cells through a selective upregulation of tight junction proteins and activation of the Akt signaling pathway. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0179586"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1016\/j.jcmgh.2021.05.006","article-title":"Sodium Butyrate Supplementation Inhibits Hepatic Steatosis by Stimulating Liver Kinase B1 and Insulin-Induced Gene","volume":"12","author":"Zhao","year":"2021","journal-title":"Cell. Mol. Gastroenterol. Hepatol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1016\/j.cmet.2011.03.009","article-title":"AMPK phosphorylates and inhibits SREBP activity to attenuate hepatic steatosis and atherosclerosis in diet-induced insulin-resistant mice","volume":"13","author":"Li","year":"2011","journal-title":"Cell Metab."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s12276-018-0183-1","article-title":"Sodium butyrate reduces high-fat diet-induced non-alcoholic steatohepatitis through upregulation of hepatic GLP-1R expression","volume":"50","author":"Zhou","year":"2018","journal-title":"Exp. Mol. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1016\/j.redox.2017.03.006","article-title":"Butyrate induces ROS-mediated apoptosis by modulating miR-22\/SIRT-1 pathway in hepatic cancer cells","volume":"12","author":"Pant","year":"2017","journal-title":"Redox Biol."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Fogacci, F., Giovannini, M., Di Micoli, V., Grandi, E., Borghi, C., and Cicero, A.F.G. (2024). Effect of Supplementation of a Butyrate-Based Formula in Individuals with Liver Steatosis and Metabolic Syndrome: A Randomized Double-Blind Placebo-Controlled Clinical Trial. Nutrients, 16.","DOI":"10.3390\/nu16152454"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1016\/j.dld.2009.08.002","article-title":"Hepatic steatosis index: A simple screening tool reflecting nonalcoholic fatty liver disease","volume":"42","author":"Lee","year":"2010","journal-title":"Dig. Liver Dis."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Bedogni, G., Bellentani, S., Miglioli, L., Masutti, F., Passalacqua, M., Castiglione, A., and Tiribelli, C. (2006). The Fatty Liver Index: A simple and accurate predictor of hepatic steatosis in the general population. BMC Gastroenterol., 6.","DOI":"10.1186\/1471-230X-6-33"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Blanco-Grau, A., Gabriel-Medina, P., Rodriguez-Algarra, F., Villena, Y., Lopez-Mart\u00ednez, R., August\u00edn, S., Pons, M., Cruz, L.M., Rando-Segura, A., and Enfedaque, B. (2021). Assessing Liver Fibrosis Using the FIB4 Index in the Community Setting. Diagnostics, 11.","DOI":"10.3390\/diagnostics11122236"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1219","DOI":"10.3748\/wjg.v19.i8.1219","article-title":"NAFLD fibrosis score: A prognostic predictor for mortality and liver complications among NAFLD patients","volume":"19","author":"Treeprasertsuk","year":"2013","journal-title":"World J. Gastroenterol."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Biciusca, T., Stan, S.I., Balteanu, M.A., Cioboata, R., Ghenea, A.E., Danoiu, S., Bumbea, A.M., and Biciusca, V. (2023). The Role of the Fatty Liver Index (FLI) in the Management of Non-Alcoholic Fatty Liver Disease: A Systematic Review. Diagnostics, 13.","DOI":"10.3390\/diagnostics13213316"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"e43073","DOI":"10.1016\/j.heliyon.2025.e43073","article-title":"Comparing non-alcoholic fatty liver disease indices in predicting the prevalence and incidence of metabolic syndrome in middle-aged adults","volume":"7","author":"Kim","year":"2025","journal-title":"Heliyon"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"156082","DOI":"10.1016\/j.metabol.2024.156082","article-title":"Accurate non-invasive detection of MASH with fibrosis F2-F3 using a lightweight machine learning model with minimal clinical and metabolomic variables","volume":"163","author":"Stefanakis","year":"2025","journal-title":"Metabolism"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"704","DOI":"10.1016\/S2468-1253(23)00141-3","article-title":"Performance of non-invasive tests and histology for the prediction of clinical outcomes in patients with non-alcoholic fatty liver disease: An individual participant data meta-analysis","volume":"8","author":"Lee","year":"2023","journal-title":"Lancet Gastroenterol. Hepatol."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Jaworska, K., Kopacz, W., Koper, M., and Ufnal, M. (2024). Microbiome-Derived Trimethylamine N-Oxide (TMAO) as a Multifaceted Biomarker in Cardiovascular Disease: Challenges and Opportunities. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms252312511"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Eyileten, C., Jarosz-Popek, J., Jakubik, D., Gasecka, A., Wolska, M., Ufnal, M., Postula, M., Toma, A., Lang, I.M., and Siller-Matula, J.M. (2021). Plasma Trimethylamine-N-Oxide Is an Independent Predictor of Long-Term Cardiovascular Mortality in Patients Undergoing Percutaneous Coronary Intervention for Acute Coronary Syndrome. Front. Cardiovasc. Med., 8.","DOI":"10.3389\/fcvm.2021.728724"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"3318","DOI":"10.1007\/s10620-015-3776-8","article-title":"Altered Bile Acid Metabolome in Patients with Nonalcoholic Steatohepatitis","volume":"60","author":"Ferslew","year":"2015","journal-title":"Dig. Dis. Sci."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Calder\u00f3n-P\u00e9rez, L., Gosalbes, M.J., Yuste, S., Valls, R.M., Pedret, A., Llaurad\u00f3, E., Jimenez-Hernandez, N., Artacho, A., Pla-Pag\u00e0, L., and Companys, J. (2020). Gut metagenomic and short chain fatty acids signature in hypertension: A cross-sectional study. Sci. Rep., 10.","DOI":"10.1038\/s41598-020-63475-w"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1978","DOI":"10.1136\/gutjnl-2021-324855","article-title":"Calprotectin: From biomarker to biological function","volume":"70","author":"Jukic","year":"2021","journal-title":"Gut"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Heinzel, S., Jureczek, J., Kainulainen, V., Nieminen, A.I., Suenkel, U., von Thaler, A.K., Kaleta, C., Eschweiler, G.W., Brockmann, K., and Aho, V.T.E. (2024). Elevated fecal calprotectin is associated with gut microbial dysbiosis, altered serum markers and clinical outcomes in older individuals. Sci. Rep., 14.","DOI":"10.1038\/s41598-024-63893-0"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1186\/s12944-024-02203-z","article-title":"Effects of short-chain fatty acid-butyrate supplementation on expression of circadian-clock genes, sleep quality, and inflammation in patients with active ulcerative colitis: A double-blind randomized controlled trial","volume":"23","author":"Firoozi","year":"2024","journal-title":"Lipids Health Dis."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Tougaard, N.H., Frimodt-M\u00f8ller, M., Salmenkari, H., Stougaard, E.B., Zawadzki, A.D., Mattila, I.M., Hansen, T.W., Legido-Quigley, C., H\u00f6rkk\u00f6, S., and Forsblom, C. (2022). Effects of Butyrate Supplementation on Inflammation and Kidney Parameters in Type 1 Diabetes: A Randomized, Double-Blind, Placebo-Controlled Trial. J. Clin. Med., 11.","DOI":"10.3390\/jcm11133573"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"3151","DOI":"10.1021\/jf3001058","article-title":"In Vitro Dissolution and in Vivo Absorption of Calcium [1-14C] Butyrate in Free or Protected Forms","volume":"60","author":"Smith","year":"2012","journal-title":"J. Agric. Food Chem."},{"key":"ref_31","first-page":"e71451","article-title":"Diagnosis and Management of Lean Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD): A Systematic Review","volume":"16","author":"Njei","year":"2024","journal-title":"Cureus"},{"key":"ref_32","unstructured":"Freeman, A.M., Acevedo, L.A., and Pennings, N. (2025). Insulin Resistance. StatPearls [Internet], StatPearls Publishing."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"835","DOI":"10.2147\/CIA.S132940","article-title":"Relationship between sarcopenia and physical activity in older people: A systematic review and meta-analysis","volume":"12","author":"Steffl","year":"2017","journal-title":"Clin. Interv. Aging"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1016\/j.jceh.2021.06.011","article-title":"Lean Fatty Liver Disease: Through Thick and Thin","volume":"11","author":"Premkumar","year":"2021","journal-title":"J. Clin. Exp. Hepatol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"776","DOI":"10.1002\/hep.28376","article-title":"Sarcopenia is associated with significant liver fibrosis independently of obesity and insulin resistance in nonalcoholic fatty liver disease: Nationwide surveys (KNHANES 2008\u20132011)","volume":"63","author":"Lee","year":"2016","journal-title":"Hepatology"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Cri\u015fan, D., Avram, L., Morariu-Barb, A., Grapa, C., Hiri\u015fcau, I., Cr\u0103ciun, R., Donca, V., and Neme\u015f, A. (2025). Sarcopenia in MASLD-Eat to Beat Steatosis, Move to Prove Strength. Nutrients, 17.","DOI":"10.3390\/nu17010178"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1111\/j.1462-8902.2003.0342.x","article-title":"Relationship between C-reactive protein and visceral adipose tissue in healthy Japanese subjects","volume":"6","author":"Saijo","year":"2004","journal-title":"Diabetes Obes. Metab."},{"key":"ref_38","first-page":"1","article-title":"From correlation to causality: The case of Subdoligranulum","volume":"12","author":"Prifti","year":"2020","journal-title":"Gut Microbes"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1099\/jmm.0.017541-0","article-title":"Butyric acid-producing anaerobic bacteria as a novel probiotic treatment approach for inflammatory bowel disease","volume":"59","author":"Ducatelle","year":"2010","journal-title":"J. Med. Microbiol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"E4485","DOI":"10.1073\/pnas.1415174111","article-title":"Intestinal permeability, gut-bacterial dysbiosis, and behavioral markers of alcohol-dependence severity","volume":"111","author":"Leclercq","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Louis, S., Tappu, R.M., Damms-Machado, A., Huson, D.H., and Bischoff, S.C. (2016). Characterization of the Gut Microbial Community of Obese Patients Following a Weight-Loss Intervention Using Whole Metagenome Shotgun Sequencing. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0149564"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1007\/s13300-017-0226-y","article-title":"Effects of Acarbose on the Gut Microbiota of Prediabetic Patients: A Randomized, Double-blind, Controlled Crossover Trial","volume":"8","author":"Zhang","year":"2017","journal-title":"Diabetes Ther."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Lee, C.B., Chae, S.U., Jo, S.J., Jerng, U.M., and Bae, S.K. (2021). The Relationship between the Gut Microbiome and Metformin as a Key for Treating Type 2 Diabetes Mellitus. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22073566"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"2282795","DOI":"10.1080\/19490976.2023.2282795","article-title":"Gut microbiome and frailty: Insight from genetic correlation and mendelian randomization","volume":"15","author":"Cui","year":"2023","journal-title":"Gut Microbes"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"P\u00e9rez-Matute, P., \u00cd\u00f1iguez, M., Villanueva-Mill\u00e1n, M.J., and Oteo, J.A. (2019). Chapter 32\u2014The oral, genital and gut microbiome in HIV infection. Microbiome and Metabolome in Diagnosis, Therapy, and other Strategic Applications, Academic Press.","DOI":"10.1016\/B978-0-12-815249-2.00032-4"},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Borges, N.A., and Mafra, D. (2018). The Gut Microbiome in Chronic Kidney Disease. Microbiome and Metabolome in Diagnosis, Therapy, and Other Strategic Applications, Academic Press.","DOI":"10.1016\/B978-0-12-815249-2.00036-1"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1590\/0100-3984.2019.0028","article-title":"Ultrasound elastography in patients with fatty liver disease","volume":"53","author":"Tochetto","year":"2020","journal-title":"Radiol. Bras."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Ruggeri, S., Buonocore, P., and Amoriello, T. (2022). New Validated Short Questionnaire for the Evaluation of the Adherence of Mediterranean Diet and Nutritional Sustainability in All Adult Population Groups. Nutrients, 14.","DOI":"10.3390\/nu14235177"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.jchromb.2016.10.017","article-title":"Determination of trimethylamine, trimethylamine N-oxide, and taurine in human plasma and urine by UHPLC-MS\/MS technique","volume":"1038","author":"Awwad","year":"2016","journal-title":"J. Chromatogr. B Analyt Technol. Biomed. Life Sci."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1093\/ajcn\/46.4.641","article-title":"Fecal short-chain fatty acid (SCFA) analysis by capillary gas-liquid chromatography","volume":"46","author":"Scheppach","year":"1987","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1016\/0009-9120(96)00044-6","article-title":"Automation of toxicological screenings on a Hewlett Packard Chemstation GC-MS system","volume":"29","author":"Fiers","year":"1996","journal-title":"Clin. Biochem."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1621","DOI":"10.1038\/ismej.2012.8","article-title":"Ultra-high-throughput microbial community analysis on the Illumina HiSeq and MiSeq platforms","volume":"6","author":"Caporaso","year":"2012","journal-title":"ISME J."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"996","DOI":"10.1038\/nmeth.2604","article-title":"UPARSE: Highly accurate OTU sequences from microbial amplicon reads","volume":"10","author":"Edgar","year":"2013","journal-title":"Nat. Methods"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"5261","DOI":"10.1128\/AEM.00062-07","article-title":"Naive Bayesian classifier for rapid assignment of rRNA sequences into the new bacterial taxonomy","volume":"73","author":"Wang","year":"2007","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"D590","DOI":"10.1093\/nar\/gks1219","article-title":"The SILVA ribosomal RNA gene database project: Improved data processing and web-based tools","volume":"41","author":"Quast","year":"2013","journal-title":"Nucleic Acids Res."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1097\/00002508-198712000-00003","article-title":"Measurement of pain: A comparison of the visual analogue with a nonvisual analogue scale","volume":"3","author":"Murphy","year":"1987","journal-title":"Clin. J. Pain"},{"key":"ref_57","unstructured":"Raosoft Software (2023, December 01). Calculate Your Sample Size. Available online: http:\/\/www.raosoft.com\/samplesize.html."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Ferro, Y., Montalcini, T., Mazza, E., Foti, D., Angotti, E., Gliozzi, M., Nucera, S., Paone, S., Bombardelli, E., and Aversa, I. (2020). Randomized Clinical Trial: Bergamot Citrus and Wild Cardoon Reduce Liver Steatosis and Body Weight in Non-diabetic Individuals Aged Over 50 Years. Front. Endocrinol., 11.","DOI":"10.3389\/fendo.2020.00494"},{"key":"ref_59","first-page":"184","article-title":"The effects of synbiotics on the liver steatosis, inflammation, and gut microbiome of metabolic dysfunction-associated liver disease patients-randomized trial","volume":"62","author":"Kralj","year":"2024","journal-title":"Rom. J. Intern. Med."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1111\/dom.13520","article-title":"Evaluation of the effects of dapagliflozin, a sodium-glucose co-transporter-2 inhibitor, on hepatic steatosis and fibrosis using transient elastography in patients with type 2 diabetes and non-alcoholic fatty liver disease","volume":"21","author":"Shimizu","year":"2019","journal-title":"Diabetes Obes. Metab."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/12\/5561\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:49:39Z","timestamp":1760032179000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/12\/5561"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,10]]},"references-count":60,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2025,6]]}},"alternative-id":["ijms26125561"],"URL":"https:\/\/doi.org\/10.3390\/ijms26125561","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,10]]}}}