{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T22:09:29Z","timestamp":1788473369945,"version":"build-2803163510"},"reference-count":73,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T00:00:00Z","timestamp":1772582400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005699","name":"University of Eastern Piedmont","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100005699","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Type 2 Diabetes Mellitus (T2DM) is a chronic metabolic disorder linked to gut microbiota dysbiosis and impaired inter-organ metabolic signalling. This study investigated the combined effects of the probiotic Lactiplantibacillus plantarum TJA7 and Mulberry Leaf extract (Morus alba) on cellular processes relevant to T2DM-related metabolic dysfunction. An advanced in vitro gut\u2013pancreas\u2013liver axis model, using Caco-2, EndoC-\u03b2H5, and HepG2 cells, was employed under hyperglycemic and oxidative stress conditions. The combined treatment consistently outperformed the individual components by improving intestinal barrier integrity, as indicated by increased transepithelial electrical resistance (TEER), and by enhancing butyrate translocation across the intestinal layer. Metabolites derived from the combination attenuated pancreatic \u03b2-cell dysfunction, reducing reactive oxygen species (ROS) levels and increased insulin secretion (1.7-fold compared with Mulberry Leaf extract alone). At the hepatic level, co-administration modulated key glucose metabolism pathways, including Insulin Receptor Substrate 1 (IRS1), Protein Kinase B (AKT), AMP-Activated Protein Kinase (AMPK), and Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1 Alpha (PGC-1\u03b1), suggesting improved cellular glucose handling. Collectively, these findings support a positive dose-specific interaction under the tested conditions and provide a biologically plausible, hypothesis-generating framework for probiotic\u2013phytochemical cooperation along the gut\u2013pancreas\u2013liver axis. Further in vivo and clinical studies are required to establish causality and translational relevance.<\/jats:p>","DOI":"10.3390\/ijms27052375","type":"journal-article","created":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T08:51:33Z","timestamp":1772614293000},"page":"2375","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["A Combined Probiotic-Morus alba Strategy Enhances Glucose Homeostasis in an In Vitro Gut-Pancreas-Liver Axis Model: A Preliminary Mechanistic Screening Study"],"prefix":"10.3390","volume":"27","author":[{"given":"Francesca","family":"Parini","sequence":"first","affiliation":[{"name":"Noivita S.r.l.s., Spin Off of University of Piemonte Orientale, Strada Privata Curti n. 7, 28100 Novara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca","family":"Galla","sequence":"additional","affiliation":[{"name":"Noivita S.r.l.s., Spin Off of University of Piemonte Orientale, Strada Privata Curti n. 7, 28100 Novara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simone","family":"Mul\u00e8","sequence":"additional","affiliation":[{"name":"Laboratory of Physiology, Department for Sustainable Development and Ecological Transition, University of Piemonte Orientale, UPO, 13100 Vercelli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matteo","family":"Musu","sequence":"additional","affiliation":[{"name":"Laboratory of Physiology, Department for Sustainable Development and Ecological Transition, University of Piemonte Orientale, UPO, 13100 Vercelli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5751-270X","authenticated-orcid":false,"given":"Francesca","family":"Uberti","sequence":"additional","affiliation":[{"name":"Laboratory of Physiology, Department for Sustainable Development and Ecological Transition, University of Piemonte Orientale, UPO, 13100 Vercelli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e1900457","DOI":"10.1002\/mnfr.201900457","article-title":"Ameliorative Effects of Probiotic Lactobacillus paracasei NL41 on Insulin Sensitivity, Oxidative Stress, and Beta-Cell Function in a Type 2 Diabetes Mellitus Rat Model","volume":"63","author":"Zeng","year":"2019","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/S2213-8587(25)00299-2","article-title":"11th edition of the IDF Diabetes Atlas: Global, regional, and national diabetes prevalence estimates for 2024 and projections for 2050","volume":"14","author":"Genitsaridi","year":"2025","journal-title":"Lancet Diabetes Endocrinol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"269","DOI":"10.5001\/omj.2012.68","article-title":"Type 2 diabetes mellitus: A review of current trends","volume":"27","author":"Olokoba","year":"2012","journal-title":"Oman Med. J."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Galicia-Garcia, U., Benito-Vicente, A., Jebari, S., Larrea-Sebal, A., Siddiqi, H., Uribe, K.B., Ostolaza, H., and Mart\u00edn, C. (2020). Pathophysiology of Type 2 Diabetes Mellitus. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21176275"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Bellou, V., Belbasis, L., Tzoulaki, I., and Evangelou, E. (2018). Risk factors for type 2 diabetes mellitus: An exposure-wide umbrella review of meta-analyses. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0194127"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1111\/cge.13772","article-title":"Genetic predisposition in type 2 diabetes: A promising approach toward a personalized management of diabetes","volume":"98","author":"Sirdah","year":"2020","journal-title":"Clin. Genet."},{"key":"ref_7","first-page":"e7614","article-title":"The Pathophysiology of Type 2 Diabetes Mellitus in Non-obese Individuals: An Overview of the Current Understanding","volume":"12","author":"Olaogun","year":"2020","journal-title":"Cureus"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"526","DOI":"10.1203\/PDR.0b013e3181d4ff2b","article-title":"Effects of probiotics, prebiotics, and synbiotics on messenger RNA expression of caveolin-1, NOS, and genes regulating oxidative stress in the terminal ileum of formula-fed neonatal rats","volume":"67","author":"Fordjour","year":"2010","journal-title":"Pediatr. Res."},{"key":"ref_9","first-page":"45","article-title":"Type 2 diabetes mellitus, oxidative stress and inflammation: Examining the links","volume":"11","author":"Oguntibeju","year":"2019","journal-title":"Int. J. Physiol. Pathophysiol. Pharmacol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/j.diabres.2019.03.024","article-title":"Treatment of type 2 diabetes mellitus worldwide: Baseline patient characteristics in the global DISCOVER study","volume":"151","author":"Gomes","year":"2019","journal-title":"Diabetes Res. Clin. Pract."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"102590","DOI":"10.1016\/j.ebiom.2019.11.051","article-title":"Role of gut microbiota in type 2 diabetes pathophysiology","volume":"51","author":"Gurung","year":"2020","journal-title":"EBioMedicine"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Sikalidis, A.K., and Maykish, A. (2020). The Gut Microbiome and Type 2 Diabetes Mellitus: Discussing a Complex Relationship. Biomedicines, 8.","DOI":"10.3390\/biomedicines8010008"},{"key":"ref_13","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_14","doi-asserted-by":"crossref","first-page":"2459","DOI":"10.1007\/s00018-020-03710-9","article-title":"Modeling different types of diabetes using human pluripotent stem cells","volume":"78","author":"Abdelalim","year":"2021","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Chakaroun, R.M., Massier, L., and Kovacs, P. (2020). Gut Microbiome, Intestinal Permeability, and Tissue Bacteria in Metabolic Disease: Perpetrators or Bystanders?. Nutrients, 12.","DOI":"10.3390\/nu12041082"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"104","DOI":"10.33590\/emjdiabet\/10310327","article-title":"Role of probiotics in diabetes: A review of their rationale and efficacy","volume":"5","author":"Shah","year":"2017","journal-title":"EMJ Diabet."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"100093","DOI":"10.1016\/j.metop.2021.100093","article-title":"Probiotic and resveratrol normalize GLP-1 levels and oxidative stress in the intestine of diabetic rats","volume":"10","author":"Pegah","year":"2021","journal-title":"Metabol. Open"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"e0061520","DOI":"10.1128\/IAI.00615-20","article-title":"Lactobacillus plantarum Reduces Low-Grade Inflammation and Glucose Levels in a Mouse Model of Chronic Stress and Diabetes","volume":"89","author":"Youn","year":"2021","journal-title":"Infect. Immun."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"S6","DOI":"10.1016\/j.sjbs.2015.09.022","article-title":"In vitro importance of probiotic Lactobacillus plantarum related to medical field","volume":"23","author":"Arasu","year":"2016","journal-title":"Saudi J. Biol. Sci."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/j.ejmech.2015.08.043","article-title":"Re-exploring promising \u03b1-glucosidase inhibitors for potential development into oral anti-diabetic drugs: Finding needle in the haystack","volume":"103","author":"Ghani","year":"2015","journal-title":"Eur. J. Med. Chem."},{"key":"ref_21","first-page":"554","article-title":"Physiological Characteristics and Anti-obesity Effect of Lactobacillus plantarum K10","volume":"38","author":"Kim","year":"2018","journal-title":"Korean J. Food Sci. Anim. Resour."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"3181","DOI":"10.1007\/s00284-021-02588-5","article-title":"In Vitro Antidiabetic, Antioxidant Activity, and Probiotic Activities of Lactiplantibacillus plantarum and Lacticaseibacillus paracasei Strains","volume":"78","author":"Won","year":"2021","journal-title":"Curr. Microbiol."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Wang, P., Liang, Y., Chen, K., Yau, S.Y., Sun, X., Cheng, K.K., Xu, A., So, K.F., and Li, A. (2020). Potential Involvement of Adiponectin Signaling in Regulating Physical Exercise-Elicited Hippocampal Neurogenesis and Dendritic Morphology in Stressed Mice. Front. Cell. Neurosci., 14.","DOI":"10.3389\/fncel.2020.00189"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1981","DOI":"10.1016\/j.bbamem.2015.05.003","article-title":"Equilibrium binding behavior of magnesium to wall teichoic acid","volume":"1848","author":"Thomas","year":"2015","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"620","DOI":"10.1007\/s12010-011-9453-2","article-title":"Lactobacillus plantarum AS1 isolated from south Indian fermented food Kallappam suppress 1,2-dimethyl hydrazine (DMH)-induced colorectal cancer in male Wistar rats","volume":"166","author":"Kumar","year":"2012","journal-title":"Appl. Biochem. Biotechnol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"131","DOI":"10.7813\/2075-4124.2012\/4-6\/A.19","article-title":"Antioxidant activity and biological evaluations of probiotic bacteria strains","volume":"4","author":"Afify","year":"2012","journal-title":"Int. J. Acad. Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.foodres.2014.01.010","article-title":"Adhesion abilities of dairy Lactobacillus plantarum strains showing an aggregation phenotype","volume":"57","author":"Korany","year":"2014","journal-title":"Food Res. Int."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"106864","DOI":"10.1016\/j.jff.2025.106864","article-title":"Lactiplantibacillus plantarum in fermented beverages: Properties, mechanisms, and future prospects","volume":"129","author":"Lin","year":"2025","journal-title":"J. Funct. Foods"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Lown, M., Fuller, R., Lightowler, H., Fraser, A., Gher, A., Stuart, B., Byrne, C., and Lewith, G. (2017). Mulberry-extract improves glucose tolerance and decreases insulin concentrations in normoglycaemic adults: Results of a randomised double-blind placebo-controlled study. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0172239"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"116143","DOI":"10.1016\/j.jep.2023.116143","article-title":"Clinical potential and mechanistic insights of mulberry (Morus alba L.) leaves in managing type 2 diabetes mellitus: Focusing on gut microbiota, inflammation, and metabolism","volume":"306","author":"Tang","year":"2023","journal-title":"J. Ethnopharmacol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1022","DOI":"10.12688\/f1000research.55573.1","article-title":"Medicinal properties of Morus alba for the control of type 2 diabetes mellitus: A systematic review","volume":"10","year":"2021","journal-title":"F1000Research"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2207","DOI":"10.20546\/ijcmas.2017.607.259","article-title":"Biochemical Composition and Pharmacological Properties of Mulberry (Morus spp.)\u2014A Review","volume":"6","author":"Mahesh","year":"2017","journal-title":"Int. J. Curr. Microbiol. Appl. Sci."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Hoffmann, P., Burmester, M., Langeheine, M., Brehm, R., Empl, M.T., Seeger, B., and Breves, G. (2021). Caco-2\/HT29-MTX co-cultured cells as a model for studying physio-logical properties and toxin-induced effects on intestinal cells. PLoS ONE, 16.","DOI":"10.1371\/journal.pone.0257824"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Li, H.Y., Zhou, D.D., Gan, R.Y., Huang, S.Y., Zhao, C.N., Shang, A., Xu, X.Y., and Li, H.B. (2021). Effects and Mechanisms of Probiotics, Prebiotics, Synbiotics, and Postbiotics on Metabolic Diseases Targeting Gut Microbiota: A Narrative Review. Nutrients, 13.","DOI":"10.3390\/nu13093211"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1186\/s12967-023-04306-0","article-title":"The effects of probiotics supplementation on glycaemic control among adults with type 2 diabetes mellitus: A systematic review and meta-analysis of randomised clinical trials","volume":"21","author":"Li","year":"2023","journal-title":"J. Transl. Med."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"6690","DOI":"10.1007\/s12010-024-04879-6","article-title":"A dual therapeutic approach to diabetes mellitus via bioactive phytochemicals found in a poly herbal extract by restoration of favorable gut flora and related short-chain fatty acids","volume":"196","author":"Singh","year":"2024","journal-title":"Appl. Biochem. Biotechnol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1760","DOI":"10.1007\/s00125-024-06198-1","article-title":"The gut microbiota and diabetes: Research, translation, and clinical applications\u20132023 Diabetes, Diabetes Care, and Diabetologia Expert Forum","volume":"67","author":"Byndloss","year":"2024","journal-title":"Diabetologia"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Bertorello, S., Cei, F., Fink, D., Niccolai, E., and Amedei, A. (2024). The Future Exploring of Gut Microbiome-Immunity Interactions: From In Vivo\/Vitro Models to In Silico Innovations. Microorganisms, 12.","DOI":"10.3390\/microorganisms12091828"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1038\/s41574-019-0156-z","article-title":"Gut microbial metabolites in obesity, NAFLD and T2DM","volume":"15","author":"Canfora","year":"2019","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"101772","DOI":"10.1016\/j.molmet.2023.101772","article-title":"EndoC-\u03b2H5 cells are storable and ready-to-use human pancreatic beta cells with physiological insulin secretion","volume":"76","author":"Blanchi","year":"2023","journal-title":"Mol. Metab."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Fr\u00f8rup, C., Gerwig, R., Svane, C.A.S., Mendes Lopes de Melo, J., Henriksen, K., Fl\u00f8yel, T., Pociot, F., Kaur, S., and St\u00f8rling, J. (2023). Characterization of the functional and transcriptomic effects of pro-inflammatory cytokines on human EndoC-\u03b2H5 beta cells. Front. Endocrinol., 14.","DOI":"10.3389\/fendo.2023.1128523"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"6610007","DOI":"10.1155\/2023\/6610007","article-title":"Renewable Human Cell Model for Type 1 Diabetes Research: EndoC-\u03b2H5\/HUVEC Coculture Spheroids","volume":"2023","author":"Porter","year":"2023","journal-title":"J. Diabetes Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1038\/s41589-024-01822-y","article-title":"Mechanistic insights and approaches for beta cell regeneration","volume":"21","author":"Karampelias","year":"2025","journal-title":"Nat. Chem. Biol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1126\/science.1104343","article-title":"Mitochondrial dysfunction and type 2 diabetes","volume":"307","author":"Lowell","year":"2005","journal-title":"Science"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"19453","DOI":"10.1038\/s41598-024-81023-8","article-title":"Enhanced combined in the mulberry juice\u2019s antioxidant activity by using lactic acid bacteria co-culture fermentation","volume":"15","author":"Yaqoob","year":"2025","journal-title":"Sci. Rep."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"14620","DOI":"10.1038\/s41598-017-14815-w","article-title":"Functional coupling of human pancreatic islets and liver spheroids on-a-chip: Towards a novel human ex vivo type 2 diabetes model","volume":"7","author":"Bauer","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"12977","DOI":"10.1038\/ncomms12977","article-title":"Differential hepatic distribution of insulin receptor substrates causes selective insulin resistance in diabetes and obesity","volume":"7","author":"Kubota","year":"2016","journal-title":"Nat. Commun."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"2565","DOI":"10.1007\/s00125-012-2644-8","article-title":"Regulation of insulin sensitivity by serine\/threonine phosphorylation of insulin receptor substrate proteins IRS1 and IRS2","volume":"55","author":"Copps","year":"2012","journal-title":"Diabetologia"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"364","DOI":"10.2337\/db11-1019","article-title":"Short-chain fatty acids stimulate glucagon-like peptide-1 secretion via the G-protein-coupled receptor FFAR2","volume":"61","author":"Tolhurst","year":"2012","journal-title":"Diabetes"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1483","DOI":"10.7150\/ijbs.27173","article-title":"The PI3K\/AKT pathway in obesity and type 2 diabetes","volume":"14","author":"Huang","year":"2018","journal-title":"Int. J. Biol. Sci."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Lee, J., Noh, S., Lim, S., and Kim, B. (2021). Plant Extracts for Type 2 Diabetes: From Traditional Medicine to Modern Drug Discovery. Antioxidants, 10.","DOI":"10.3390\/antiox10010081"},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Abu Shelbayeh, O., Arroum, T., Morris, S., and Busch, K.B. (2023). PGC-1\u03b1 Is a Master Regulator of Mitochondrial Lifecycle and ROS Stress Response. Antioxidants, 12.","DOI":"10.3390\/antiox12051075"},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"M\u00fcnte, E., and Hartmann, P. (2025). The Role of Short-Chain Fatty Acids in Metabolic Dysfunction-Associated Steatotic Liver Disease and Other Metabolic Diseases. Biomolecules, 15.","DOI":"10.3390\/biom15040469"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Ji, T., Li, J., Su, S.L., Zhu, Z.H., Guo, S., Qian, D.W., and Duan, J.A. (2016). Identification and Determination of the Polyhydroxylated Alkaloids Compounds with \u03b1-Glucosidase Inhibitor Activity in Mulberry Leaves of Different Origins. Molecules, 21.","DOI":"10.3390\/molecules21020206"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"17543","DOI":"10.1021\/acs.jafc.3c04022","article-title":"The Chemistry Behind the Folin-Ciocalteu Method for the Estimation of (Poly)phenol Content in Food: Total Phenolic Intake in a Mediterranean Dietary Pattern","volume":"71","year":"2023","journal-title":"J. Agric. Food Chem."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Galla, R., Grisenti, P., Farghali, M., Saccuman, L., Ferraboschi, P., and Uberti, F. (2021). Ovotransferrin Supplementation Improves the Iron Absorption: An In Vitro Gastro-Intestinal Model. Biomedicines, 9.","DOI":"10.3390\/biomedicines9111543"},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Galla, R., Ruga, S., Aprile, S., Ferrari, S., Brovero, A., Grosa, G., Molinari, C., and Uberti, F. (2021). New Hyaluronic Acid from Plant Origin to Improve Joint Protection-An In Vitro Study. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23158114"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"e173214","DOI":"10.1172\/JCI173214","article-title":"SUCNR1 regulates insulin secretion and glucose elevates the succinate response in people with prediabetes","volume":"134","author":"Astiarraga","year":"2024","journal-title":"J. Clin. Investig."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Frigerio, J., Tedesco, E., Benetti, F., Insolia, V., Nicotra, G., Mezzasalma, V., Pagliari, S., Labra, M., and Campone, L. (2021). Anticholesterolemic Activity of Three Vegetal Extracts (Artichoke, Caigua, and Fenugreek) and Their Unique Blend. Front. Pharmacol., 12.","DOI":"10.3389\/fphar.2021.726199"},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Molinari, C., Morsanuto, V., Ruga, S., Notte, F., Farghali, M., Galla, R., and Uberti, F. (2020). The Role of BDNF on Aging-Modulation Markers. Brain Sci., 10.","DOI":"10.3390\/brainsci10050285"},{"key":"ref_61","first-page":"62","article-title":"The assessment of intestinal absorption in vitro","volume":"17","author":"Ceriotti","year":"2014","journal-title":"L\u2019integratore Nutr."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1345","DOI":"10.1007\/s00394-014-0815-8","article-title":"Iron bioavailability from commercially available iron supplements","volume":"54","author":"Christides","year":"2015","journal-title":"Eur. J. Nutr."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Uberti, F., Morsanuto, V., Ghirlanda, S., and Molinari, C. (2017). Iron Absorption from Three Commercially Available Supplements in Gastrointestinal Cell Lines. Nutrients, 9.","DOI":"10.3390\/nu9091008"},{"key":"ref_64","unstructured":"(2025, May 23). Fda.Gov, Available online: https:\/\/www.fda.gov\/media\/117974\/download."},{"key":"ref_65","unstructured":"(2025, May 23). Ema.Eu. Available online: https:\/\/www.ema.europa.eu\/en\/documents\/scientific-guideline\/ich-m9-biopharmaceutics-classification-system-based-biowaivers-step-2b-first-version_en.pdf."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Guha, S., Alvarez, S., and Majumder, K. (2021). Transport of Dietary Anti-Inflammatory Peptide, \u03b3-Glutamyl Valine (\u03b3-EV), across the Intestinal Caco-2 Monolayer. Nutrients, 13.","DOI":"10.3390\/nu13051448"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"e2103495","DOI":"10.1002\/advs.202103495","article-title":"Microengineered Multi-Organoid System from hiPSCs to Recapitulate Human Liver-Islet Axis in Normal and Type 2 Diabetes","volume":"9","author":"Tao","year":"2022","journal-title":"Adv. Sci."},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Ruga, S., Galla, R., Penna, C., Molinari, C., and Uberti, F. (2022). The Activity of Ten Natural Extracts Combined in a Unique Blend to Maintain Cholesterol Homeostasis\u2014In Vitro Model. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23073805"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"532","DOI":"10.1016\/j.jtcme.2021.05.003","article-title":"Preventing c2c12 muscular cells damage combining magnesium and potassium with vitamin D3 and curcumin","volume":"11","author":"Molinari","year":"2021","journal-title":"J. Tradit. Complement. Med."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"10887","DOI":"10.1038\/s41598-020-67843-4","article-title":"The colonic mucosa-associated microbiome in SIV infection: Shift towards bacteroidetes coincides with mucosal CD4+ T cell depletion and enterocyte damage","volume":"10","author":"Allers","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"24234","DOI":"10.1039\/D0RA03517C","article-title":"studies of adhesion properties of six lactic acid bacteria isolated from the longevous population of China","volume":"10","author":"Guan","year":"2020","journal-title":"RSC Adv."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1151","DOI":"10.1007\/s40200-024-01402-w","article-title":"Association of CIITA (rs8048002) and CLEC2D (rs2114870) gene variants and type 1 diabetes mellitus","volume":"23","author":"Saad","year":"2024","journal-title":"J. Diabetes Metab. Disord."},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Wang, Y., Wu, Y., Xu, H., Mei, X., Yu, D., and Li, W. (2017). Antioxidant Properties of Probiotic Bacteria. Nutrients, 9.","DOI":"10.3390\/nu9050521"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/5\/2375\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T05:29:08Z","timestamp":1772774948000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/5\/2375"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,4]]},"references-count":73,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2026,3]]}},"alternative-id":["ijms27052375"],"URL":"https:\/\/doi.org\/10.3390\/ijms27052375","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,4]]}}}