{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T02:27:20Z","timestamp":1793672840403,"version":"4.5.1"},"reference-count":93,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,7,11]],"date-time":"2026-07-11T00:00:00Z","timestamp":1783728000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T00:00:00Z","timestamp":1793664000000},"content-version":"vor","delay-in-days":115,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"name":"Funds from Ludong University","id":[{"id":"https:\/\/ror.org\/028h95t32","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["npj Sci Food"],"DOI":"10.1038\/s41538-026-00986-2","type":"journal-article","created":{"date-parts":[[2026,7,11]],"date-time":"2026-07-11T04:04:45Z","timestamp":1783742685000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Advances in synbiotics and synbiotic functional foods in type 2 diabetes mellitus treatment"],"prefix":"10.1038","volume":"10","author":[{"given":"An-Yu","family":"Zhu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Meng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong-Fang","family":"Ji","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liang","family":"Shen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,7,11]]},"reference":[{"key":"986_CR1","doi-asserted-by":"publisher","unstructured":"Global, regional, and national burden of diabetes from 1990 to 2021, with projections of prevalence to 2050: a systematic analysis for the Global Burden of Disease Study 2021. Lancet 402, 203\u2013234 https:\/\/doi.org\/10.1016\/s0140-6736(23)01301-6 (2023).","DOI":"10.1016\/s0140-6736(23)01301-6"},{"key":"986_CR2","doi-asserted-by":"publisher","first-page":"e002122","DOI":"10.1136\/bmjdrc-2021-002122","volume":"9","author":"T T\u00f6nnies","year":"2021","unstructured":"T\u00f6nnies, T., Rathmann, W., Hoyer, A., Brinks, R. & Kuss, O. Quantifying the underestimation of projected global diabetes prevalence by the International Diabetes Federation (IDF) Diabetes Atlas. BMJ Open Diabetes Res. Care 9, e002122 (2021).","journal-title":"BMJ Open Diabetes Res. Care"},{"key":"986_CR3","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1007\/s40257-018-0400-7","volume":"20","author":"PM Jedlowski","year":"2019","unstructured":"Jedlowski, P. M., Te, C. H., Segal, R. J. & Fazel, M. T. Cutaneous adverse effects of diabetes mellitus medications and medical devices: a review. Am. J. Clin. Dermatol. 20, 97\u2013114 (2019).","journal-title":"Am. J. Clin. Dermatol."},{"key":"986_CR4","doi-asserted-by":"publisher","first-page":"1168","DOI":"10.2337\/db18-1168-P","volume":"67","author":"SM Patel","year":"2018","unstructured":"Patel, S. M. et al. Assessment of adverse renal effects in patients with Type 2 Diabetes Mellitus (T2DM) Receiving Ertugliflozin. Diabetes 67, 1168\u2013116 (2018).","journal-title":"Diabetes"},{"key":"986_CR5","doi-asserted-by":"publisher","DOI":"10.1042\/BSR20182371","volume":"39","author":"H Jiang","year":"2019","unstructured":"Jiang, H. & Zheng, H. Efficacy and adverse reaction to different doses of atorvastatin in the treatment of type II diabetes mellitus. Biosci. Rep. 39, BSR20182371 (2019).","journal-title":"Biosci. Rep."},{"key":"986_CR6","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1038\/nature11450","volume":"490","author":"J Qin","year":"2012","unstructured":"Qin, J. et al. A metagenome-wide association study of gut microbiota in type 2 diabetes. Nature 490, 55\u201360 (2012).","journal-title":"Nature"},{"key":"986_CR7","doi-asserted-by":"publisher","DOI":"10.1016\/j.drudis.2023.103558","volume":"28","author":"AK Sharma","year":"2023","unstructured":"Sharma, A. K. et al. Dysbiosis versus diabesity: Pathological signaling and promising therapeutic strategies. Drug Discovery Today 28, 103558 (2023).","journal-title":"Drug Discovery Today"},{"key":"986_CR8","doi-asserted-by":"publisher","first-page":"389","DOI":"10.1038\/s41586-023-06466-x","volume":"621","author":"T Takeuchi","year":"2023","unstructured":"Takeuchi, T. et al. Gut microbial carbohydrate metabolism contributes to insulin resistance. Nature 621, 389\u2013395 (2023).","journal-title":"Nature"},{"key":"986_CR9","doi-asserted-by":"publisher","first-page":"850","DOI":"10.1038\/nm.4345","volume":"23","author":"H Wu","year":"2017","unstructured":"Wu, H. et al. Metformin alters the gut microbiome of individuals with treatment-naive type 2 diabetes, contributing to the therapeutic effects of the drug. Nat. Med. 23, 850\u2013858 (2017).","journal-title":"Nat. Med."},{"key":"986_CR10","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-36079-x","volume":"14","author":"WL Sun","year":"2023","unstructured":"Sun, W. L. et al. Microbially produced vitamin B12 contributes to the lipid-lowering effect of silymarin. Nat. Commun. 14, 477 (2023).","journal-title":"Nat. Commun."},{"key":"986_CR11","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1016\/j.tips.2015.11.010","volume":"37","author":"L Shen","year":"2016","unstructured":"Shen, L. & Ji, H.-F. Intestinal microbiota and metabolic diseases: pharmacological implications. Trends Pharmacol. Sci. 37, 169\u2013171 (2016).","journal-title":"Trends Pharmacol. Sci."},{"key":"986_CR12","doi-asserted-by":"publisher","first-page":"253","DOI":"10.1080\/19490976.2020.1717719","volume":"11","author":"A Adeshirlarijaney","year":"2020","unstructured":"Adeshirlarijaney, A. & Gewirtz, A. T. Considering gut microbiota in treatment of type 2 diabetes mellitus. Gut Microbes 11, 253\u2013264 (2020).","journal-title":"Gut Microbes"},{"key":"986_CR13","doi-asserted-by":"publisher","first-page":"242","DOI":"10.1038\/nature11552","volume":"489","author":"V Tremaroli","year":"2012","unstructured":"Tremaroli, V. & B\u00e4ckhed, F. Functional interactions between the gut microbiota and host metabolism. Nature 489, 242\u2013249 (2012).","journal-title":"Nature"},{"key":"986_CR14","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2021.632335","volume":"12","author":"MN Huda","year":"2021","unstructured":"Huda, M. N., Kim, M. & Bennett, B. J. Modulating the microbiota as a therapeutic intervention for type 2 diabetes. Front. Endocrinol. 12, 632335 (2021).","journal-title":"Front. Endocrinol."},{"key":"986_CR15","doi-asserted-by":"publisher","first-page":"1455","DOI":"10.3390\/foods10071455","volume":"10","author":"P Toejing","year":"2021","unstructured":"Toejing, P., Khampithum, N., Sirilun, S., Chaiyasut, C. & Lailerd, N. Influence of Lactobacillus paracasei HII01 Supplementation on Glycemia and Inflammatory Biomarkers in Type 2 Diabetes: A Randomized Clinical Trial. Foods 10, 1455 (2021).","journal-title":"Foods"},{"key":"986_CR16","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-35014-1","volume":"8","author":"MC Hsieh","year":"2018","unstructured":"Hsieh, M. C. et al. The beneficial effects of Lactobacillus reuteri ADR-1 or ADR-3 consumption on type 2 diabetes mellitus: a randomized, double-blinded, placebo-controlled trial. Sci. Rep. 8, 16791 (2018).","journal-title":"Sci. Rep."},{"key":"986_CR17","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1016\/j.clnu.2015.11.011","volume":"36","author":"LB Tonucci","year":"2017","unstructured":"Tonucci, L. B., Dos Santos, K. M. O., de Oliveira, L. L., Ribeiro, S. M. R. & Martino, H. S. D. Clinical application of probiotics in type 2 diabetes mellitus: A randomized, double-blind, placebo-controlled study. Clin. Nutr. 36, 85\u201392 (2017).","journal-title":"Clin. Nutr."},{"key":"986_CR18","doi-asserted-by":"publisher","first-page":"234","DOI":"10.1016\/j.diabet.2016.04.009","volume":"42","author":"M Karamali","year":"2016","unstructured":"Karamali, M. et al. Effects of probiotic supplementation on glycaemic control and lipid profiles in gestational diabetes: A randomized, double-blind, placebo-controlled trial. Diabetes Metab 42, 234\u2013241 (2016).","journal-title":"Diabetes Metab"},{"key":"986_CR19","doi-asserted-by":"publisher","first-page":"3447","DOI":"10.3390\/nu16203447","volume":"16","author":"OC Iatcu","year":"2024","unstructured":"Iatcu, O. C., Hamamah, S. & Covasa, M. Harnessing Prebiotics to Improve Type 2 Diabetes Outcomes. Nutrients 16, 3447 (2024).","journal-title":"Nutrients"},{"key":"986_CR20","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1016\/j.foodres.2018.07.013","volume":"113","author":"GTC Delgado","year":"2018","unstructured":"Delgado, G. T. C. & Tamashiro, W. M.dS. C. Role of prebiotics in regulation of microbiota and prevention of obesity. Food Res. Int. 113, 183\u2013188 (2018).","journal-title":"Food Res. Int."},{"key":"986_CR21","doi-asserted-by":"publisher","first-page":"6097","DOI":"10.3390\/ijms23116097","volume":"23","author":"A Megur","year":"2022","unstructured":"Megur, A., Daliri, E. B., Baltriukien\u0117, D. & Burokas, A. Prebiotics as a Tool for the Prevention and Treatment of Obesity and Diabetes: Classification and Ability to Modulate the Gut Microbiota. Int. J. Mol. Sci. 23, 6097 (2022).","journal-title":"Int. J. Mol. Sci."},{"key":"986_CR22","doi-asserted-by":"publisher","first-page":"5925","DOI":"10.1039\/D1FO04428A","volume":"13","author":"N Pengrattanachot","year":"2022","unstructured":"Pengrattanachot, N., Thongnak, L. & Lungkaphin, A. The impact of prebiotic fructooligosaccharides on gut dysbiosis and inflammation in obesity and diabetes related kidney disease. Food Funct 13, 5925\u20135945 (2022).","journal-title":"Food Funct"},{"key":"986_CR23","doi-asserted-by":"publisher","first-page":"264","DOI":"10.2337\/db18-264-LB","volume":"67","author":"S Ahmadi","year":"2018","unstructured":"Ahmadi, S., Nagpal, R. K., Wang, S. & Yadav, H. New prebiotics to ameliorate high-fat diet-induced obesity and diabetes via modulation of microbiome-gut-brain axis. Diabetes 67, 264\u20132 (2018).","journal-title":"Diabetes"},{"key":"986_CR24","doi-asserted-by":"publisher","first-page":"216","DOI":"10.3389\/fphys.2015.00216","volume":"6","author":"J Yang","year":"2015","unstructured":"Yang, J. et al. Xylooligosaccharide supplementation alters gut bacteria in both healthy and prediabetic adults: a pilot study. Front. Physiol. 6, 216 (2015).","journal-title":"Front. Physiol."},{"key":"986_CR25","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1053\/j.gastro.2017.03.051","volume":"153","author":"EE Canfora","year":"2017","unstructured":"Canfora, E. E. et al. Supplementation of Diet With Galacto-oligosaccharides Increases Bifidobacteria, but Not Insulin Sensitivity, in Obese Prediabetic Individuals. Gastroenterol 153, 87\u201397.e83 (2017).","journal-title":"Gastroenterol"},{"key":"986_CR26","doi-asserted-by":"publisher","unstructured":"Hosseini, E., Mokhtari, Z. & Askari, G. Effect of Prebiotic Supplementation on Health Status in Adults with Prediabetes: A Systematic Review and Meta-Analysis of Randomized Clinical Trials. J. Nutr. https:\/\/doi.org\/10.1016\/j.tjnut.2025.01.003 (2025).","DOI":"10.1016\/j.tjnut.2025.01.003"},{"key":"986_CR27","doi-asserted-by":"publisher","first-page":"793","DOI":"10.3390\/nu10060793","volume":"10","author":"ME Baugh","year":"2018","unstructured":"Baugh, M. E. et al. Inulin Supplementation Does Not Reduce Plasma Trimethylamine N-Oxide Concentrations in Individuals at Risk for Type 2 Diabetes. Nutrients 10, 793 (2018).","journal-title":"Nutrients"},{"key":"986_CR28","doi-asserted-by":"publisher","first-page":"S108","DOI":"10.1093\/cid\/civ177","volume":"60","author":"R Patel","year":"2015","unstructured":"Patel, R. & DuPont, H. L. New approaches for bacteriotherapy: prebiotics, new-generation probiotics, and synbiotics. Clin. Infect. Dis. 60, S108\u2013S121 (2015).","journal-title":"Clin. Infect. Dis."},{"key":"986_CR29","doi-asserted-by":"publisher","DOI":"10.1016\/j.micres.2025.128174","volume":"297","author":"Y Zhan","year":"2025","unstructured":"Zhan, Y. et al. Synergistic action of non-digestible xylooligosaccharide and Lactiplantibacillus plantarum ZDY2013 against high fat diet and streptozocin-induced type 2 diabetes mellitus in rats. Microbiol. Res. 297, 128174 (2025).","journal-title":"Microbiol. Res."},{"key":"986_CR30","doi-asserted-by":"publisher","unstructured":"Wang, J., et al. Beyond conventional therapies: Gut microbiota modulation and macromolecular drugs in the battle against cardiometabolic diseases. J. Pharm. Anal. 101416 https:\/\/doi.org\/10.1016\/j.jpha.2025.101416 (2025).","DOI":"10.1016\/j.jpha.2025.101416"},{"key":"986_CR31","doi-asserted-by":"publisher","first-page":"19442","DOI":"10.1021\/acs.jafc.5c03515","volume":"73","author":"M Li","year":"2025","unstructured":"Li, M. et al. Synbiotic Intervention with Inulin and Lactiplantibacillus plantarum LPm77 Attenuates Type 2 Diabetes via Enhanced TUDCA Metabolism and Gut-Liver Axis Modulation. J. Agric. Food Chem. 73, 19442\u201319459 (2025).","journal-title":"J. Agric. Food Chem."},{"key":"986_CR32","doi-asserted-by":"publisher","unstructured":"Setayesh, A., et al. Probiotics and Synbiotics Supplementation Reduce Inflammatory Cytokines in Individuals with Prediabetes and Type 2 Diabetes Mellitus: Findings from a Systematic Review Meta-analysis. Adv. Nutr. 100526 https:\/\/doi.org\/10.1016\/j.advnut.2025.100526 (2025).","DOI":"10.1016\/j.advnut.2025.100526"},{"key":"986_CR33","doi-asserted-by":"publisher","DOI":"10.1016\/j.fbio.2024.105747","volume":"63","author":"S Kiran","year":"2025","unstructured":"Kiran, S., Sreeja, V. & Patel, H. K. In vitro probiotic and bio-functional properties of a synbiotic composed of Lactobacillus helveticus MTCC 5463 and Fructo-oligosaccharide. Food Biosci 63, 105747 (2025).","journal-title":"Food Biosci"},{"key":"986_CR34","doi-asserted-by":"publisher","first-page":"303","DOI":"10.1016\/j.phrs.2019.02.016","volume":"142","author":"HJ Zheng","year":"2019","unstructured":"Zheng, H. J. et al. The effect of probiotic and synbiotic supplementation on biomarkers of inflammation and oxidative stress in diabetic patients: A systematic review and meta-analysis of randomized controlled trials. Pharmacol. Res. 142, 303\u2013313 (2019).","journal-title":"Pharmacol. Res."},{"key":"986_CR35","doi-asserted-by":"publisher","DOI":"10.1016\/j.foodres.2021.110208","volume":"142","author":"A Zepeda-Hern\u00e1ndez","year":"2021","unstructured":"Zepeda-Hern\u00e1ndez, A., Garcia-Amezquita, L. E., Requena, T. & Garc\u00eda-Cayuela, T. Probiotics, prebiotics, and synbiotics added to dairy products: Uses and applications to manage type 2 diabetes. Food Res. Int. 142, 110208 (2021).","journal-title":"Food Res. Int."},{"key":"986_CR36","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2024.107483","volume":"210","author":"K Chen","year":"2024","unstructured":"Chen, K. et al. Targeting gut microbiota as a therapeutic target in T2DM: A review of multi-target interactions of probiotics, prebiotics, postbiotics, and synbiotics with the intestinal barrier. Pharmacol. Res. 210, 107483 (2024).","journal-title":"Pharmacol. Res."},{"key":"986_CR37","doi-asserted-by":"publisher","first-page":"2991","DOI":"10.1016\/j.dsx.2018.07.016","volume":"13","author":"N Kassaian","year":"2019","unstructured":"Kassaian, N., Feizi, A., Aminorroaya, A. & Amini, M. Probiotic and synbiotic supplementation could improve metabolic syndrome in prediabetic adults: A randomized controlled trial. Diabetes Metab. Syndr.: Clin. Res. Rev. 13, 2991\u20132996 (2019).","journal-title":"Diabetes Metab. Syndr.: Clin. Res. Rev."},{"key":"986_CR38","doi-asserted-by":"publisher","DOI":"10.1016\/j.nut.2020.110854","volume":"79-80","author":"N Kassaian","year":"2020","unstructured":"Kassaian, N. et al. The effects of 6 mo of supplementation with probiotics and synbiotics on gut microbiota in the adults with prediabetes: A double blind randomized clinical trial. Nutrition 79-80, 110854 (2020).","journal-title":"Nutrition"},{"key":"986_CR39","doi-asserted-by":"publisher","DOI":"10.3389\/fnut.2022.1001419","volume":"9","author":"A Kordowski","year":"2022","unstructured":"Kordowski, A. et al. A nutritional supplement based on a synbiotic combination of Bacillus subtilis DSM 32315 and L-alanyl-L-glutamine improves glucose metabolism in healthy prediabetic subjects - A real-life post-marketing study. Front. Nutr. 9, 1001419 (2022).","journal-title":"Front. Nutr."},{"key":"986_CR40","first-page":"1239","volume":"5","author":"S Mahboobi","year":"2014","unstructured":"Mahboobi, S. et al. The effects of probiotic supplementation on markers of blood lipids, and blood pressure in patients with prediabetes: a randomized clinical trial. Int. J. Prev. Med. 5, 1239\u20131246 (2014).","journal-title":"Int. J. Prev. Med."},{"key":"986_CR41","doi-asserted-by":"publisher","first-page":"558","DOI":"10.3390\/nu13020558","volume":"13","author":"A Kanazawa","year":"2021","unstructured":"Kanazawa, A. et al. Effects of Synbiotic Supplementation on Chronic Inflammation and the Gut Microbiota in Obese Patients with Type 2 Diabetes Mellitus: A Randomized Controlled Study. Nutrients 13, 558 (2021).","journal-title":"Nutrients"},{"key":"986_CR42","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-18414-8","volume":"11","author":"Y Zhang","year":"2020","unstructured":"Zhang, Y. et al. Gut microbiome-related effects of berberine and probiotics on type 2 diabetes (the PREMOTE study). Nat. Commun. 11, 5015 (2020).","journal-title":"Nat. Commun."},{"key":"986_CR43","doi-asserted-by":"publisher","first-page":"e001319","DOI":"10.1136\/bmjdrc-2020-001319","volume":"8","author":"F Perraudeau","year":"2020","unstructured":"Perraudeau, F. et al. Improvements to postprandial glucose control in subjects with type 2 diabetes: a multicenter, double blind, randomized placebo-controlled trial of a novel probiotic formulation. BMJ Open Diabetes Res. Care 8, e001319 (2020).","journal-title":"BMJ Open Diabetes Res. Care"},{"key":"986_CR44","doi-asserted-by":"publisher","first-page":"1248","DOI":"10.1007\/s12602-018-9499-3","volume":"11","author":"A Soleimani","year":"2019","unstructured":"Soleimani, A. et al. The Effects of Synbiotic Supplementation on Metabolic Status in Diabetic Patients Undergoing Hemodialysis: a Randomized, Double-Blinded, Placebo-Controlled Trial. Probiotics Antimicrob. Proteins 11, 1248\u20131256 (2019).","journal-title":"Probiotics Antimicrob. Proteins"},{"key":"986_CR45","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1055\/s-0042-105441","volume":"125","author":"M Tajabadi-Ebrahimi","year":"2017","unstructured":"Tajabadi-Ebrahimi, M. et al. A Randomized Controlled Clinical Trial Investigating the Effect of Synbiotic Administration on Markers of Insulin Metabolism and Lipid Profiles in Overweight Type 2 Diabetic Patients with Coronary Heart Disease. Exp. Clin. Endocrinol. Diabetes 125, 21\u201327 (2017).","journal-title":"Exp. Clin. Endocrinol. Diabetes"},{"key":"986_CR46","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1007\/s12602-017-9343-1","volume":"11","author":"A Farrokhian","year":"2019","unstructured":"Farrokhian, A. et al. The Effects of Synbiotic Supplementation on Carotid Intima-Media Thickness, Biomarkers of Inflammation, and Oxidative Stress in People with Overweight, Diabetes, and Coronary Heart Disease: a Randomized, Double-Blind, Placebo-Controlled Trial. Probiotics Antimicrob. Proteins 11, 133\u2013142 (2019).","journal-title":"Probiotics Antimicrob. Proteins"},{"key":"986_CR47","doi-asserted-by":"publisher","first-page":"e0225168","DOI":"10.1371\/journal.pone.0225168","volume":"14","author":"RS Madempudi","year":"2019","unstructured":"Madempudi, R. S., Ahire, J. J., Neelamraju, J., Tripathi, A. & Nanal, S. Efficacy of UB0316, a multi-strain probiotic formulation in patients with type 2 diabetes mellitus: A double blind, randomized, placebo controlled study. PLoS One 14, e0225168 (2019).","journal-title":"PLoS One"},{"key":"986_CR48","doi-asserted-by":"publisher","DOI":"10.1186\/s13063-020-04236-y","volume":"21","author":"F Zeinali","year":"2020","unstructured":"Zeinali, F. et al. Effects of synbiotic supplementation on gut microbiome, serum level of TNF-\u03b1, and expression of microRNA-126 and microRNA-146a in patients with type 2 diabetes mellitus: study protocol for a double-blind controlled randomized clinical trial. Trials 21, 324 (2020).","journal-title":"Trials"},{"key":"986_CR49","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1186\/s40200-017-0304-8","volume":"16","author":"ZS Ebrahimi","year":"2017","unstructured":"Ebrahimi, Z. S., Nasli-Esfahani, E., Nadjarzade, A. & Mozaffari-Khosravi, H. Effect of symbiotic supplementation on glycemic control, lipid profiles and microalbuminuria in patients with non-obese type 2 diabetes: a randomized, double-blind, clinical trial. J. Diabetes Metab. Disord. 16, 23 (2017).","journal-title":"J. Diabetes Metab. Disord."},{"key":"986_CR50","doi-asserted-by":"publisher","DOI":"10.1016\/j.fbio.2024.104948","volume":"61","author":"C Li","year":"2024","unstructured":"Li, C. et al. Synbiotic supplementation with xylooligosaccharide derived probiotic Lactobacillus gasseri and prebiotic mixture exerts antidiabetic effects via collaborative action. Food Biosci 61, 104948 (2024).","journal-title":"Food Biosci"},{"key":"986_CR51","doi-asserted-by":"publisher","first-page":"6385","DOI":"10.1039\/D3FO00162H","volume":"14","author":"M Cui","year":"2023","unstructured":"Cui, M. et al. Dose-dependent effects of xylooligosaccharides on glycemic regulation with L. rhamnosus CCFM1060 in diabetic mice. Food Funct 14, 6385\u20136396 (2023).","journal-title":"Food Funct"},{"key":"986_CR52","doi-asserted-by":"publisher","DOI":"10.1186\/s12967-019-02169-y","volume":"18","author":"M Morshedi","year":"2020","unstructured":"Morshedi, M., Saghafi-Asl, M. & Hosseinifard, E. S. The potential therapeutic effects of the gut microbiome manipulation by synbiotic containing-Lactobacillus plantarum on neuropsychological performance of diabetic rats. J. Transl. Med. 18, 18 (2020).","journal-title":"J. Transl. Med."},{"key":"986_CR53","doi-asserted-by":"publisher","DOI":"10.1155\/2020\/4745389","volume":"2020","author":"S Sefidgari-Abrasi","year":"2020","unstructured":"Sefidgari-Abrasi, S. et al. Lactobacillus plantarum And Inulin: Therapeutic Agents to Enhance Cardiac Ob Receptor Expression and Suppress Cardiac Apoptosis in Type 2 Diabetic Rats. J. Diabetes Res. 2020, 4745389 (2020).","journal-title":"J. Diabetes Res."},{"key":"986_CR54","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2023.1158652","volume":"14","author":"F Meng","year":"2023","unstructured":"Meng, F. et al. Effects of the synbiotic composed of mangiferin and Lactobacillus reuteri 1-12 on type 2 diabetes mellitus rats. Front. Microbiol. 14, 1158652 (2023).","journal-title":"Front. Microbiol."},{"key":"986_CR55","doi-asserted-by":"publisher","unstructured":"Elebeedy, D., et al. Synergistic Effects of Lactobacillus acidophilus and Balanites aegyptiaca in Managing Hyperglycemia, Oxidative Stress, and Inflammation in Diabetic Rats. Curr. Pharm. Biotechnol. https:\/\/doi.org\/10.2174\/0113892010362400250121075011 (2025).","DOI":"10.2174\/0113892010362400250121075011"},{"key":"986_CR56","doi-asserted-by":"publisher","first-page":"319","DOI":"10.1089\/jmf.2020.4759","volume":"24","author":"L Yu","year":"2021","unstructured":"Yu, L. et al. Synergistic Protective Effects of Different Dietary Supplements Against Type 2 Diabetes via Regulating Gut Microbiota. J. Med. Food 24, 319\u2013330 (2021).","journal-title":"J. Med. Food"},{"key":"986_CR57","doi-asserted-by":"publisher","first-page":"3161","DOI":"10.3390\/nu13093161","volume":"13","author":"WC Chiou","year":"2021","unstructured":"Chiou, W. C. et al. Synbiotic Intervention with an Adlay-Based Prebiotic and Probiotics Improved Diet-Induced Metabolic Disturbance in Mice by Modulation of the Gut Microbiota. Nutrients 13, 3161 (2021).","journal-title":"Nutrients"},{"key":"986_CR58","doi-asserted-by":"publisher","first-page":"114","DOI":"10.1186\/1476-511X-11-114","volume":"11","author":"MN Roselino","year":"2012","unstructured":"Roselino, M. N. et al. A potential synbiotic product improves the lipid profile of diabetic rats. Lipids Health Dis 11, 114 (2012).","journal-title":"Lipids Health Dis"},{"key":"986_CR59","doi-asserted-by":"publisher","first-page":"441","DOI":"10.1080\/21691401.2018.1458731","volume":"46","author":"S Westfall","year":"2018","unstructured":"Westfall, S., Lomis, N. & Prakash, S. A novel polyphenolic prebiotic and probiotic formulation have synergistic effects on the gut microbiota influencing Drosophila melanogaster physiology. Artif. Cells Nanomed. Biotechnol. 46, 441\u2013455 (2018).","journal-title":"Artif. Cells Nanomed. Biotechnol."},{"key":"986_CR60","doi-asserted-by":"publisher","first-page":"374","DOI":"10.1016\/j.jff.2018.07.012","volume":"48","author":"S Westfall","year":"2018","unstructured":"Westfall, S., Lomis, N. & Prakash, S. A polyphenol-rich prebiotic in combination with a novel probiotic formulation alleviates markers of obesity and diabetes in Drosophila. J. Funct. Foods 48, 374\u2013386 (2018).","journal-title":"J. Funct. Foods"},{"key":"986_CR61","doi-asserted-by":"publisher","first-page":"884","DOI":"10.1007\/s12602-022-09962-0","volume":"14","author":"A Bhanja","year":"2022","unstructured":"Bhanja, A., Nayak, N., Mukherjee, S., Sutar, P. P. & Mishra, M. Treating the Onset of Diabetes Using Probiotics Along with Prebiotic from Pachyrhizus erosus in High-Fat Diet Fed Drosophila melanogaster. Probiotics Antimicrob. Proteins 14, 884\u2013903 (2022).","journal-title":"Probiotics Antimicrob. Proteins"},{"key":"986_CR62","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1186\/s13098-015-0075-7","volume":"7","author":"LK Stenman","year":"2015","unstructured":"Stenman, L. K. et al. Probiotic B420 and prebiotic polydextrose improve efficacy of antidiabetic drugs in mice. Diabetol. Metab. Syndr. 7, 75 (2015).","journal-title":"Diabetol. Metab. Syndr."},{"key":"986_CR63","doi-asserted-by":"publisher","first-page":"2117","DOI":"10.1007\/s00125-023-05981-w","volume":"66","author":"D Yavorov-Dayliev","year":"2023","unstructured":"Yavorov-Dayliev, D. et al. Glucose-lowering effects of a synbiotic combination containing Pediococcus acidilactici in C. elegans and mice. Diabetologia 66, 2117\u20132138 (2023).","journal-title":"Diabetologia"},{"key":"986_CR64","doi-asserted-by":"publisher","first-page":"3801","DOI":"10.1021\/acs.jafc.7b00233","volume":"65","author":"X Li","year":"2017","unstructured":"Li, X., Sui, Y., Wu, Q., Xie, B. & Sun, Z. Attenuated mTOR Signaling and Enhanced Glucose Homeostasis by Dietary Supplementation with Lotus Seedpod Oligomeric Procyanidins in Streptozotocin (STZ)-Induced Diabetic Mice. J. Agric. Food Chem. 65, 3801\u20133810 (2017).","journal-title":"J. Agric. Food Chem."},{"key":"986_CR65","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s13197-022-05621-y","volume":"61","author":"M Yadav","year":"2024","unstructured":"Yadav, M. et al. Synbiotics as potent functional food: recent updates on therapeutic potential and mechanistic insight. J. Food Sci. Technol.-Mys 61, 1\u201315 (2024).","journal-title":"J. Food Sci. Technol.-Mys"},{"key":"986_CR66","doi-asserted-by":"publisher","DOI":"10.3389\/fnut.2022.957516","volume":"9","author":"NJ Temple","year":"2022","unstructured":"Temple, N. J. A rational definition for functional foods: A perspective. Front. Nutr. 9, 957516 (2022).","journal-title":"Front. Nutr."},{"key":"986_CR67","doi-asserted-by":"publisher","DOI":"10.3389\/fnut.2023.1164676","volume":"10","author":"RB Nambiar","year":"2023","unstructured":"Nambiar, R. B., Perumal, A. B., Shittu, T., Sadiku, E. R. & Sellamuthu, P. S. Editorial: Probiotics, prebiotics, synbiotics, postbiotics, & paraprobiotics - New perspective for functional foods and nutraceuticals. Front. Nutr. 10, 1164676 (2023).","journal-title":"Front. Nutr."},{"key":"986_CR68","doi-asserted-by":"publisher","first-page":"1647","DOI":"10.3390\/ijms22041647","volume":"22","author":"B Miller","year":"2021","unstructured":"Miller, B., Mainali, R., Nagpal, R. & Yadav, H. A Newly Developed Synbiotic Yogurt Prevents Diabetes by Improving the Microbiome-Intestine-Pancreas Axis. Int. J. Mol. Sci. 22, 1647 (2021).","journal-title":"Int. J. Mol. Sci."},{"key":"986_CR69","doi-asserted-by":"publisher","first-page":"7696","DOI":"10.1039\/D0FO01860K","volume":"11","author":"Q Ban","year":"2020","unstructured":"Ban, Q., Cheng, J., Sun, X., Jiang, Y. & Guo, M. Effect of feeding type 2 diabetes mellitus rats with synbiotic yogurt sweetened with monk fruit extract on serum lipid levels and hepatic AMPK (5\u2019 adenosine monophosphate-activated protein kinase) signaling pathway. Food Funct 11, 7696\u20137706 (2020).","journal-title":"Food Funct"},{"key":"986_CR70","doi-asserted-by":"publisher","first-page":"377","DOI":"10.3390\/nu14020377","volume":"14","author":"J Zhao","year":"2022","unstructured":"Zhao, J. et al. A Potential Synbiotic Strategy for the Prevention of Type 2 Diabetes: Lactobacillus paracasei JY062 and Exopolysaccharide Isolated from Lactobacillus plantarum JY039. Nutrients 14, 377 (2022).","journal-title":"Nutrients"},{"key":"986_CR71","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1186\/1476-511X-11-29","volume":"11","author":"C Moroti","year":"2012","unstructured":"Moroti, C., Souza Magri, L. F., de Rezende Costa, M., Cavallini, D. C. & Sivieri, K. Effect of the consumption of a new symbiotic shake on glycemia and cholesterol levels in elderly people with type 2 diabetes mellitus. Lipids Health Dis 11, 29 (2012).","journal-title":"Lipids Health Dis"},{"key":"986_CR72","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1186\/s13098-019-0496-9","volume":"11","author":"A Ghafouri","year":"2019","unstructured":"Ghafouri, A. et al. Effect of synbiotic bread containing lactic acid on glycemic indicators, biomarkers of antioxidant status and inflammation in patients with type 2 diabetes: a randomized controlled trial. Diabetol. Metab. Syndr. 11, 103 (2019).","journal-title":"Diabetol. Metab. Syndr."},{"key":"986_CR73","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1159\/000365153","volume":"65","author":"M Tajadadi-Ebrahimi","year":"2014","unstructured":"Tajadadi-Ebrahimi, M. et al. Effects of daily consumption of synbiotic bread on insulin metabolism and serum high-sensitivity C-reactive protein among diabetic patients: a double-blind, randomized, controlled clinical trial. Ann. Nutr. Metab. 65, 34\u201341 (2014).","journal-title":"Ann. Nutr. Metab."},{"key":"986_CR74","doi-asserted-by":"publisher","first-page":"2969","DOI":"10.1007\/s00394-019-02135-w","volume":"59","author":"A Horvath","year":"2020","unstructured":"Horvath, A. et al. Effects of a multispecies synbiotic on glucose metabolism, lipid marker, gut microbiome composition, gut permeability, and quality of life in diabesity: a randomized, double-blind, placebo-controlled pilot study. Eur. J. Nutr. 59, 2969\u20132983 (2020).","journal-title":"Eur. J. Nutr."},{"key":"986_CR75","doi-asserted-by":"publisher","first-page":"248","DOI":"10.1016\/j.clnu.2024.11.042","volume":"44","author":"C Zhang","year":"2025","unstructured":"Zhang, C. et al. Effects of synbiotics surpass probiotics alone in improving type 2 diabetes mellitus: A randomized, double-blind, placebo-controlled trial. Clin. Nutr. 44, 248\u2013258 (2025).","journal-title":"Clin. Nutr."},{"key":"986_CR76","doi-asserted-by":"publisher","first-page":"198","DOI":"10.1016\/j.clnu.2013.05.015","volume":"33","author":"Z Asemi","year":"2014","unstructured":"Asemi, Z., Khorrami-Rad, A., Alizadeh, S. A., Shakeri, H. & Esmaillzadeh, A. Effects of synbiotic food consumption on metabolic status of diabetic patients: a double-blind randomized cross-over controlled clinical trial. Clin. Nutr. 33, 198\u2013203 (2014).","journal-title":"Clin. Nutr."},{"key":"986_CR77","doi-asserted-by":"publisher","first-page":"819","DOI":"10.1016\/j.clnu.2015.07.009","volume":"35","author":"Z Asemi","year":"2016","unstructured":"Asemi, Z., Alizadeh, S. A., Ahmad, K., Goli, M. & Esmaillzadeh, A. Effects of beta-carotene fortified synbiotic food on metabolic control of patients with type 2 diabetes mellitus: A double-blind randomized cross-over controlled clinical trial. Clin. Nutr. 35, 819\u2013825 (2016).","journal-title":"Clin. Nutr."},{"key":"986_CR78","doi-asserted-by":"publisher","first-page":"43","DOI":"10.4103\/ijpvm.IJPVM_257_16","volume":"8","author":"Z Asemi","year":"2017","unstructured":"Asemi, Z. et al. Effects of Synbiotic Food Consumption on Serum Minerals, Liver Enzymes, and Blood Pressure in Patients with Type 2 Diabetes: A Double-blind Randomized Cross-over Controlled Clinical Trial. Int. J. Prev. Med. 8, 43 (2017).","journal-title":"Int. J. Prev. Med."},{"key":"986_CR79","doi-asserted-by":"publisher","DOI":"10.1016\/j.fbio.2020.100740","volume":"37","author":"C Zhang","year":"2020","unstructured":"Zhang, C. et al. Storage stability and in vitro digestion of microencapsulated powder containing fermented noni juice and probiotics. Food Biosci 37, 100740 (2020).","journal-title":"Food Biosci"},{"key":"986_CR80","doi-asserted-by":"publisher","DOI":"10.1016\/j.foodres.2020.110033","volume":"140","author":"TC Pimentel","year":"2021","unstructured":"Pimentel, T. C., Costa, W., Bar\u00e3o, C. E., Rosset, M. & Magnani, M. Vegan probiotic products: A modern tendency or the newest challenge in functional foods. Food Res. Int. 140, 110033 (2021).","journal-title":"Food Res. Int."},{"key":"986_CR81","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-021-98194-3","volume":"11","author":"A Anand","year":"2021","unstructured":"Anand, A., Yoshida, S. & Aoyagi, H. Author Correction: Tailored synbiotic powder (functional food) to prevent hyperphosphataemia (kidney disorder). Sci. Rep. 11, 18560 (2021).","journal-title":"Sci. Rep."},{"key":"986_CR82","doi-asserted-by":"publisher","first-page":"622","DOI":"10.3390\/fermentation8110622","volume":"8","author":"A Asghar","year":"2022","unstructured":"Asghar, A. et al. Isolation and molecular characterization of processed soybean waste for the development of synbiotic yogurt. Fermentation 8, 622 (2022).","journal-title":"Fermentation"},{"key":"986_CR83","doi-asserted-by":"publisher","unstructured":"Xiong, H.-H. & Xu, Y.-J. The Application and Development of Artificial Intelligence in Functional Food Research. Trends Food Sci. Technol. 105612 https:\/\/doi.org\/10.1016\/j.tifs.2026.105612 (2026).","DOI":"10.1016\/j.tifs.2026.105612"},{"key":"986_CR84","doi-asserted-by":"publisher","first-page":"473","DOI":"10.1016\/S0958-6946(98)00071-5","volume":"8","author":"CJ Ziemer","year":"1998","unstructured":"Ziemer, C. J. & Gibson, G. R. An overview of probiotics, prebiotics and synbiotics in the functional food concept: perspectives and future strategies. Int. Dairy J. 8, 473\u2013479 (1998).","journal-title":"Int. Dairy J."},{"key":"986_CR85","doi-asserted-by":"publisher","first-page":"1021","DOI":"10.1080\/10942912.2024.2380376","volume":"27","author":"M Nuaman","year":"2024","unstructured":"Nuaman, M. et al. Survivability of probiotic under simulated gastrointestinal conditions as affected by synbiotic (alginate-arabinoxylan) encapsulation. Int. J. Food Prop. 27, 1021\u20131032 (2024).","journal-title":"Int. J. Food Prop."},{"key":"986_CR86","doi-asserted-by":"publisher","DOI":"10.1016\/j.foodres.2025.116949","volume":"218","author":"A-Y Zhu","year":"2025","unstructured":"Zhu, A.-Y., Ji, H.-F. & Shen, L. Advances in synthesis of synbiotic microcapsules with oligosaccharides and polysaccharides and their biomedical applications. Food Res. Int. 218, 116949 (2025).","journal-title":"Food Res. Int."},{"key":"986_CR87","doi-asserted-by":"publisher","DOI":"10.1016\/j.cis.2022.102781","volume":"309","author":"Q Gu","year":"2022","unstructured":"Gu, Q. et al. Encapsulation of multiple probiotics, synbiotics, or nutrabiotics for improved health effects: A review. Adv. Colloid Interface Sci. 309, 102781 (2022).","journal-title":"Adv. Colloid Interface Sci."},{"key":"986_CR88","doi-asserted-by":"publisher","unstructured":"Bhutto, R. A., et al. Recent Trends in Co-encapsulation of Probiotics with Prebiotics and their Applications in the Food Industry. Trends Food Sci. Technol. 104829 https:\/\/doi.org\/10.1016\/j.tifs.2024.104829 (2024).","DOI":"10.1016\/j.tifs.2024.104829"},{"key":"986_CR89","doi-asserted-by":"publisher","first-page":"2470","DOI":"10.1080\/10408398.2020.1854169","volume":"62","author":"A Rashidinejad","year":"2022","unstructured":"Rashidinejad, A. et al. Co-encapsulation of probiotics with prebiotics and their application in functional\/synbiotic dairy products. Crit. Rev. Food Sci. Nutr. 62, 2470\u20132494 (2022).","journal-title":"Crit. Rev. Food Sci. Nutr."},{"key":"986_CR90","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1038\/s41387-024-00354-7","volume":"14","author":"MA Zolghadrpour","year":"2024","unstructured":"Zolghadrpour, M. A. et al. The effect of a new developed synbiotic yogurt consumption on metabolic syndrome components in adults with metabolic syndrome: a randomized controlled clinical trial. Nutr. Diabetes 14, 97 (2024).","journal-title":"Nutr. Diabetes"},{"key":"986_CR91","doi-asserted-by":"publisher","first-page":"1394","DOI":"10.1017\/S0007114516003457","volume":"116","author":"S Ahmadi","year":"2016","unstructured":"Ahmadi, S., Jamilian, M., Tajabadi-Ebrahimi, M., Jafari, P. & Asemi, Z. The effects of synbiotic supplementation on markers of insulin metabolism and lipid profiles in gestational diabetes: a randomised, double-blind, placebo-controlled trial. Br. J. Nutr. 116, 1394\u20131401 (2016).","journal-title":"Br. J. Nutr."},{"key":"986_CR92","doi-asserted-by":"publisher","first-page":"496","DOI":"10.1007\/s12602-017-9313-7","volume":"10","author":"M Karamali","year":"2018","unstructured":"Karamali, M. et al. The Effects of Synbiotic Supplementation on Pregnancy Outcomes in Gestational Diabetes. Probiotics Antimicrob. Proteins 10, 496\u2013503 (2018).","journal-title":"Probiotics Antimicrob. Proteins"},{"key":"986_CR93","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1016\/j.diabres.2018.02.008","volume":"138","author":"Z Nabhani","year":"2018","unstructured":"Nabhani, Z., Hezaveh, S. J. G., Razmpoosh, E., Asghari-Jafarabadi, M. & Gargari, B. P. The effects of synbiotic supplementation on insulin resistance\/sensitivity, lipid profile and total antioxidant capacity in women with gestational diabetes mellitus: A randomized double blind placebo controlled clinical trial. Diabetes Res. Clin. Pract. 138, 149\u2013157 (2018).","journal-title":"Diabetes Res. Clin. Pract."}],"container-title":["npj Science of Food"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41538-026-00986-2","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41538-026-00986-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41538-026-00986-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T02:03:26Z","timestamp":1793671406000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41538-026-00986-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,11]]},"references-count":93,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["986"],"URL":"https:\/\/doi.org\/10.1038\/s41538-026-00986-2","relation":{},"ISSN":["2396-8370"],"issn-type":[{"value":"2396-8370","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,11]]},"assertion":[{"value":"12 January 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 June 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 July 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Ethics"}}],"article-number":"343"}}