{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T22:39:31Z","timestamp":1793399971714,"version":"4.5.0"},"reference-count":125,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T00:00:00Z","timestamp":1764115200000},"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>The gastrointestinal tract in humans hosts trillions of microorganisms, collectively termed the gut microbiota, which perform essential physiological processes and roles, including nutrient metabolism and immunomodulation. Influenced by genetics, age, diet, medication, and the environment, the disruption of this system leads to dysbiosis, which has been linked to a range of diseases, notably type 2 diabetes mellitus (T2DM). As the global prevalence of T2DM continues to trend upwards, research investigating and highlighting the influence the gut microbiome exerts on this disease is warranted. The literature was examined regarding microbial metabolites and metabolic signaling pathways, as well as interventions relating to diet, prebiotics, probiotics, pharmacological agents, and fecal microbiota transplantation (FMT). The gut microbiome, through its effects on insulin resistance, inflammation, bile acid signaling, and glucose\u2013lipid metabolism, impacts the development and progression of T2DM. Furthermore, patients with T2DM have demonstrated reduced microbial diversity, depletion of butyrate-producing bacteria, and an increase in pathogenic species. Interventions including high-fiber diets, metformin, probiotics, and FMT were shown to enrich beneficial microbes and improve metabolic outcomes. Targeted modulation of the microbiome, such as through next-generation probiotics and CRISPR-based therapies, may enhance metabolic control in the context of the future of personalized medicine. This review investigates the intricate relationship between the gut microbiome and T2DM, emphasizing its role in disease pathogenesis, the factors that may impact the microbiome in these patients, as well as therapeutic approaches toward its management.<\/jats:p>","DOI":"10.3390\/ijms262311412","type":"journal-article","created":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T10:04:57Z","timestamp":1764151497000},"page":"11412","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["The Role of the Gut Microbiome in Type 2 Diabetes Mellitus"],"prefix":"10.3390","volume":"26","author":[{"given":"Rahaf","family":"Mashal","sequence":"first","affiliation":[{"name":"School of Medicine, Royal College of Surgeons in Ireland\u2014Medical University of Bahrain, Busaiteen P.O. Box 15503, Bahrain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amnah","family":"Al-Muhanna","sequence":"additional","affiliation":[{"name":"School of Medicine, Royal College of Surgeons in Ireland\u2014Medical University of Bahrain, Busaiteen P.O. Box 15503, Bahrain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salma","family":"Khader","sequence":"additional","affiliation":[{"name":"School of Medicine, Royal College of Surgeons in Ireland\u2014Medical University of Bahrain, Busaiteen P.O. Box 15503, Bahrain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-6324-7920","authenticated-orcid":false,"given":"Aiman","family":"Khudair","sequence":"additional","affiliation":[{"name":"School of Medicine, Royal College of Surgeons in Ireland\u2014Medical University of Bahrain, Busaiteen P.O. Box 15503, Bahrain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-1739-9136","authenticated-orcid":false,"given":"Ahmed","family":"Khudair","sequence":"additional","affiliation":[{"name":"School of Medicine, Royal College of Surgeons in Ireland\u2014Medical University of Bahrain, Busaiteen P.O. Box 15503, Bahrain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5762-3917","authenticated-orcid":false,"given":"Alexandra E.","family":"Butler","sequence":"additional","affiliation":[{"name":"Research Department, Royal College of Surgeons in Ireland\u2014Medical University of Bahrain, Busaiteen P.O. Box 15503, Bahrain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Al Bander, Z., Nitert, M.D., Mousa, A., and Naderpoor, N. (2020). The Gut Microbiota and Inflammation: An Overview. Int. J. Environ. Res. Public Health, 17.","DOI":"10.3390\/ijerph17207618"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1823","DOI":"10.1042\/BCJ20160510","article-title":"Introduction to the human gut microbiota","volume":"474","author":"Thursby","year":"2017","journal-title":"Biochem. J."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1053\/j.gastro.2008.10.080","article-title":"Microbes in Gastrointestinal Health and Disease","volume":"136","author":"Neish","year":"2009","journal-title":"Gastroenterology"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1915","DOI":"10.1126\/science.1104816","article-title":"Host-Bacterial Mutualism in the Human Intestine","volume":"307","author":"Ley","year":"2005","journal-title":"Science"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1020","DOI":"10.1136\/gutjnl-2021-326789","article-title":"Gut microbiome and health: Mechanistic insights","volume":"71","author":"Tilg","year":"2022","journal-title":"Gut"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"e00302-24","DOI":"10.1128\/iai.00302-24","article-title":"The human gut microbiome in health and disease: Time for a new chapter?","volume":"92","author":"Lee","year":"2024","journal-title":"Infect. Immun."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1038\/s41392-022-00974-4","article-title":"Microbiota in health and diseases","volume":"7","author":"Hou","year":"2022","journal-title":"Signal. Transduct. Target. Ther."},{"key":"ref_8","first-page":"17","article-title":"Part 1: The Human Gut Microbiome in Health and Disease","volume":"13","author":"Bull","year":"2014","journal-title":"Integr. Med. Encinitas Calif."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1186\/s13099-021-00446-0","article-title":"Gut microbiota influence in type 2 diabetes mellitus (T2DM)","volume":"13","author":"Cunningham","year":"2021","journal-title":"Gut Pathog."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Zhang, P. (2022). Influence of Foods and Nutrition on the Gut Microbiome and Implications for Intestinal Health. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23179588"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1097\/MOG.0000000000000139","article-title":"The gut microbiome in health and in disease","volume":"31","author":"Shreiner","year":"2015","journal-title":"Curr. Opin. Gastroenterol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1470","DOI":"10.1053\/j.gastro.2014.03.001","article-title":"The Intestinal Metabolome: An Intersection Between Microbiota and Host","volume":"146","author":"Ursell","year":"2014","journal-title":"Gastroenterology"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"8787","DOI":"10.3748\/wjg.v21.i29.8787","article-title":"Role of the normal gut microbiota","volume":"21","author":"Jandhyala","year":"2015","journal-title":"World. J. Gastroenterol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"k2179","DOI":"10.1136\/bmj.k2179","article-title":"Role of the gut microbiota in nutrition and health","volume":"361","author":"Valdes","year":"2018","journal-title":"BMJ"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1016\/j.cell.2014.09.053","article-title":"Human Genetics Shape the Gut Microbiome","volume":"159","author":"Goodrich","year":"2014","journal-title":"Cell"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"734","DOI":"10.1177\/0884533615609899","article-title":"Gut Microbiome: What We Do and Don\u2019t Know","volume":"30","author":"Cresci","year":"2015","journal-title":"Nutr. Clin. Pract."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Alagiakrishnan, K., Morgadinho, J., and Halverson, T. (2024). Approach to the diagnosis and management of dysbiosis. Front. Nutr., 11.","DOI":"10.3389\/fnut.2024.1330903"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1137","DOI":"10.1097\/MIB.0000000000000750","article-title":"Current Understanding of Dysbiosis in Disease in Human and Animal Models","volume":"22","author":"DeGruttola","year":"2016","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"488","DOI":"10.15585\/mmwr.mm7218a3","article-title":"Provisional Mortality Data\u2014United States, 2022","volume":"72","author":"Ahmad","year":"2023","journal-title":"MMWR Morb. Mortal. Wkly. Rep."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1245","DOI":"10.1038\/ncomms2266","article-title":"Symptomatic atherosclerosis is associated with an altered gut metagenome","volume":"3","author":"Karlsson","year":"2012","journal-title":"Nat. Commun."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1126\/science.1224820","article-title":"Intestinal Inflammation Targets Cancer-Inducing Activity of the Microbiota","volume":"338","author":"Arthur","year":"2012","journal-title":"Science"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1038\/nature11450","article-title":"A metagenome-wide association study of gut microbiota in type 2 diabetes","volume":"490","author":"Qin","year":"2012","journal-title":"Nature"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1016","DOI":"10.1038\/nm.2015","article-title":"A human colonic commensal promotes colon tumorigenesis via activation of T helper type 17 T cell responses","volume":"15","author":"Wu","year":"2009","journal-title":"Nat. Med."},{"key":"ref_24","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_25","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1001\/jama.2025.5956","article-title":"Diagnosis and Treatment of Type 2 Diabetes in Adults: A Review","volume":"334","author":"Kalyani","year":"2025","journal-title":"JAMA"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/S0140-6736(23)01301-6","article-title":"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","volume":"402","author":"Ong","year":"2023","journal-title":"Lancet"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"543","DOI":"10.7326\/0003-4819-159-8-201310150-00007","article-title":"Lifestyle Interventions for Patients with and at Risk for Type 2 Diabetes: A Systematic Review and Meta-analysis","volume":"159","author":"Schellenberg","year":"2013","journal-title":"Ann. Intern. Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"790","DOI":"10.1056\/NEJMoa010492","article-title":"Diet, Lifestyle, and the Risk of Type 2 Diabetes Mellitus in Women","volume":"345","author":"Hu","year":"2001","journal-title":"N. Engl. J. Med."},{"key":"ref_29","unstructured":"Goyal, R., Singhal, M., and Jialal, I. (2025, August 06). Type 2 Diabetes, StatPearls [Internet], Available online: http:\/\/www.ncbi.nlm.nih.gov\/books\/NBK513253\/."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Dash, N.R., Al Bataineh, M.T., Alili, R., Al Safar, H., Alkhayyal, N., Prifti, E., Zucker, J.-D., Belda, E., and Cl\u00e9ment, K. (2023). Functional alterations and predictive capacity of gut microbiome in type 2 diabetes. Sci. Rep., 13.","DOI":"10.1038\/s41598-023-49679-w"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.jnutbio.2018.10.003","article-title":"Gut microbiome and type 2 diabetes: Where we are and where to go?","volume":"63","author":"Sharma","year":"2019","journal-title":"J. Nutr. Biochem."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1097\/IM9.0000000000000011","article-title":"Dysbiosis of Gut Microbiota Contributes to the Development of Diabetes Mellitus","volume":"1","author":"Lu","year":"2019","journal-title":"Infect. Microbes. Dis."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1280","DOI":"10.1016\/j.chom.2024.07.017","article-title":"The central role of the gut microbiota in the pathophysiology and management of type 2 diabetes","volume":"32","author":"Baars","year":"2024","journal-title":"Cell. Host. Microbe."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Zhou, Z., Sun, B., Yu, D., and Zhu, C. (2022). Gut Microbiota: An Important Player in Type 2 Diabetes Mellitus. Front. Cell. Infect. Microbiol., 12.","DOI":"10.3389\/fcimb.2022.834485"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Kashtanova, D.A., Tkacheva, O.N., Doudinskaya, E.N., Strazhesko, I.D., Kotovskaya, Y.V., Popenko, A.S., Tyakht, A.V., and Alexeev, D.G. (2018). Gut Microbiota in Patients with Different Metabolic Statuses: Moscow Study. Microorganisms, 6.","DOI":"10.3390\/microorganisms6040098"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Takagi, T., Naito, Y., Kashiwagi, S., Uchiyama, K., Mizushima, K., Kamada, K., Ishikawa, T., Inoue, R., Okuda, K., and Tsujimoto, Y. (2020). Changes in the Gut Microbiota are Associated with Hypertension, Hyperlipidemia, and Type 2 Diabetes Mellitus in Japanese Subjects. Nutrients, 12.","DOI":"10.3390\/nu12102996"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.nut.2018.11.019","article-title":"The alteration of gut microbiota in newly diagnosed type 2 diabetic patients","volume":"63\u201364","author":"Chen","year":"2019","journal-title":"Nutrition"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1532","DOI":"10.1038\/s41591-018-0164-x","article-title":"Regional variation limits applications of healthy gut microbiome reference ranges and disease models","volume":"24","author":"He","year":"2018","journal-title":"Nat. Med."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Chong, S., Lin, M., Chong, D., Jensen, S., and Lau, N.S. (2025). A systematic review on gut microbiota in type 2 diabetes mellitus. Front. Endocrinol., 15.","DOI":"10.3389\/fendo.2024.1486793"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Crudele, L., Gadaleta, R.M., Cariello, M., and Moschetta, A. (2023). Gut microbiota in the pathogenesis and therapeutic approaches of diabetes. eBioMedicine, 97.","DOI":"10.1016\/j.ebiom.2023.104821"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"10452","DOI":"10.1073\/pnas.1734063100","article-title":"Honor thy symbionts","volume":"100","author":"Xu","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/j.cmet.2010.07.001","article-title":"Our Unindicted Coconspirators: Human Metabolism from a Microbial Perspective","volume":"12","author":"Goodman","year":"2010","journal-title":"Cell. Metab."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"5281","DOI":"10.1007\/s00203-021-02516-y","article-title":"Structural diversity, functional aspects and future therapeutic applications of human gut microbiome","volume":"203","author":"Ghosh","year":"2021","journal-title":"Arch. Microbiol."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Kho, Z.Y., and Lal, S.K. (2018). The Human Gut Microbiome\u2014A Potential Controller of Wellness and Disease. Front. Microbiol., 9.","DOI":"10.3389\/fmicb.2018.01835"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Thomas, C.M., Hong, T., Van Pijkeren, J.P., Hemarajata, P., Trinh, D.V., Hu, W., Britton, R.A., Kalkum, M., and Versalovic, J. (2012). Histamine Derived from Probiotic Lactobacillus reuteri Suppresses TNF via Modulation of PKA and ERK Signaling. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0031951"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1073\/pnas.0906112107","article-title":"The bacterial signal indole increases epithelial-cell tight-junction resistance and attenuates indicators of inflammation","volume":"107","author":"Bansal","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Hrncir, T. (2022). Gut Microbiota Dysbiosis: Triggers, Consequences, Diagnostic and Therapeutic Options. Microorganisms, 10.","DOI":"10.3390\/microorganisms10030578"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1097\/ACI.0b013e328349b166","article-title":"Early life exposures: Impact on asthma and allergic disease","volume":"11","author":"Kozyrskyj","year":"2011","journal-title":"Curr. Opin. Allergy Clin. Immunol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"143","DOI":"10.2147\/ITT.S61528","article-title":"The hygiene hypothesis: Current perspectives and future therapies","volume":"4","author":"Stiemsma","year":"2015","journal-title":"ImmunoTargets Ther."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1186\/s13073-021-01007-5","article-title":"Population study of the gut microbiome: Associations with diet, lifestyle, and cardiometabolic disease","volume":"13","author":"Walker","year":"2021","journal-title":"Genome Med."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"967","DOI":"10.1101\/gr.278637.123","article-title":"Global compositional and functional states of the human gut microbiome in health and disease","volume":"34","author":"Lee","year":"2024","journal-title":"Genome Res."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1501","DOI":"10.1038\/s12276-024-01262-7","article-title":"Genome-resolved metagenomics: A game changer for microbiome medicine","volume":"56","author":"Kim","year":"2024","journal-title":"Exp. Mol. Med."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"2359677","DOI":"10.1080\/19490976.2024.2359677","article-title":"The human gut microbiome and aging","volume":"16","author":"Bradley","year":"2024","journal-title":"Gut Microbes"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"444","DOI":"10.1111\/dom.12637","article-title":"Effect of antibiotics on gut microbiota, glucose metabolism and body weight regulation: A review of the literature","volume":"18","author":"Mikkelsen","year":"2016","journal-title":"Diabetes Obes. Metab."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1016\/j.jaci.2022.07.015","article-title":"Enteric nervous system and intestinal epithelial regulation of the gut-brain axis","volume":"150","author":"Dowling","year":"2022","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.humic.2016.09.001","article-title":"Diet influence on the gut microbiota and dysbiosis related to nutritional disorders","volume":"1","author":"Lagier","year":"2016","journal-title":"Hum. Microbiome J."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Patangia, D.V., Anthony Ryan, C., Dempsey, E., Paul Ross, R., and Stanton, C. (2022). Impact of antibiotics on the human microbiome and consequences for host health. MicrobiologyOpen, 11.","DOI":"10.1002\/mbo3.1260"},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Larsen, O.F.A., Van Der Grint, M., Wiegers, C., and Van De Burgwal, L.H.M. (2022). The Gut Microbiota: Master of Puppets Connecting the Epidemiology of Infectious, Autoimmune, and Metabolic Disease. Front. Microbiol., 13.","DOI":"10.3389\/fmicb.2022.902106"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"e2118811","DOI":"10.1001\/jamanetworkopen.2021.18811","article-title":"Association of Insulin Resistance and Type 2 Diabetes with Gut Microbial Diversity: A Microbiome-Wide Analysis from Population Studies","volume":"4","author":"Chen","year":"2021","journal-title":"JAMA Netw. Open"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1126\/science.1241165","article-title":"The microbial metabolites, short-chain fatty acids, regulate colonic Treg cell homeostasis","volume":"341","author":"Smith","year":"2013","journal-title":"Science"},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Wu, J., Yang, K., Fan, H., Wei, M., and Xiong, Q. (2023). Targeting the gut microbiota and its metabolites for type 2 diabetes mellitus. Front. Endocrinol., 14.","DOI":"10.3389\/fendo.2023.1114424"},{"key":"ref_62","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_63","doi-asserted-by":"crossref","first-page":"2325","DOI":"10.1194\/jlr.R036012","article-title":"The role of short-chain fatty acids in the interplay between diet, gut microbiota, and host energy metabolism","volume":"54","author":"Groen","year":"2013","journal-title":"J. Lipid Res."},{"key":"ref_64","first-page":"e41559","article-title":"Understanding the Role of the Gut Microbiome in Diabetes and Therapeutics Targeting Leaky Gut: A Systematic Review","volume":"15","author":"Sadagopan","year":"2023","journal-title":"Cureus"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"418","DOI":"10.1016\/j.nut.2013.09.005","article-title":"Oligofructose-enriched inulin improves some inflammatory markers and metabolic endotoxemia in women with type 2 diabetes mellitus: A randomized controlled clinical trial","volume":"30","author":"Dehghan","year":"2014","journal-title":"Nutrition"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1007\/s13668-020-00307-3","article-title":"Metabolites Linking the Gut Microbiome with Risk for Type 2 Diabetes","volume":"9","author":"Zhu","year":"2020","journal-title":"Curr. Nutr. Rep."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1016\/j.cmet.2017.09.008","article-title":"Improvement of Insulin Sensitivity after Lean Donor Feces in Metabolic Syndrome Is Driven by Baseline Intestinal Microbiota Composition","volume":"26","author":"Kootte","year":"2017","journal-title":"Cell Metab."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1481","DOI":"10.1038\/nm.2513","article-title":"Interleukin-6 enhances insulin secretion by increasing glucagon-like peptide-1 secretion from L cells and alpha cells","volume":"17","author":"Ellingsgaard","year":"2011","journal-title":"Nat. Med."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1038\/nature18646","article-title":"Human gut microbes impact host serum metabolome and insulin sensitivity","volume":"535","author":"Pedersen","year":"2016","journal-title":"Nature"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1038\/nature09922","article-title":"Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease","volume":"472","author":"Wang","year":"2011","journal-title":"Nature"},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Gao, R., Meng, X., Xue, Y., Mao, M., Liu, Y., Tian, X., Sui, B., Li, X., and Zhang, P. (2022). Bile acids-gut microbiota crosstalk contributes to the improvement of type 2 diabetes mellitus. Front. Pharmacol., 13.","DOI":"10.3389\/fphar.2022.1027212"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"171216","DOI":"10.1016\/j.peptides.2024.171216","article-title":"Incretin hormones, obesity and gut microbiota","volume":"178","author":"Angelini","year":"2024","journal-title":"Peptides"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1131","DOI":"10.1007\/s00592-021-01727-5","article-title":"The relationship between gut microbiota, short-chain fatty acids and type 2 diabetes mellitus: The possible role of dietary fibre","volume":"58","author":"Salamone","year":"2021","journal-title":"Acta Diabetol."},{"key":"ref_74","first-page":"E87","article-title":"The role of mediterranean diet and gut microbiota in type- diabetes mellitus associated with obesity (diabesity)","volume":"63","author":"Sultanoglu","year":"2022","journal-title":"J. Prev. Med. Hyg."},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Xu, X., Zhang, F., Ren, J., Zhang, H., Jing, C., Wei, M., Jiang, Y., and Xie, H. (2024). Dietary intervention improves metabolic levels in patients with type 2 diabetes through the gut microbiota: A systematic review and meta-analysis. Front. Nutr., 10, Erratum in: Front Nutr. 2024, 11, 1414687.","DOI":"10.3389\/fnut.2024.1414687"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"200286","DOI":"10.1016\/j.hnm.2024.200286","article-title":"Diet and gut microbiome: Impact of each factor and mutual interactions on prevention and treatment of type 1, type 2, and gestational diabetes mellitus","volume":"38","author":"Menafra","year":"2024","journal-title":"Hum. Nutr. Metab."},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Fu, J., Zheng, Y., Gao, Y., and Xu, W. (2022). Dietary Fiber Intake and Gut Microbiota in Human Health. Microorganisms, 10.","DOI":"10.3390\/microorganisms10122507"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1038\/s41467-019-14177-z","article-title":"Impact of commonly used drugs on the composition and metabolic function of the gut microbiota","volume":"11","author":"Collij","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"850","DOI":"10.1038\/nm.4345","article-title":"Metformin alters the gut microbiome of individuals with treatment-naive type 2 diabetes, contributing to the therapeutic effects of the drug","volume":"23","author":"Wu","year":"2017","journal-title":"Nat. Med."},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"Kim, H.B., Cho, Y.J., and Choi, S.S. (2024). Metformin increases gut multidrug resistance genes in type 2 diabetes, potentially linked to Escherichia coli. Sci. Rep., 14.","DOI":"10.1038\/s41598-024-72467-z"},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Yang, Q., Liang, Q., Balakrishnan, B., Belobrajdic, D.P., Feng, Q.J., and Zhang, W. (2020). Role of Dietary Nutrients in the Modulation of Gut Microbiota: A Narrative Review. Nutrients, 12.","DOI":"10.3390\/nu12020381"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1093\/nutrit\/nuz072","article-title":"Dietary fiber and its associations with depression and inflammation","volume":"78","author":"Swann","year":"2020","journal-title":"Nutr. Rev."},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Soliman, G.A. (2019). Dietary Fiber, Atherosclerosis, and Cardiovascular Disease. Nutrients, 11.","DOI":"10.3390\/nu11051155"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1418","DOI":"10.1093\/ajcn\/53.6.1418","article-title":"Fermentability of various fiber sources by human fecal bacteria in vitro","volume":"53","author":"Titgemeyer","year":"1991","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Portincasa, P., Bonfrate, L., Vacca, M., De Angelis, M., Farella, I., Lanza, E., Khalil, M., Wang, D.Q.-H., Sperandio, M., and Di Ciaula, A. (2022). Gut Microbiota and Short Chain Fatty Acids: Implications in Glucose Homeostasis. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23031105"},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Diniz Do Nascimento, L., Moraes, A.A.B.D., Costa, K.S.D., Pereira Gal\u00facio, J.M., Taube, P.S., Costa, C.M.L., Cruz, J.N., Andrade, E.H.D.A., and De Faria, L.J.G. (2020). Bioactive Natural Compounds and Antioxidant Activity of Essential Oils from Spice Plants: New Findings and Potential Applications. Biomolecules, 10.","DOI":"10.3390\/biom10070988"},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"Sobiecki, J.G., Imamura, F., Davis, C.R., Sharp, S.J., Koulman, A., Hodgson, J.M., Guevara, M., Schulze, M.B., Zheng, J.-S., and Agnoli, C. (2023). A nutritional biomarker score of the Mediterranean diet and incident type 2 diabetes: Integrated analysis of data from the MedLey randomised controlled trial and the EPIC-InterAct case-cohort study. Popkin BM, editor. PLoS Med., 20.","DOI":"10.1371\/journal.pmed.1004221"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"5003","DOI":"10.2147\/DMSO.S286430","article-title":"Effects of Metformin on the Gut Microbiota in Obesity and Type 2 Diabetes Mellitus","volume":"13","author":"Zhang","year":"2020","journal-title":"Diabetes Metab. Syndr. Obes. Targets Ther."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1097\/NT.0000000000000228","article-title":"Mediterranean Diet and Prevention of Chronic Diseases","volume":"52","author":"Romagnolo","year":"2017","journal-title":"Nutr. Today"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"257","DOI":"10.5946\/ce.2015.117","article-title":"Fecal Microbiota Transplantation: Current Applications, Effectiveness, and Future Perspectives","volume":"49","author":"Choi","year":"2016","journal-title":"Clin. Endosc."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"137","DOI":"10.5946\/ce.2019.009","article-title":"Fecal Microbiota Transplantation: An Update on Clinical Practice","volume":"52","author":"Kim","year":"2019","journal-title":"Clin. Endosc."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1111\/dom.13561","article-title":"Gut microbiota and obesity: An opportunity to alter obesity through faecal microbiota transplant (FMT)","volume":"21","author":"Lee","year":"2019","journal-title":"Diabetes Obes. Metab."},{"key":"ref_93","doi-asserted-by":"crossref","unstructured":"Bibb\u00f2, S., Settanni, C.R., Porcari, S., Bocchino, E., Ianiro, G., Cammarota, G., and Gasbarrini, A. (2020). Fecal Microbiota Transplantation: Screening and Selection to Choose the Optimal Donor. J. Clin. Med., 9.","DOI":"10.3390\/jcm9061757"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"E431","DOI":"10.1503\/cmaj.150672","article-title":"Seeking safe stool: Canada needs a universal donor model","volume":"188","author":"Edelstein","year":"2016","journal-title":"Can. Med. Assoc. J."},{"key":"ref_95","doi-asserted-by":"crossref","unstructured":"De Angelis, M., Ferrocino, I., Calabrese, F.M., De Filippis, F., Cavallo, N., Siragusa, S., Rampelli, S., Di Cagno, R., Rantsiou, K., and Vannini, L. (2020). Diet influences the functions of the human intestinal microbiome. Sci. Rep., 10.","DOI":"10.1038\/s41598-020-61192-y"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0928-0987(01)00209-3","article-title":"Probiotics: Potential pharmaceutical applications","volume":"15","author":"Kaur","year":"2002","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"3044","DOI":"10.12659\/MSM.902600","article-title":"Effect of Probiotics on Glucose and Lipid Metabolism in Type 2 Diabetes Mellitus: A Meta-Analysis of 12 Randomized Controlled Trials","volume":"23","author":"Yao","year":"2017","journal-title":"Med. Sci. Monit."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1080\/19390211.2025.2522463","article-title":"Efficacy of a Probiotic Combination on Glycemic Index and Insulin Resistance in Adults: A Systematic Review and Meta-Analysis","volume":"22","author":"Dubey","year":"2025","journal-title":"J. Diet. Suppl."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"9066","DOI":"10.1073\/pnas.1219451110","article-title":"Cross-talk between Akkermansia. muciniphila and intestinal epithelium controls diet-induced obesity","volume":"110","author":"Everard","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_100","doi-asserted-by":"crossref","unstructured":"Sako, T., and Tanaka, R. (2011). Prebiotics|Functions. Encyclopedia of Dairy Sciences, Elsevier.","DOI":"10.1016\/B978-0-12-374407-4.00427-1"},{"key":"ref_101","doi-asserted-by":"crossref","unstructured":"Iatcu, O.C., Hamamah, S., and Covasa, M. (2024). Harnessing Prebiotics to Improve Type 2 Diabetes Outcomes. Nutrients, 16.","DOI":"10.3390\/nu16203447"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"1502","DOI":"10.4239\/wjd.v14.i10.1502","article-title":"Gut microbiome supplementation as therapy for metabolic syndrome","volume":"14","author":"Antony","year":"2023","journal-title":"World J. Diabetes"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"99","DOI":"10.2174\/1871530316666160831093813","article-title":"Gut Microbiota of Obese, Type 2 Diabetic Individuals is Enriched in Faecalibacterium prausnitzii, Akkermansia muciniphila and Peptostreptococcus anaerobius after Weight Loss","volume":"16","author":"Remely","year":"2016","journal-title":"Endocr. Metab. Immune Disord."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1007\/s00508-015-0755-1","article-title":"Increased gut microbiota diversity and abundance of Faecalibacterium prausnitzii and Akkermansia after fasting: A pilot study","volume":"127","author":"Remely","year":"2015","journal-title":"Wien. Klin. Wochenschr."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1038\/s41575-021-00440-6","article-title":"The International Scientific Association of Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of postbiotics","volume":"18","author":"Salminen","year":"2021","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"5869","DOI":"10.1007\/s12649-021-01429-7","article-title":"Fermentation Optimization for Co-production of Postbiotics by Bifidobacterium lactis BB12 in Cheese Whey","volume":"12","author":"Amiri","year":"2021","journal-title":"Waste Biomass Valorization"},{"key":"ref_107","doi-asserted-by":"crossref","unstructured":"Dini\u0107, M., Luki\u0107, J., Djoki\u0107, J., Milenkovi\u0107, M., Strahini\u0107, I., Goli\u0107, N., and Begovi\u0107, J. (2017). Lactobacillus fermentum Postbiotic-induced Autophagy as Potential Approach for Treatment of Acetaminophen Hepatotoxicity. Front. Microbiol., 8.","DOI":"10.3389\/fmicb.2017.00594"},{"key":"ref_108","doi-asserted-by":"crossref","unstructured":"Gofron, K.K., Wasilewski, A., and Ma\u0142gorzewicz, S. (2025). Effects of GLP-1 Analogues and Agonists on the Gut Microbiota: A Systematic Review. Nutrients, 17.","DOI":"10.3390\/nu17081303"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"e000717","DOI":"10.1136\/bmjdrc-2019-000717","article-title":"Effects of metformin, acarbose, and sitagliptin monotherapy on gut microbiota in Zucker diabetic fatty rats","volume":"7","author":"Zhang","year":"2019","journal-title":"BMJ Open Diabetes Res. Care"},{"key":"ref_110","doi-asserted-by":"crossref","unstructured":"Huda, M.N., Kim, M., and Bennett, B.J. (2021). Modulating the Microbiota as a Therapeutic Intervention for Type 2 Diabetes. Front. Endocrinol., 12.","DOI":"10.3389\/fendo.2021.632335"},{"key":"ref_111","doi-asserted-by":"crossref","unstructured":"Liu, W., Luo, Z., Zhou, J., and Sun, B. (2022). Gut Microbiota and Antidiabetic Drugs: Perspectives of Personalized Treatment in Type 2 Diabetes Mellitus. Front. Cell. Infect. Microbiol., 12.","DOI":"10.3389\/fcimb.2022.853771"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"722","DOI":"10.1093\/advances\/nmaa133","article-title":"Probiotics Contribute to Glycemic Control in Patients with Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis","volume":"12","author":"Rittiphairoj","year":"2021","journal-title":"Adv. Nutr."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1016\/j.clnu.2024.11.042","article-title":"Effects of synbiotics surpass probiotics alone in improving type 2 diabetes mellitus: A randomized, double-blind, placebo-controlled trial","volume":"44","author":"Zhang","year":"2025","journal-title":"Clin. Nutr."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"306","DOI":"10.7326\/0003-4819-151-5-200909010-00004","article-title":"Effects of a Mediterranean-Style Diet on the Need for Antihyperglycemic Drug Therapy in Patients with Newly Diagnosed Type 2 Diabetes: A Randomized Trial","volume":"151","author":"Esposito","year":"2009","journal-title":"Ann. Intern. Med."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"740","DOI":"10.1016\/j.numecd.2010.03.005","article-title":"Can the Mediterranean diet lower HbA1c in type 2 diabetes? Results from a randomized cross-over study","volume":"21","author":"Itsiopoulos","year":"2011","journal-title":"Nutr. Metab. Cardiovasc. Dis."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"1151","DOI":"10.1126\/science.aao5774","article-title":"Gut bacteria selectively promoted by dietary fibers alleviate type 2 diabetes","volume":"359","author":"Zhao","year":"2018","journal-title":"Science"},{"key":"ref_117","doi-asserted-by":"crossref","unstructured":"Markowiak, P., and \u015ali\u017cewska, K. (2017). Effects of Probiotics, Prebiotics, and Synbiotics on Human Health. Nutrients, 9.","DOI":"10.3390\/nu9091021"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1038\/s41575-018-0061-2","article-title":"You are what you eat: Diet, health and the gut microbiota","volume":"16","author":"Zmora","year":"2019","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"27679","DOI":"10.1021\/acs.jafc.4c08702","article-title":"Next-Generation Probiotics and Chronic Diseases: A Review of Current Research and Future Directions","volume":"72","author":"Tiwari","year":"2024","journal-title":"J. Agric. Food. Chem."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1016\/j.idairyj.2009.11.010","article-title":"Gut microbiota: Changes throughout the lifespan from infancy to elderly","volume":"20","author":"Claesson","year":"2010","journal-title":"Int. Dairy. J."},{"key":"ref_121","doi-asserted-by":"crossref","unstructured":"MetaHITConsortium, Qin, J., Li, R., Raes, J., Arumugam, M., Burgdorf, K.S., Manichanh, C., Nielsen, T., Pons, N., and Levenez, F. (2010). A human gut microbial gene catalogue established by metagenomic sequencing. Nature, 464, 59\u201365.","DOI":"10.1038\/nature08821"},{"key":"ref_122","doi-asserted-by":"crossref","unstructured":"Zhang, H., Duan, Y., Cai, F., Cao, D., Wang, L., Qiao, Z., Hong, Q., Li, N., Zheng, Y., and Su, M. (2022). Next-Generation Probiotics: Microflora Intervention to Human Diseases. BioMed. Res. Int., 2022.","DOI":"10.1155\/2022\/5633403"},{"key":"ref_123","doi-asserted-by":"crossref","unstructured":"Mu, Y., Zhang, C., Li, T., Jin, F.J., Sung, Y.J., Oh, H.M., Lee, H.-G., and Jin, L. (2022). Development and Applications of CRISPR\/Cas9-Based Genome Editing in Lactobacillus. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms232112852"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/j.mib.2017.05.015","article-title":"CRISPR-based engineering of next-generation lactic acid bacteria","volume":"37","author":"Barrangou","year":"2017","journal-title":"Curr. Opin. Microbiol."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1007\/s10142-025-01625-x","article-title":"Genome-resolved metagenomics from short-read sequencing data in the era of artificial intelligence","volume":"25","author":"Qayyum","year":"2025","journal-title":"Funct. Integr. Genom."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/23\/11412\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T10:08:22Z","timestamp":1764151702000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/23\/11412"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,26]]},"references-count":125,"journal-issue":{"issue":"23","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["ijms262311412"],"URL":"https:\/\/doi.org\/10.3390\/ijms262311412","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,26]]}}}