{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T19:31:51Z","timestamp":1789673511453,"version":"4.0.1"},"reference-count":94,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2021,12,9]],"date-time":"2021-12-09T00:00:00Z","timestamp":1639008000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Alfons Geib foundation for dementia research","award":["nn"],"award-info":[{"award-number":["nn"]}]},{"DOI":"10.13039\/501100001645","name":"Boehringer Ingelheim Fonds","doi-asserted-by":"publisher","award":["BIS_04"],"award-info":[{"award-number":["BIS_04"]}],"id":[{"id":"10.13039\/501100001645","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Dr.Georg Scheuing foundation","award":["nn"],"award-info":[{"award-number":["nn"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Microorganisms"],"abstract":"<jats:p>Alzheimer\u2019s disease is a progressive neurodegenerative disorder affecting around 30 million patients worldwide. The predominant sporadic variant remains enigmatic as the underlying cause has still not been identified. Since efficient therapeutic treatments are still lacking, the microbiome and its manipulation have been considered as a new, innovative approach. 5xFAD Alzheimer\u2019s disease model mice were subjected to one-time fecal material transfer after antibiotics-treatment using two types of inoculation: material derived from the caecum of age-matched (young) wild type mice or from middle aged, 1 year old (old) wild type mice. Mice were profiled after transfer for physiological parameters, microbiome, behavioral tasks, and amyloid deposition. A single time transfer of cecal material from the older donor group established an aged phenotype in the recipient animals as indicated by elevated cultivatable fecal Enterobacteriaceae and Lactobacillaceae representative bacteria, a decreased Firmicutes amount as assessed by qPCR, and by increased levels of serum LPS binding protein. While behavioral deficits were not accelerated, single brain regions (prefrontal cortex and dentate gyrus) showed higher plaque load after transfer of material from older animals. We could demonstrate that the age of the donor of cecal material might affect early pathological hallmarks of Alzheimer\u2019s disease. This could be relevant when considering new microbiome-based therapies for this devastating disorder.<\/jats:p>","DOI":"10.3390\/microorganisms9122548","type":"journal-article","created":{"date-parts":[[2021,12,9]],"date-time":"2021-12-09T21:46:58Z","timestamp":1639086418000},"page":"2548","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Impact of the Age of Cecal Material Transfer Donors on Alzheimer\u2019s Disease Pathology in 5xFAD Mice"],"prefix":"10.3390","volume":"9","author":[{"given":"Francesco","family":"Valeri","sequence":"first","affiliation":[{"name":"Department of Psychiatry and Psychotherapy, University Medical Center, Johannes Gutenberg University Mainz, 55131 Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malena","family":"dos Santos Guilherme","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Psychotherapy, University Medical Center, Johannes Gutenberg University Mainz, 55131 Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fuqian","family":"He","sequence":"additional","affiliation":[{"name":"The Center of Gerontology and Geriatrics, West China Hospital of Sichuan University, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolai M.","family":"Stoye","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Psychotherapy, University Medical Center, Johannes Gutenberg University Mainz, 55131 Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2876-2352","authenticated-orcid":false,"given":"Andreas","family":"Schwiertz","sequence":"additional","affiliation":[{"name":"MVZ Institute fuer Mikrooekologie GmbH, 35745 Herborn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1099-8287","authenticated-orcid":false,"given":"Kristina","family":"Endres","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Psychotherapy, University Medical Center, Johannes Gutenberg University Mainz, 55131 Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1159\/000488629","article-title":"Influence of Commensal Microbiota on the Enteric Nervous System and Its Role in Neurodegenerative Diseases","volume":"10","author":"Endres","year":"2018","journal-title":"J. Innate Immun."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"3769","DOI":"10.1007\/s00018-017-2550-9","article-title":"Microbiome, probiotics and neurodegenerative diseases: Deciphering the gut brain axis","volume":"74","author":"Westfall","year":"2017","journal-title":"Cell Mol. Life Sci."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"6152","DOI":"10.2174\/1381612822666160907093807","article-title":"The Gut-Brain Axis, Including the Microbiome, Leaky Gut and Bacterial Translocation: Mechanisms and Pathophysiological Role in Alzheimer\u2019s Disease","volume":"22","author":"Kohler","year":"2016","journal-title":"Curr. Pharm. Des."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1016\/j.jad.2015.09.069","article-title":"The prevalence of neuropsychiatric symptoms in Alzheimer\u2019s disease: Systematic review and meta-analysis","volume":"190","author":"Zhao","year":"2016","journal-title":"J. Affect Disord."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1159\/000486546","article-title":"A Systematic Review and Meta-Analysis of the Effectiveness of Acetylcholinesterase Inhibitors and Memantine in Treating the Cognitive Symptoms of Dementia","volume":"45","author":"Knight","year":"2018","journal-title":"Dement. Geriatr. Cogn. Disord."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"13537","DOI":"10.1038\/s41598-017-13601-y","article-title":"Gut microbiome alterations in Alzheimer\u2019s disease","volume":"7","author":"Vogt","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/j.neurobiolaging.2016.08.019","article-title":"Association of brain amyloidosis with pro-inflammatory gut bacterial taxa and peripheral inflammation markers in cognitively impaired elderly","volume":"49","author":"Cattaneo","year":"2017","journal-title":"Neurobiol. Aging"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"182","DOI":"10.3389\/fnagi.2019.00182","article-title":"The Synthetic Retinoid Acitretin Increases IL-6 in the Central Nervous System of Alzheimer Disease Model Mice and Human Patients","volume":"11","author":"Stoye","year":"2019","journal-title":"Front. Aging Neurosci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"775","DOI":"10.3233\/JAD-160926","article-title":"Altered Gut Microbiome Composition and Tryptic Activity of the 5xFAD Alzheimer\u2019s Mouse Model","volume":"56","author":"Brandscheid","year":"2017","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"405","DOI":"10.2174\/1567205016666190321163705","article-title":"Retinoic Acid and the Gut Microbiota in Alzheimer\u2019s Disease: Fighting Back-to-Back?","volume":"16","author":"Endres","year":"2019","journal-title":"Curr. Alzheimer Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"104706","DOI":"10.18632\/oncotarget.22218","article-title":"Weight loss in the healthy elderly might be a non-cognitive sign of preclinical Alzheimer\u2019s disease","volume":"8","author":"Jimenez","year":"2017","journal-title":"Oncotarget"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1001\/archneur.62.1.55","article-title":"A 32-year prospective study of change in body weight and incident dementia: The Honolulu-Asia Aging Study","volume":"62","author":"Stewart","year":"2005","journal-title":"Arch. Neurol"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1312","DOI":"10.1001\/archneur.63.9.1312","article-title":"Accelerated weight loss may precede diagnosis in Alzheimer disease","volume":"63","author":"Johnson","year":"2006","journal-title":"Arch. Neurol"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1007\/PL00009539","article-title":"Eating changes in mild-stage Alzheimer\u2019s disease: A pilot study","volume":"12","author":"Priefer","year":"1997","journal-title":"Dysphagia"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1136\/jnnp.73.4.371","article-title":"Changes in appetite, food preference, and eating habits in frontotemporal dementia and Alzheimer\u2019s disease","volume":"73","author":"Ikeda","year":"2002","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"98","DOI":"10.3389\/fcimb.2020.00098","article-title":"Fecal Microbiota Transplantation in Neurological Disorders","volume":"10","author":"Vendrik","year":"2020","journal-title":"Front. Cell Infect. Microbiol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1111\/apt.14201","article-title":"Systematic review with meta-analysis: The efficacy of faecal microbiota transplantation for the treatment of recurrent and refractory Clostridium difficile infection","volume":"46","author":"Quraishi","year":"2017","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"102092","DOI":"10.1016\/j.anaerobe.2019.102092","article-title":"Fecal microbiota transplantation (FMT) for C. difficile infection, just say \u2018No\u2019","volume":"60","author":"Tan","year":"2019","journal-title":"Anaerobe"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"10713","DOI":"10.1073\/pnas.1711235114","article-title":"Gut bacteria from multiple sclerosis patients modulate human T cells and exacerbate symptoms in mouse models","volume":"114","author":"Cekanaviciute","year":"2017","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1038\/nrgastro.2011.244","article-title":"Fecal microbiota transplantation and emerging applications","volume":"9","author":"Borody","year":"2011","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1002\/epi4.12114","article-title":"Facilitation of kindling epileptogenesis by chronic stress may be mediated by intestinal microbiome","volume":"3","author":"Shin","year":"2018","journal-title":"Epilepsia Open"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"3565","DOI":"10.3748\/wjg.v23.i19.3565","article-title":"Fecal microbiota transplantation cured epilepsy in a case with Crohn\u2019s disease: The first report","volume":"23","author":"He","year":"2017","journal-title":"World J. Gastroenterol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"41802","DOI":"10.1038\/srep41802","article-title":"Reduction of Abeta amyloid pathology in APPPS1 transgenic mice in the absence of gut microbiota","volume":"7","author":"Harach","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2144","DOI":"10.1080\/09168451.2019.1644149","article-title":"Fecal metabolite of a gnotobiotic mouse transplanted with gut microbiota from a patient with Alzheimer\u2019s disease","volume":"83","author":"Fujii","year":"2019","journal-title":"Biosci. Biotechnol. Biochem."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1038\/s41398-019-0525-3","article-title":"Fecal microbiota transplantation alleviated Alzheimer\u2019s disease-like pathogenesis in APP\/PS1 transgenic mice","volume":"9","author":"Sun","year":"2019","journal-title":"Transl. Psychiatry"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1016\/j.jsbmb.2016.03.012","article-title":"Age, APOE and sex: Triad of risk of Alzheimer\u2019s disease","volume":"160","author":"Riedel","year":"2016","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1016\/j.jns.2007.01.025","article-title":"Morphological substrates of cognitive decline in nonagenarians and centenarians: A new paradigm?","volume":"257","author":"Imhof","year":"2007","journal-title":"J. Neurol. Sci."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1987","DOI":"10.1093\/cercor\/bhu012","article-title":"A Brain-Wide Study of Age-Related Changes in Functional Connectivity","volume":"25","author":"Geerligs","year":"2015","journal-title":"Cereb Cortex"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"(2020). 2020 Alzheimer\u2019s disease facts and figures. Alzheimer\u2019s Dement, 16, 391\u2013462.","DOI":"10.1002\/alz.12068"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1737","DOI":"10.1001\/archneur.59.11.1737","article-title":"Dementia and Alzheimer disease incidence: A prospective cohort study","volume":"59","author":"Kukull","year":"2002","journal-title":"Arch. Neurol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"10129","DOI":"10.1523\/JNEUROSCI.1202-06.2006","article-title":"Intraneuronal beta-amyloid aggregates, neurodegeneration, and neuron loss in transgenic mice with five familial Alzheimer\u2019s disease mutations: Potential factors in amyloid plaque formation","volume":"26","author":"Oakley","year":"2006","journal-title":"J. Neurosci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1329","DOI":"10.1038\/s41598-018-19577-7","article-title":"Identification of disulfiram as a secretase-modulating compound with beneficial effects on Alzheimer\u2019s disease hallmarks","volume":"8","author":"Reinhardt","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"30028","DOI":"10.1038\/srep30028","article-title":"Antibiotic-induced perturbations in gut microbial diversity influences neuro-inflammation and amyloidosis in a murine model of Alzheimer\u2019s disease","volume":"6","author":"Minter","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/0378-3782(87)90039-9","article-title":"Teratology of the antituberculosis drugs","volume":"15","author":"Holdiness","year":"1987","journal-title":"Early Hum. Dev."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"5922","DOI":"10.1038\/srep05922","article-title":"Transfer of gut microbiota from lean and obese mice to antibiotic-treated mice","volume":"4","author":"Ellekilde","year":"2014","journal-title":"Sci. Rep."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2354","DOI":"10.1038\/s41467-020-15545-w","article-title":"Fecal microbiota transplant rescues mice from human pathogen mediated sepsis by restoring systemic immunity","volume":"11","author":"Kim","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1186\/s40168-020-00917-7","article-title":"Spatial heterogeneity of bacterial colonization across different gut segments following inter-species microbiota transplantation","volume":"8","author":"Li","year":"2020","journal-title":"Microbiome"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"e13442","DOI":"10.7554\/eLife.13442","article-title":"Microbiota-driven transcriptional changes in prefrontal cortex override genetic differences in social behavior","volume":"5","author":"Gacias","year":"2016","journal-title":"Elife"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1008","DOI":"10.3389\/fmicb.2020.01008","article-title":"Impact of Acute and Chronic Amyloid-beta Peptide Exposure on Gut Microbial Commensals in the Mouse","volume":"11","author":"Todorov","year":"2020","journal-title":"Front. Microbiol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"6066","DOI":"10.1073\/pnas.0701106104","article-title":"Neural encoding of the concept of nest in the mouse brain","volume":"104","author":"Lin","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_41","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_42","doi-asserted-by":"crossref","first-page":"80","DOI":"10.2174\/1567205017666200217105537","article-title":"Elevated Testosterone Level and Urine Scent Marking in Male 5xFAD Alzheimer Model Mice","volume":"17","author":"Gadomsky","year":"2020","journal-title":"Curr Alzheimer Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1038\/nprot.2006.2","article-title":"T-maze alternation in the rodent","volume":"1","author":"Deacon","year":"2006","journal-title":"Nat. Protoc."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1671","DOI":"10.1038\/nprot.2006.275","article-title":"Two-day radial-arm water maze learning and memory task; robust resolution of amyloid-related memory deficits in transgenic mice","volume":"1","author":"Alamed","year":"2006","journal-title":"Nat. Protoc."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Ly, P.T., Cai, F., and Song, W. (2011). Detection of neuritic plaques in Alzheimer\u2019s disease mouse model. J. Vis. Exp., 2831.","DOI":"10.3791\/2831"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1060","DOI":"10.1093\/gerona\/glt156","article-title":"Aging-associated reductions in lipolytic and mitochondrial proteins in mouse adipose tissue are not rescued by metformin treatment","volume":"69","author":"Mennes","year":"2014","journal-title":"J. Gerontol. A Biol. Sci. Med. Sci."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/S0022-2275(20)39838-2","article-title":"Effect of aging and cellularity on lipolysis in isolated mouse fat cells","volume":"21","author":"Jolly","year":"1980","journal-title":"J. Lipid Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"930","DOI":"10.18632\/aging.101439","article-title":"Integrative analysis of gut microbiota composition, host colonic gene expression and intraluminal metabolites in aging C57BL\/6J mice","volume":"10","author":"Rusli","year":"2018","journal-title":"Aging"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.physbeh.2012.12.018","article-title":"Impact of nesting material on mouse body temperature and physiology","volume":"110\u2013111","author":"Gaskill","year":"2013","journal-title":"Physiol. Behav."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1016\/S1474-4422(12)70291-0","article-title":"Tracking pathophysiological processes in Alzheimer\u2019s disease: An updated hypothetical model of dynamic biomarkers","volume":"12","author":"Jack","year":"2013","journal-title":"Lancet Neurol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"2174","DOI":"10.3389\/fimmu.2019.02174","article-title":"Antibiotic Treatment Protocols and Germ-Free Mouse Models in Vascular Research","volume":"10","author":"Bayer","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1534","DOI":"10.3389\/fphys.2018.01534","article-title":"Mouse Microbiota Models: Comparing Germ-Free Mice and Antibiotics Treatment as Tools for Modifying Gut Bacteria","volume":"9","author":"Kennedy","year":"2018","journal-title":"Front. Physiol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"14184","DOI":"10.1038\/s41598-018-32366-6","article-title":"Commensal microbiota induces colonic barrier structure and functions that contribute to homeostasis","volume":"8","author":"Hayes","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"489","DOI":"10.3389\/fcimb.2017.00489","article-title":"Microbiota Modulate Anxiety-Like Behavior and Endocrine Abnormalities in Hypothalamic-Pituitary-Adrenal Axis","volume":"7","author":"Huo","year":"2017","journal-title":"Front. Cell Infect. Microbiol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"10411","DOI":"10.1038\/s41598-017-11047-w","article-title":"Antibiotic-induced perturbations in microbial diversity during post-natal development alters amyloid pathology in an aged APPSWE\/PS1DeltaE9 murine model of Alzheimer\u2019s disease","volume":"7","author":"Minter","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"2287","DOI":"10.1038\/s41380-018-0086-5","article-title":"Gut microbiota modulate neurobehavior through changes in brain insulin sensitivity and metabolism","volume":"23","author":"Soto","year":"2018","journal-title":"Mol. Psychiatry"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"2872","DOI":"10.1038\/s41467-018-05336-9","article-title":"Antibiotic-induced microbiome depletion alters metabolic homeostasis by affecting gut signaling and colonic metabolism","volume":"9","author":"Zarrinpar","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"2397","DOI":"10.1096\/fj.14-265983","article-title":"Alteration of gut microbiota by vancomycin and bacitracin improves insulin resistance via glucagon-like peptide 1 in diet-induced obesity","volume":"29","author":"Hwang","year":"2015","journal-title":"FASEB J."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Guilherme, M.D.S., Nguyen, V.T.T., Reinhardt, C., and Endres, K. (2021). Impact of Gut Microbiome Manipulation in 5xFAD Mice on Alzheimer\u2019s Disease-Like Pathology. Microorganisms, 9.","DOI":"10.3390\/microorganisms9040815"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"8183","DOI":"10.1038\/s41598-020-64797-5","article-title":"Synergistic depletion of gut microbial consortia, but not individual antibiotics, reduces amyloidosis in APPPS1-21 Alzheimer\u2019s transgenic mice","volume":"10","author":"Dodiya","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"113156","DOI":"10.1016\/j.bbr.2021.113156","article-title":"Maternal antibiotic administration during a critical developmental window has enduring neurobehavioural effects in offspring mice","volume":"404","author":"Moloney","year":"2021","journal-title":"Behav Brain Res."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Tochitani, S., Ikeno, T., Ito, T., Sakurai, A., Yamauchi, T., and Matsuzaki, H. (2016). Administration of Non-Absorbable Antibiotics to Pregnant Mice to Perturb the Maternal Gut Microbiota Is Associated with Alterations in Offspring Behavior. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0138293"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1017\/S0007114509991553","article-title":"The effect of age and non-steroidal anti-inflammatory drugs on human intestinal microbiota composition","volume":"103","author":"Makivuokko","year":"2010","journal-title":"Br. J. Nutr."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1016\/j.chom.2008.05.010","article-title":"Commensals, bacterial pathogens and intestinal inflammation: An intriguing menage a trois","volume":"3","author":"Pedron","year":"2008","journal-title":"Cell Host Microbe"},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Biagi, E., Nylund, L., Candela, M., Ostan, R., Bucci, L., Pini, E., Nikkila, J., Monti, D., Satokari, R., and Franceschi, C. (2010). Through ageing, and beyond: Gut microbiota and inflammatory status in seniors and centenarians. PLoS ONE, 5.","DOI":"10.1371\/annotation\/df45912f-d15c-44ab-8312-e7ec0607604d"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"4985","DOI":"10.1128\/AEM.00753-08","article-title":"Ecological role of lactobacilli in the gastrointestinal tract: Implications for fundamental and biomedical research","volume":"74","author":"Walter","year":"2008","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Poutahidis, T., Springer, A., Levkovich, T., Qi, P., Varian, B.J., Lakritz, J.R., Ibrahim, Y.M., Chatzigiagkos, A., Alm, E.J., and Erdman, S.E. (2014). Probiotic microbes sustain youthful serum testosterone levels and testicular size in aging mice. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0084877"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1089\/jmf.2018.4229","article-title":"Lactobacillus Strains Alleviated Aging Symptoms and Aging-Induced Metabolic Disorders in Aged Rats","volume":"22","author":"Hor","year":"2019","journal-title":"J. Med. Food"},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Mariat, D., Firmesse, O., Levenez, F., Guimaraes, V., Sokol, H., Dore, J., Corthier, G., and Furet, J.P. (2009). The Firmicutes\/Bacteroidetes ratio of the human microbiota changes with age. BMC Microbiol., 9.","DOI":"10.1186\/1471-2180-9-123"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"6330","DOI":"10.18632\/aging.202525","article-title":"Age-dependent remodeling of gut microbiome and host serum metabolome in mice","volume":"13","author":"Wu","year":"2021","journal-title":"Aging"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1136\/gut.48.2.198","article-title":"Age and disease related changes in intestinal bacterial populations assessed by cell culture, 16S rRNA abundance, and community cellular fatty acid profiles","volume":"48","author":"Hopkins","year":"2001","journal-title":"Gut"},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Odamaki, T., Kato, K., Sugahara, H., Hashikura, N., Takahashi, S., Xiao, J.Z., Abe, F., and Osawa, R. (2016). Age-related changes in gut microbiota composition from newborn to centenarian: A cross-sectional study. BMC Microbiol., 16.","DOI":"10.1186\/s12866-016-0708-5"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1450","DOI":"10.1080\/19490976.2020.1763770","article-title":"Gut microbiota remodeling reverses aging-associated inflammation and dysregulation of systemic bile acid homeostasis in mice sex-specifically","volume":"11","author":"Ma","year":"2020","journal-title":"Gut Microbes"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"2608","DOI":"10.1016\/j.celrep.2017.02.056","article-title":"Canonical Wnt Signaling Ameliorates Aging of Intestinal Stem Cells","volume":"18","author":"Nalapareddy","year":"2017","journal-title":"Cell Rep."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/S0047-6374(98)00142-0","article-title":"Age-induced changes in the enteric nervous system in the mouse","volume":"107","author":"Sandstrom","year":"1999","journal-title":"Mech. Ageing Dev."},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Gonzalez-Quintela, A., Alonso, M., Campos, J., Vizcaino, L., Loidi, L., and Gude, F. (2013). Determinants of serum concentrations of lipopolysaccharide-binding protein (LBP) in the adult population: The role of obesity. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0054600"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1016\/j.chom.2017.03.002","article-title":"Age-Associated Microbial Dysbiosis Promotes Intestinal Permeability, Systemic Inflammation, and Macrophage Dysfunction","volume":"21","author":"Thevaranjan","year":"2017","journal-title":"Cell Host Microbe"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"R99","DOI":"10.1152\/ajpregu.00557.2006","article-title":"Thermoregulation and aging","volume":"292","year":"2007","journal-title":"Am. J. Physiol. Regul. Integr. Comp. Physiol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1007\/s11357-009-9109-0","article-title":"Thermoregulation in mice exhibits genetic variability early in senescence","volume":"32","author":"Gonzales","year":"2010","journal-title":"Age"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/S0166-4328(01)00401-6","article-title":"Hippocampal cytotoxic lesion effects on species-typical behaviours in mice","volume":"132","author":"Deacon","year":"2002","journal-title":"Behav. Brain Res."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1037\/h0038350","article-title":"Nest building, general activity, and salt preference of rats following hippocampal ablation","volume":"53","author":"Kim","year":"1960","journal-title":"J. Comp. Physiol. Psychol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1023\/A:1025610130282","article-title":"Nesting and fitness: Lifetime reproductive success in house mice bidirectionally selected for thermoregulatory nest-building behavior","volume":"27","author":"Bult","year":"1997","journal-title":"Behav. Genet."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.physbeh.2014.05.041","article-title":"Behavioral and EEG changes in male 5xFAD mice","volume":"135","author":"Schneider","year":"2014","journal-title":"Physiol. Behav."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1097\/nen.0b013e318160c5db","article-title":"Failure of neuronal maturation in Alzheimer disease dentate gyrus","volume":"67","author":"Li","year":"2008","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1403","DOI":"10.1001\/archneur.58.9.1403","article-title":"Selective preservation and degeneration within the prefrontal cortex in aging and Alzheimer disease","volume":"58","author":"Salat","year":"2001","journal-title":"Arch. Neurol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1232","DOI":"10.1093\/gerona\/glz262","article-title":"Gut Microbiota: From the Forgotten Organ to a Potential Key Player in the Pathology of Alzheimer\u2019s Disease","volume":"75","author":"Seo","year":"2020","journal-title":"J. Gerontol. A Biol. Sci. Med. Sci."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1186\/s42826-019-0018-9","article-title":"Lipopolysaccharide induces neuroglia activation and NF-kappaB activation in cerebral cortex of adult mice","volume":"35","author":"Kang","year":"2019","journal-title":"Lab. Anim. Res."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"4930","DOI":"10.1523\/JNEUROSCI.5480-05.2006","article-title":"Induction of glial fibrillary acidic protein expression in astrocytes by nitric oxide","volume":"26","author":"Brahmachari","year":"2006","journal-title":"J. Neurosci."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"2889","DOI":"10.1016\/j.celrep.2016.08.028","article-title":"Aging Triggers a Repressive Chromatin State at Bdnf Promoters in Hippocampal Neurons","volume":"16","author":"Palomer","year":"2016","journal-title":"Cell Rep."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/S0165-3806(02)00540-0","article-title":"BDNF mRNA expression during postnatal development, maturation and aging of the human prefrontal cortex","volume":"139","author":"Webster","year":"2002","journal-title":"Brain Res. Dev. Brain Res."},{"key":"ref_91","doi-asserted-by":"crossref","unstructured":"Ng, T.K.S., Ho, C.S.H., Tam, W.W.S., Kua, E.H., and Ho, R.C. (2019). Decreased Serum Brain-Derived Neurotrophic Factor (BDNF) Levels in Patients with Alzheimer\u2019s Disease (AD): A Systematic Review and Meta-Analysis. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20020257"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1031","DOI":"10.1089\/rej.2008.0791","article-title":"Effect of aging on brain-derived neurotrophic factor, proBDNF, and their receptors in the hippocampus of Lou\/C rats","volume":"11","author":"Silhol","year":"2008","journal-title":"Rejuvenation Res."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/j.brainresrev.2008.07.007","article-title":"New insights into brain BDNF function in normal aging and Alzheimer disease","volume":"59","author":"Aliaga","year":"2008","journal-title":"Brain Res. Rev."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"1217","DOI":"10.1007\/s00702-005-0397-y","article-title":"Stage-dependent BDNF serum concentrations in Alzheimer\u2019s disease","volume":"113","author":"Laske","year":"2006","journal-title":"J. Neural. Transm."}],"container-title":["Microorganisms"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-2607\/9\/12\/2548\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:44:27Z","timestamp":1760168667000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-2607\/9\/12\/2548"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,12,9]]},"references-count":94,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["microorganisms9122548"],"URL":"https:\/\/doi.org\/10.3390\/microorganisms9122548","relation":{},"ISSN":["2076-2607"],"issn-type":[{"value":"2076-2607","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,12,9]]}}}