{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T22:12:04Z","timestamp":1785795124353,"version":"3.56.0"},"reference-count":68,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2025,3,28]],"date-time":"2025-03-28T00:00:00Z","timestamp":1743120000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institutes of Health (NIH\/NIA)","award":["5R01AG070934-05"],"award-info":[{"award-number":["5R01AG070934-05"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Gestational diabetes mellitus (GD)-induced gut dysbiosis in pregnant mothers may increase the risk of cognitive impairment and neurological disorders in both the mother and offspring as they age. Restoring gut balance could improve cognitive outcomes for both. Despite advancements in GD treatment, side effects have increased, and long-term neurocognitive impacts on offspring born to GD mothers remain underexplored. This study uses a GD mouse model, inducing pancreatic dysfunction in 3-month-old pregnant C57BL\/6J mice with Streptozotocin. The efficacy and mechanism of the prebiotic phytocompound green leaf extract (Allmania nodiflora) were assessed, with metformin as the standard. GD dams exhibited weight and glucose reduction, pancreatic IL-6 elevation, GLUT3 reduction, astroglia changes in the cerebral cortex, gut barrier impairment, cognitive impairment, and heightened anxiety compared to controls. Bacterial 16s rRNA sequencing revealed dysbiosis, with reduced Erysipelotrichales in GD dams compared to controls. Metformin lowered blood glucose levels but failed to rescue functional and behavioral phenotypes in both GD dams and offspring. Phytocompound treatment improved blood glucose, reduced pancreatic inflammation, improved gut barrier integrity, reversed dysbiosis, and enhanced brain health. It rescued behavioral deficits and improved cognitive outcomes in offspring, suggesting the prebiotic phytocompound may be a more effective therapeutic agent for GD in humans.<\/jats:p>","DOI":"10.3390\/ijms26073140","type":"journal-article","created":{"date-parts":[[2025,3,28]],"date-time":"2025-03-28T13:36:49Z","timestamp":1743169009000},"page":"3140","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Effects of Prebiotic Phytocompound Administration in Gestational Diabetic Dams and Its Influence on Offspring Cognitive Outcomes"],"prefix":"10.3390","volume":"26","author":[{"given":"Gayathri","family":"Jagadeesan","sequence":"first","affiliation":[{"name":"Department of Neurology, The University of Texas McGovern Medical School, Houston, TX 77030, USA"},{"name":"Bioprospecting Laboratory, Department of Botany, Bharathiar University, Coimbatore 641-046, Tamil Nadu, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tushar K.","family":"Das","sequence":"additional","affiliation":[{"name":"Department of Neurology, The University of Texas McGovern Medical School, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-2834-0618","authenticated-orcid":false,"given":"Jennifer M.","family":"Mendoza","sequence":"additional","affiliation":[{"name":"Department of Neurology, The University of Texas McGovern Medical School, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3927-8862","authenticated-orcid":false,"given":"Ghalya","family":"Alrousan","sequence":"additional","affiliation":[{"name":"Department of Neurology, The University of Texas McGovern Medical School, Houston, TX 77030, USA"},{"name":"The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria P.","family":"Blasco-Conesa","sequence":"additional","affiliation":[{"name":"Department of Neurology, The University of Texas McGovern Medical School, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Parimelazhagan","family":"Thangaraj","sequence":"additional","affiliation":[{"name":"Bioprospecting Laboratory, Department of Botany, Bharathiar University, Coimbatore 641-046, Tamil Nadu, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1575-7914","authenticated-orcid":false,"given":"Bhanu Priya","family":"Ganesh","sequence":"additional","affiliation":[{"name":"Department of Neurology, The University of Texas McGovern Medical School, Houston, TX 77030, USA"},{"name":"The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,3,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/S0140-6736(24)00825-0","article-title":"Epidemiology and Management of Gestational Diabetes","volume":"404","author":"Sweeting","year":"2024","journal-title":"Lancet"},{"key":"ref_2","first-page":"e47500","article-title":"A Comprehensive Review of Gestational Diabetes Mellitus: Impacts on Maternal Health, Fetal Development, Childhood Outcomes, and Long-Term Treatment Strategies","volume":"15","author":"Nakshine","year":"2023","journal-title":"Cureus"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1016\/j.tem.2018.09.004","article-title":"Gestational Diabetes Mellitus: Mechanisms, Treatment, and Complications","volume":"29","author":"Johns","year":"2018","journal-title":"Trends Endocrinol. Metab."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"105190","DOI":"10.1016\/j.earlhumdev.2020.105190","article-title":"Maternal Influences on Fetal Brain Development: The Role of Nutrition, Infection and Stress, and the Potential for Intergenerational Consequences","volume":"150","author":"Fitzgerald","year":"2020","journal-title":"Early Hum. Dev."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1038\/s41392-024-01746-y","article-title":"Gut Microbiome Regulates Inflammation and Insulin Resistance: A Novel Therapeutic Target to Improve Insulin Sensitivity","volume":"9","author":"Semo","year":"2024","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Biete, M., and Vasudevan, S. (2024). Gestational Diabetes Mellitus: Impacts on Fetal Neurodevelopment, Gut Dysbiosis, and the Promise of Precision Medicine. Front. Mol. Biosci., 11.","DOI":"10.3389\/fmolb.2024.1420664"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Ansari, P., Khan, J.T., Chowdhury, S., Reberio, A.D., Kumar, S., Seidel, V., Abdel-Wahab, Y.H.A., and Flatt, P.R. (2024). Plant-Based Diets and Phytochemicals in the Management of Diabetes Mellitus and Prevention of Its Complications: A Review. Nutrients, 16.","DOI":"10.20944\/preprints202408.1739.v1"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"131294","DOI":"10.1016\/j.foodchem.2021.131294","article-title":"Understanding the Bioaccessibility, \u03b1-Amylase and \u03b1-Glucosidase Enzyme Inhibition Kinetics of Allmania nodiflora (L.) R.Br. Ex Wight Polyphenols during in Vitro Simulated Digestion","volume":"372","author":"Jagadeesan","year":"2022","journal-title":"Food Chem."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1080\/19490976.2017.1290756","article-title":"Dietary Fiber and Prebiotics and the Gastrointestinal Microbiota","volume":"8","author":"Holscher","year":"2017","journal-title":"Gut Microbes"},{"key":"ref_10","first-page":"356","article-title":"The Streptozotocin-Induced Diabetic Nude Mouse Model: Differences between Animals from Different Sources","volume":"61","author":"Graham","year":"2011","journal-title":"Comp. Med"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Grupe, K., and Scherneck, S. (2023). Mouse Models of Gestational Diabetes Mellitus and Its Subtypes: Recent Insights and Pitfalls. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24065982"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"28","DOI":"10.2337\/diab.34.2.S28","article-title":"Is There an Animal Model for Gestational Diabetes?","volume":"34","author":"Hellerstrom","year":"1985","journal-title":"Diabetes"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"4235","DOI":"10.2147\/DMSO.S270935","article-title":"Research Progress on the Experimental Animal Model of Gestational Diabetes Mellitus","volume":"13","author":"He","year":"2020","journal-title":"Diabetes Metab. Syndr. Obes."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1111\/dom.14589","article-title":"Metformin versus Insulin Therapy for Gestational Diabetes: Effects on Offspring Anthropometrics and Metabolism at the Age of 9 Years: A Follow-up Study of Two Open-Label, Randomized Controlled Trials","volume":"24","author":"Paavilainen","year":"2022","journal-title":"Diabetes Obes. Metab."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1002\/ijgo.13380","article-title":"Follow-up of Offspring and Mothers with Gestational Diabetes Treated with Metformin or Glibenclamide: A Randomized Controlled Trial","volume":"152","author":"Paul","year":"2021","journal-title":"Int. J. Gynaecol. Obstet."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"825","DOI":"10.1111\/ajo.13739","article-title":"Metformin in Gestational Diabetes The Offspring Follow Up (MiGTOFU): Associations between Maternal Characteristics and Size and Adiposity of Boys and Girls at Nine Years","volume":"63","author":"Rowan","year":"2023","journal-title":"Aust. N. Z. J. Obstet. Gynaecol. J."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"e000456","DOI":"10.1136\/bmjdrc-2017-000456","article-title":"Metformin in Gestational Diabetes: The Offspring Follow-up (MiG TOFU): Body Composition and Metabolic Outcomes at 7\u20139 Years of Age","volume":"6","author":"Rowan","year":"2018","journal-title":"BMJ. Open Diabetes Res. Care"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Megur, A., Daliri, E.B.M., Baltriukien\u0117, D., and Burokas, A. (2022). 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.","DOI":"10.3390\/ijms23116097"},{"key":"ref_19","first-page":"e46741","article-title":"Probiotics and Their Role in the Management of Type 2 Diabetes Mellitus (Short-Term Versus Long-Term Effect): A Systematic Review and Meta-Analysis","volume":"15","author":"Ayesha","year":"2023","journal-title":"Cureus"},{"key":"ref_20","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_21","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1186\/s12974-023-02887-7","article-title":"Stabilizing Histamine Release in Gut Mast Cells Mitigates Peripheral and Central Inflammation after Stroke","volume":"20","author":"Conesa","year":"2023","journal-title":"J. Neuroinflammation"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Schneider, M.R., Dahlhoff, M., Horst, D., Hirschi, B., Tr\u00fclzsch, K., M\u00fcller-H\u00f6cker, J., Vogelmann, R., Allg\u00e4uer, M., Gerhard, M., and Steininger, S. (2010). A Key Role for E-Cadherin in Intestinal Homeostasis and Paneth Cell Maturation. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0014325"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/j.jneumeth.2014.02.001","article-title":"Burrowing and Nest Building Behavior as Indicators of Well-Being in Mice","volume":"234","author":"Jirkof","year":"2014","journal-title":"J. Neurosci. Methods"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1007\/978-1-4939-8994-2_10","article-title":"The Y-Maze for Assessment of Spatial Working and Reference Memory in Mice","volume":"1916","author":"Kraeuter","year":"2019","journal-title":"Methods Mol. Biol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1016\/j.tins.2015.04.003","article-title":"Glial Fibrillary Acidic Protein: From Intermediate Filament Assembly and Gliosis to Neurobiomarker","volume":"38","author":"Yang","year":"2015","journal-title":"Trends Neurosci."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"R69","DOI":"10.1530\/EJE-20-1101","article-title":"Metabolic Impact of Bile Acids in Gestation","volume":"184","author":"Fan","year":"2021","journal-title":"Eur. J. Endocrinol."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Neven, A.C.H., Mousa, A., Boyle, J.A., and Teede, H.J. (2023). Endocrine and Metabolic Interactions in Healthy Pregnancies and Hyperinsulinemic Pregnancies Affected by Polycystic Ovary Syndrome, Diabetes and Obesity. Front. Endocrinol., 13.","DOI":"10.3389\/fendo.2022.993619"},{"key":"ref_28","first-page":"CC01","article-title":"Normal Pregnancy\u2014A State of Insulin Resistance","volume":"8","author":"Sonagra","year":"2014","journal-title":"J. Clin. Diagn. Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"5320156","DOI":"10.1155\/2019\/5320156","article-title":"Review Article Determinants of Maternal Insulin Resistance during Pregnancy: An Updated Overview","volume":"2019","author":"Kampmann","year":"2019","journal-title":"J. Diabetes Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1007\/s13340-020-00425-x","article-title":"Pathophysiology of Gestational Diabetes Mellitus in Lean Japanese Pregnant Women in Relation to Insulin Secretion or Insulin Resistance","volume":"11","author":"Inoue","year":"2020","journal-title":"Diabetol. Int."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Plows, J.F., Stanley, J.L., Baker, P.N., Reynolds, C.M., and Vickers, M.H. (2018). The Pathophysiology of Gestational Diabetes Mellitus. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19113342"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"820","DOI":"10.1097\/FPC.0b013e3283559b22","article-title":"Metformin Pathways: Pharmacokinetics and Pharmacodynamics","volume":"22","author":"Gong","year":"2012","journal-title":"Pharmacogenet. Genom."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1577","DOI":"10.1007\/s00125-017-4342-z","article-title":"The Mechanisms of Action of Metformin","volume":"60","author":"Rena","year":"2017","journal-title":"Diabetologia"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1045","DOI":"10.4103\/1673-5374.385286","article-title":"Promising Use of Metformin in Treating Neurological Disorders: Biomarker-Guided Therapies","volume":"19","author":"Loan","year":"2023","journal-title":"Neural Regen. Res."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Tocci, V., Mirabelli, M., Salatino, A., Sicilia, L., Giuliano, S., Brunetti, F.S., Chiefari, E., De Sarro, G., Foti, D.P., and Brunetti, A. (2023). Metformin in Gestational Diabetes Mellitus: To Use or Not to Use, That Is the Question. Pharmaceuticals, 16.","DOI":"10.3390\/ph16091318"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Cheng, M., Ren, L., Jia, X., Wang, J., and Cong, B. (2024). Understanding the Action Mechanisms of Metformin in the Gastrointestinal Tract. Front. Pharmacol., 15.","DOI":"10.3389\/fphar.2024.1347047"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Kandpal, M., Indari, O., Baral, B., Jakhmola, S., Tiwari, D., Bhandari, V., Pandey, R.K., Bala, K., Sonawane, A., and Jha, H.C. (2022). Dysbiosis of Gut Microbiota from the Perspective of the Gut\u2013Brain Axis: Role in the Provocation of Neurological Disorders. Metabolites, 12.","DOI":"10.3390\/metabo12111064"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"100075","DOI":"10.1016\/j.bbih.2020.100075","article-title":"Sex Differences in Offspring Neurodevelopment, Cognitive Performance and Microglia Morphology Associated with Maternal Diabetes: Putative Targets for Insulin Therapy","volume":"5","author":"Sousa","year":"2020","journal-title":"Brain Behav. Immun. Health"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1021\/acs.chemrev.2c00431","article-title":"Microbiome and Human Health: Current Understanding, Engineering, and Enabling Technologies","volume":"123","author":"Aggarwal","year":"2023","journal-title":"Chem. Rev."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1097\/ANC.0000000000000218","article-title":"Maternal Microbiome and Pregnancy Outcomes That Impact Infant Health: A Review","volume":"15","author":"Dunlop","year":"2015","journal-title":"Adv. Neonatal Care"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1186\/s12967-023-04230-3","article-title":"Maternal Microbiota and Gestational Diabetes: Impact on Infant Health","volume":"21","author":"Singh","year":"2023","journal-title":"J. Transl. Med."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Mustad, V.A., Huynh, D.T.T., L\u00f3pez-Pedrosa, J.M., Campoy, C., and Rueda, R. (2020). The Role of Dietary Carbohydrates in Gestational Diabetes. Nutrients, 12.","DOI":"10.3390\/nu12020385"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"100136","DOI":"10.1016\/j.advnut.2023.10.008","article-title":"Roles of Diet-Associated Gut Microbial Metabolites on Brain Health: Cell-to-Cell Interactions between Gut Bacteria and the Central Nervous System","volume":"15","author":"Kim","year":"2024","journal-title":"Adv. Nutr."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"104719","DOI":"10.1016\/j.jff.2021.104719","article-title":"Recent Advances of Intestinal Microbiota Transmission from Mother to Infant","volume":"87","author":"Yang","year":"2021","journal-title":"J. Funct. Foods"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"S2000","DOI":"10.3945\/ajcn.110.001172","article-title":"Gut Microbiota and Probiotics in Maternal and Infant Health","volume":"94","author":"Sanz","year":"2011","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1097\/MPG.0000000000000347","article-title":"Lactobacilli and Bifidobacteria in Human Breast Milk: Influence of Antibiotherapy and Other Host and Clinical Factors","volume":"59","author":"Soto","year":"2014","journal-title":"J. Pediatr. Gastroenterol. Nutr."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/j.molmed.2014.12.002","article-title":"The Infant Microbiome Development: Mom Matters","volume":"21","author":"Mueller","year":"2015","journal-title":"Trends Mol. Med."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"8323","DOI":"10.1038\/s41467-024-52561-6","article-title":"Gut Microbiota Wellbeing Index Predicts Overall Health in a Cohort of 1000 Infants","volume":"15","author":"Hickman","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Pessa-Morikawa, T., Husso, A., K\u00e4rkk\u00e4inen, O., Koistinen, V., Hanhineva, K., Iivanainen, A., and Niku, M. (2022). Maternal Microbiota-Derived Metabolic Profile in Fetal Murine Intestine, Brain and Placenta. BMC Microbiol., 22.","DOI":"10.1186\/s12866-022-02457-6"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"829","DOI":"10.3390\/nu5030829","article-title":"The Role of Gut Microbiota on Insulin Resistance","volume":"5","author":"Caricilli","year":"2013","journal-title":"Nutrients"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1186\/s13048-020-00670-3","article-title":"Role of Gut Microbiota in the Development of Insulin Resistance and the Mechanism Underlying Polycystic Ovary Syndrome: A Review","volume":"13","author":"He","year":"2020","journal-title":"J. Ovarian Res."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Luck, B., Engevik, M.A., Ganesh, B.P., Lackey, E.P., Lin, T., Balderas, M., Major, A., Runge, J., Luna, R.A., and Sillitoe, R.V. (2020). Bifidobacteria Shape Host Neural Circuits during Postnatal Development by Promoting Synapse Formation and Microglial Function. Sci. Rep., 10.","DOI":"10.1038\/s41598-020-64173-3"},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Hu, Y., Peng, J., Li, F., Wong, F.S., and Wen, L. (2018). Evaluation of Different Mucosal Microbiota Leads to Gut Microbiota-Based Prediction of Type 1 Diabetes in NOD Mice. Sci. Rep., 8.","DOI":"10.1038\/s41598-018-33571-z"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1186\/s40001-024-01702-0","article-title":"Dynamic Changes in the Gut Microbiota during Three Consecutive Trimesters of Pregnancy and Their Correlation with Abnormal Glucose and Lipid Metabolism","volume":"29","author":"Gao","year":"2024","journal-title":"Eur. J. Med. Res."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Soderborg, T.K., Carpenter, C.M., Janssen, R.C., Weir, T.L., Robertson, C.E., Ir, D., Young, B.E., Krebs, N.F., Hernandez, T.L., and Barbour, L.A. (2020). Gestational Diabetes Is Uniquely Associated with Altered Early Seeding of the Infant Gut Microbiota. Front. Endocrinol., 11.","DOI":"10.3389\/fendo.2020.603021"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"106520","DOI":"10.1016\/j.envint.2021.106520","article-title":"Contribution of Trace Element Exposure to Gestational Diabetes Mellitus through Disturbing the Gut Microbiome","volume":"153","author":"Zhang","year":"2021","journal-title":"Environ. Int."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Byers, S.L., Wiles, M.V., Dunn, S.L., and Taft, R.A. (2012). Mouse Estrous Cycle Identification Tool and Images. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0035538"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1669","DOI":"10.1016\/j.biopha.2017.09.104","article-title":"Anti-Diabetic Effects of Inonotus Obliquus Polysaccharides in Streptozotocin-Induced Type 2 Diabetic Mice and Potential Mechanism via PI3K-Akt Signal Pathway","volume":"95","author":"Wang","year":"2017","journal-title":"Biomed. Pharmacother."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Nelson, M.C., Morrison, H.G., Benjamino, J., Grim, S.L., and Graf, J. (2014). Analysis, Optimization and Verification of Illumina-Generated 16s RRNA Gene Amplicon Surveys. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0094249"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1038\/nmeth.f.303","article-title":"QIIME Allows Analysis of High-Throughput Community Sequencing Data","volume":"7","author":"Caporaso","year":"2010","journal-title":"Nat. Methods"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"2194","DOI":"10.1093\/bioinformatics\/btr381","article-title":"UCHIME Improves Sensitivity and Speed of Chimera Detection","volume":"27","author":"Edgar","year":"2011","journal-title":"Bioinformatics"},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Honarpisheh, P., Reynolds, C.R., Conesa, M.P.B., Manchon, J.F.M., Putluri, N., Bhattacharjee, M.B., Urayama, A., McCullough, L.D., and Ganesh, B.P. (2020). Dysregulated Gut Homeostasis Observed Prior to the Accumulation of the Brain Amyloid-\u03b2 in Tg2576 Mice. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21051711"},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Ganesh, B.P., Klopfleisch, R., Loh, G., and Blaut, M. (2013). Commensal Akkermansia Muciniphila Exacerbates Gut Inflammation in Salmonella Typhimurium-Infected Gnotobiotic Mice. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0074963"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"191","DOI":"10.3233\/JAD-220106","article-title":"Bacterial Amyloid Curli Associated Gut Epithelial Neuroendocrine Activation Predominantly Observed in Alzheimer\u2019s Disease Mice with Central Amyloid-\u03b2 Pathology","volume":"88","author":"Das","year":"2022","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"e13977","DOI":"10.1111\/acel.13977","article-title":"Iron Overload Induces Cerebral Endothelial Senescence in Aged Mice and in Primary Culture in a Sex-Dependent Manner","volume":"22","author":"Noh","year":"2023","journal-title":"Aging Cell"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1117","DOI":"10.1038\/nprot.2006.170","article-title":"Assessing Nest Building in Mice","volume":"1","author":"Deacon","year":"2006","journal-title":"Nat. Protoc."},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Hollister, E.B., Riehle, K., Luna, R.A., Weidler, E.M., Rubio-Gonzales, M., Mistretta, T.A., Raza, S., Doddapaneni, H.V., Metcalf, G.A., and Muzny, D.M. (2015). Structure and Function of the Healthy Pre-Adolescent Pediatric Gut Microbiome. Microbiome, 3.","DOI":"10.1186\/s40168-015-0101-x"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1002\/ana.25250","article-title":"Age-Related Changes in the Gut Microbiota Influence Systemic Inflammation and Stroke Outcome","volume":"84","author":"Spychala","year":"2018","journal-title":"Ann. Neurol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/7\/3140\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:04:28Z","timestamp":1760029468000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/7\/3140"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,28]]},"references-count":68,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2025,4]]}},"alternative-id":["ijms26073140"],"URL":"https:\/\/doi.org\/10.3390\/ijms26073140","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,28]]}}}