{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T20:14:43Z","timestamp":1791317683402,"version":"4.3.1"},"reference-count":104,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,6,30]],"date-time":"2025-06-30T00:00:00Z","timestamp":1751241600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004504","name":"Research Council of Lithuania","doi-asserted-by":"publisher","award":["S-PD-24-95"],"award-info":[{"award-number":["S-PD-24-95"]}],"id":[{"id":"10.13039\/501100004504","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Aging Neurosci."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Bidirectional communication and mutual regulation between the gastrointestinal tract and the CNS is facilitated through the gut-brain axis. Recent studies have found reduced diversity of the gut microbiota in Alzheimer\u2019s disease (AD) patients, and animal models suggest microbial involvement in amyloid beta peptide (A\u03b2) accumulation. Modulation of the gut microbiota by new-generation probiotics represents a novel treatment strategy to alleviate the symptoms and slow the progression of AD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      In this study, the therapeutic effect of the probiotic\n                      <jats:italic>Akkermansia muciniphila<\/jats:italic>\n                      and the prebiotic galactooligosaccharides (GOS) was investigated in the APP\/PS1 mouse model. After 7\u202fmonths of triweekly administration, we evaluated physiological parameters, glucose metabolism, and behavioral outcomes. Additionally, we assessed gut microbiota diversity and composition, short-chain fatty acid (SCFA) concentrations in the cecum, A\u03b2 load in the hippocampus and prefrontal cortex, and microglial abundance in the hippocampus.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      <jats:italic>A. muciniphila<\/jats:italic>\n                      and GOS administration normalized fasting glucose levels, glucose metabolism, and intestinal transit time to wild-type levels. Furthermore, supplementation reduced anxiety, improved long-and short-term memory, and partially restored activity levels. It also regulated SCFA concentrations in the cecum, improved the richness of the gut microbiota, and normalized abundance of microglia in the hippocampus, indicating reduced neuroinflammation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      These findings suggest that long-term administration of\n                      <jats:italic>A. muciniphila<\/jats:italic>\n                      and GOS effectively improves metabolic health and modulates symptoms of AD in the APP\/PS1 mouse model.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fnagi.2025.1617980","type":"journal-article","created":{"date-parts":[[2025,6,30]],"date-time":"2025-06-30T01:26:15Z","timestamp":1751246775000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":16,"title":["Intermittent supplementation with Akkermansia muciniphila and galactooligosaccharides modulates Alzheimer\u2019s disease progression, gut microbiota, and colon short-chain fatty acid profiles in mice"],"prefix":"10.3389","volume":"17","author":[{"given":"Arnas","family":"Kunevi\u010dius","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akshay Kumar","family":"Vijaya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Atzeni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonas","family":"Mingaila","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ieva","family":"\u0160imoli\u016bn\u0117","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rapolas","family":"Jamontas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emilija","family":"Ke\u017eevi\u010di\u016bt\u0117","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miguel","family":"Gueimonde","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rolandas","family":"Me\u0161kys","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daiva","family":"Baltriukien\u0117","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Arboleya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aurelijus","family":"Burokas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,6,30]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"271","DOI":"10.1023\/A:1007529726302","article-title":"Logratio analysis and compositional distance","volume":"32","author":"Aitchison","year":"2000","journal-title":"Math. Geol."},{"key":"ref2","doi-asserted-by":"publisher","first-page":"256","DOI":"10.3389\/fnagi.2016.00256","article-title":"Effect of probiotic supplementation on cognitive function and metabolic status in Alzheimer\u2019s disease: a randomized, double-blind and controlled trial","volume":"8","author":"Akbari","year":"2016","journal-title":"Front. Aging Neurosci."},{"key":"ref3","doi-asserted-by":"publisher","first-page":"505","DOI":"10.1007\/s11033-024-09398-5","article-title":"Next-generation probiotics: the upcoming biotherapeutics","volume":"51","author":"Al-Fakhrany","year":"2024","journal-title":"Mol. Biol. Rep."},{"key":"ref4","doi-asserted-by":"publisher","first-page":"1783","DOI":"10.1080\/10408398.2019.1599812","article-title":"Evolving trends in next-generation probiotics: a 5W1H perspective","volume":"60","author":"Almeida","year":"2020","journal-title":"Crit. Rev. Food Sci. Nutr."},{"key":"ref5","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1111\/j.1442-9993.2001.01070.pp.x","article-title":"A new method for non-parametric multivariate analysis of variance","volume":"26","author":"Anderson","year":"2001","journal-title":"Austral Ecol."},{"key":"ref6","doi-asserted-by":"publisher","first-page":"e50978","DOI":"10.3791\/50978","article-title":"Marble burying and Nestlet shredding as tests of repetitive, compulsive-like behaviors in mice","volume":"24","author":"Angoa-P\u00e9rez","year":"2013","journal-title":"J. Vis. Exp."},{"key":"ref7","doi-asserted-by":"publisher","first-page":"548","DOI":"10.1016\/j.cmet.2020.09.002","article-title":"Obesity impairs short-term and working memory through gut microbial metabolism of aromatic amino acids","volume":"32","author":"Arnoriaga-Rodr\u00edguez","year":"2020","journal-title":"Cell Metab."},{"key":"ref8","article-title":"Anxiety-related behaviors in mice","volume-title":"Methods of behavior analysis in neuroscience","author":"Bailey","year":"2009"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"737","DOI":"10.1021\/cn5003539","article-title":"Dihydroquinoline carbamate derivatives as \u201cbio-oxidizable\u201d prodrugs for brain delivery of acetylcholinesterase inhibitors: [11C] Radiosynthesis and biological evaluation","volume":"6","author":"Bohn","year":"2015","journal-title":"ACS Chem. Neurosci."},{"key":"ref10","doi-asserted-by":"publisher","first-page":"9884","DOI":"10.1038\/s41598-020-65908-y","article-title":"High fat diet worsens Alzheimer\u2019s disease-related behavioral abnormalities and neuropathology in APP\/PS1 mice, but not by synergistically decreasing cerebral blood flow","volume":"10","author":"Bracko","year":"2020","journal-title":"Sci. Rep."},{"key":"ref11","doi-asserted-by":"publisher","first-page":"3384","DOI":"10.3390\/nu14163384","article-title":"The effect of short-term consumption of lactic acid bacteria on the gut microbiota in obese people","volume":"14","author":"Burakova","year":"2022","journal-title":"Nutrients"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"472","DOI":"10.1016\/j.biopsych.2016.12.031","article-title":"Targeting the microbiota-gut-brain axis: prebiotics have anxiolytic and antidepressant-like effects and reverse the impact of chronic stress in mice","volume":"82","author":"Burokas","year":"2017","journal-title":"Biol. Psychiatry"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"544","DOI":"10.1111\/adb.12597","article-title":"Extinction and reinstatement of an operant responding maintained by food in different models of obesity","volume":"23","author":"Burokas","year":"2018","journal-title":"Addict. Biol."},{"key":"ref14","doi-asserted-by":"publisher","first-page":"126","DOI":"10.1111\/jnc.12716","article-title":"Relationships between serotonergic and cannabinoid system in depressive-like behavior: a PET study with [11C]-DASB","volume":"130","author":"Burokas","year":"2014","journal-title":"J. Neurochem."},{"key":"ref15","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/bs.aambs.2015.02.001","article-title":"Microbiota regulation of the mammalian gut-brain axis","volume":"91","author":"Burokas","year":"2015","journal-title":"Adv. Appl. Microbiol."},{"key":"ref16","doi-asserted-by":"publisher","first-page":"479","DOI":"10.1016\/j.biopsych.2011.04.022","article-title":"Differential role of anandamide and 2-arachidonoylglycerol in memory and anxiety-like responses","volume":"70","author":"Busquets-Garcia","year":"2011","journal-title":"Biol. Psychiatry"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"1198291","DOI":"10.3389\/fnins.2023.1198291","article-title":"Editorial: gut microbiota as a therapeutic target in neuropsychiatric disorders: current status and future directions","volume":"17","author":"Cai","year":"2023","journal-title":"Front. Neurosci."},{"key":"ref18","doi-asserted-by":"publisher","first-page":"22996","DOI":"10.1038\/s41598-021-02040-5","article-title":"Effect of N-methyl-d-aspartate receptor enhancing agents on cognition in dementia: an exploratory systematic review and meta-analysis of randomized controlled trials","volume":"11","author":"Chang","year":"2021","journal-title":"Sci. Rep."},{"key":"ref19","doi-asserted-by":"publisher","first-page":"783","DOI":"10.2307\/2531532","article-title":"Estimating the population size for capture-recapture data with unequal catchability","volume":"43","author":"Chao","year":"1987","journal-title":"Biometrics"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"e59826","DOI":"10.7554\/eLife.59826","article-title":"Microbiota-derived short chain fatty acids modulate microglia and promote a\u03b2 plaque deposition","volume":"10","author":"Colombo","year":"2021","journal-title":"eLife"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"1877","DOI":"10.1152\/physrev.00018.2018","article-title":"The microbiota-gut-brain Axis","volume":"99","author":"Cryan","year":"2019","journal-title":"Physiol. Rev."},{"key":"ref22","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1007\/s40259-023-00633-2","article-title":"Anti-amyloid monoclonal antibodies for the treatment of Alzheimer\u2019s disease","volume":"38","author":"Cummings","year":"2024","journal-title":"Bio Drugs"},{"key":"ref23","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1080\/19490976.2015.1035855","article-title":"Autism spectrum disorders and intestinal microbiota","volume":"6","author":"De Angelis","year":"2015","journal-title":"Gut Microbes"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"965","DOI":"10.1038\/nn.4030","article-title":"Host microbiota constantly control maturation and function of microglia in the CNS","volume":"18","author":"Erny","year":"2015","journal-title":"Nat. Neurosci."},{"key":"ref25","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1186\/s40168-016-0189-7","article-title":"Cardiorespiratory fitness as a predictor of intestinal microbial diversity and distinct metagenomic functions","volume":"4","author":"Estaki","year":"2016","journal-title":"Microbiome"},{"key":"ref26","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1016\/j.bbr.2012.12.055","article-title":"Longitudinal behavioral changes in the APP\/PS1 transgenic Alzheimer\u2019s disease model","volume":"242","author":"Ferguson","year":"2013","journal-title":"Behav. Brain Res."},{"key":"ref27","doi-asserted-by":"publisher","first-page":"91","DOI":"10.3233\/JAD-190120","article-title":"Sodium butyrate reduces brain amyloid-\u03b2 levels and improves cognitive memory performance in an Alzheimer\u2019s disease transgenic mouse model at an early disease stage","volume":"74","author":"Fernando","year":"2020","journal-title":"J. Alzheimers Dis."},{"key":"ref28","doi-asserted-by":"publisher","first-page":"2562","DOI":"10.1039\/C6MB00233A","article-title":"NMR analysis of the human saliva metabolome distinguishes dementia patients from matched controls","volume":"12","author":"Figueira","year":"2016","journal-title":"Mol. BioSyst."},{"key":"ref29","doi-asserted-by":"publisher","first-page":"5202","DOI":"10.3390\/ijms23095202","article-title":"Obesity as a risk factor for dementia and Alzheimer\u2019s disease: the role of leptin","volume":"23","author":"Flores-Cordero","year":"2022","journal-title":"Int. J. Mol. Sci."},{"key":"ref30","doi-asserted-by":"publisher","first-page":"166","DOI":"10.1016\/j.ebiom.2017.09.020","article-title":"Microbiota-related changes in bile acid & tryptophan metabolism are associated with gastrointestinal dysfunction in a mouse model of autism","volume":"24","author":"Golubeva","year":"2017","journal-title":"EBioMedicine"},{"key":"ref31","doi-asserted-by":"publisher","first-page":"629","DOI":"10.3233\/JAD-180297","article-title":"Metabolic syndrome and amyloid accumulation in the aging brain","volume":"65","author":"Gomez","year":"2018","journal-title":"J. Alzheimers Dis."},{"key":"ref32","doi-asserted-by":"publisher","first-page":"821","DOI":"10.1007\/s12035-023-03602-6","article-title":"Akkermansia muciniphila improves depressive-like symptoms by modulating the level of 5-HT neurotransmitters in the gut and brain of mice","volume":"61","author":"Guo","year":"2024","journal-title":"Mol. Neurobiol."},{"key":"ref33","doi-asserted-by":"publisher","first-page":"383","DOI":"10.1016\/0165-6147(91)90609-V","article-title":"Amyloid deposition as the central event in the aetiology of Alzheimer\u2019s disease","volume":"12","author":"Hardy","year":"1991","journal-title":"Trends Pharmacol. Sci."},{"key":"ref34","doi-asserted-by":"publisher","first-page":"3289","DOI":"10.1128\/JB.01780-14","article-title":"Functional metabolic map of Faecalibacterium prausnitzii, a beneficial human gut microbe","volume":"196","author":"Heinken","year":"2014","journal-title":"J. Bacteriol."},{"key":"ref35","doi-asserted-by":"publisher","first-page":"321","DOI":"10.1038\/s41577-024-01104-7","article-title":"Neuroinflammation in Alzheimer disease","volume":"25","author":"Heneka","year":"2024","journal-title":"Nat. Rev. Immunol."},{"key":"ref36","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1080\/19490976.2021.1880240","article-title":"Akkermansia muciniphila and environmental enrichment reverse cognitive impairment associated with high-fat high-cholesterol consumption in rats","volume":"13","author":"Higarza","year":"2021","journal-title":"Gut Microbes"},{"key":"ref001","doi-asserted-by":"publisher","first-page":"1765","DOI":"10.3233\/JAD-200098","article-title":"Microglia demonstrate local mixed inflammation and a defined morphological shift in an APP\/PS1 mouse model","volume":"77","author":"Holloway","year":"2020","journal-title":"Journal of Alzheimer\u2019s Disease"},{"key":"ref37","doi-asserted-by":"publisher","first-page":"303","DOI":"10.1007\/s11357-016-9929-7","article-title":"Characterization of AD-like phenotype in aged APPSwe\/PS1dE9 mice","volume":"38","author":"Huang","year":"2016","journal-title":"Age"},{"key":"ref38","doi-asserted-by":"publisher","first-page":"e35980","DOI":"10.1016\/j.heliyon.2024.e35980","article-title":"Next generation probiotics for human health: an emerging perspective","volume":"10","author":"Jan","year":"2024","journal-title":"Heliyon"},{"key":"ref39","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3233\/JAD-161141","article-title":"The gut microbiota and Alzheimer\u2019s disease","volume":"58","author":"Jiang","year":"2017","journal-title":"J. Alzheimers Dis."},{"key":"ref40","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1186\/s40168-024-01924-8","article-title":"Akkermansia muciniphila improve cognitive dysfunction by regulating BDNF and serotonin pathway in gut-liver-brain axis","volume":"12","author":"Kang","year":"2024","journal-title":"Microbiome"},{"key":"ref41","doi-asserted-by":"publisher","first-page":"283","DOI":"10.1016\/j.jare.2023.12.010","article-title":"Slow gut transit increases the risk of Alzheimer\u2019s disease: an integrated study of the bi-national cohort in South Korea and Japan and Alzheimer\u2019s disease model mice","volume":"65","author":"Kang","year":"2024","journal-title":"J. Adv. Res."},{"key":"ref42","doi-asserted-by":"publisher","first-page":"1627","DOI":"10.3390\/microorganisms12081627","article-title":"The role of Akkermansia muciniphila on improving gut and metabolic health modulation: a Meta-analysis of preclinical mouse model studies","volume":"12","author":"Khalili","year":"2024","journal-title":"Microorganisms"},{"key":"ref43","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1080\/19490976.2021.1892441","article-title":"Mucin degrader Akkermansia muciniphila accelerates intestinal stem cell-mediated epithelial development","volume":"13","author":"Kim","year":"2021","journal-title":"Gut Microbes"},{"key":"ref44","doi-asserted-by":"publisher","first-page":"575","DOI":"10.1016\/j.trci.2018.06.014","article-title":"Inflammation as a central mechanism in Alzheimer\u2019s disease","volume":"4","author":"Kinney","year":"2018","journal-title":"Alzheimers Dement."},{"key":"ref45","doi-asserted-by":"publisher","first-page":"1","DOI":"10.9758\/cpn.2017.15.1.1","article-title":"Mechanisms of Alzheimer\u2019s disease pathogenesis and prevention: the brain, neural pathology, N-methyl-D-aspartate receptors, tau protein and other risk factors","volume":"15","author":"Kocahan","year":"2017","journal-title":"Clin. Psychopharmacol. Neurosci."},{"key":"ref46","doi-asserted-by":"publisher","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":"ref47","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1016\/j.physbeh.2014.05.006","article-title":"Assessment of mouse anxiety-like behavior in the light-dark box and open-field arena: role of equipment and procedure","volume":"133","author":"Kulesskaya","year":"2014","journal-title":"Physiol. Behav."},{"key":"ref48","doi-asserted-by":"publisher","first-page":"259","DOI":"10.1016\/bs.irn.2022.02.005","article-title":"Is essential tremor a disorder primarily due to GABA dysfunction?","volume":"163","author":"Kuo","year":"2022","journal-title":"Int. Rev. Neurobiol."},{"key":"ref49","doi-asserted-by":"publisher","first-page":"101","DOI":"10.3233\/JAD-220046","article-title":"Safety and efficacy of monoclonal antibodies for Alzheimer\u2019s disease: a systematic review and Meta-analysis of published and unpublished clinical trials","volume":"87","author":"Lacorte","year":"2022","journal-title":"J. Alzheimers Dis."},{"key":"ref50","doi-asserted-by":"publisher","first-page":"430","DOI":"10.3389\/fncel.2019.00430","article-title":"Loss of IL-10 promotes differentiation of microglia to a M1 phenotype","volume":"13","author":"Laffer","year":"2019","journal-title":"Front. Cell. Neurosci."},{"key":"ref51","doi-asserted-by":"publisher","first-page":"439","DOI":"10.1177\/070674370404900705","article-title":"GABAergic function in Alzheimer\u2019s disease: evidence for dysfunction and potential as a therapeutic target for the treatment of behavioural and psychological symptoms of dementia","volume":"49","author":"Lanct\u00f4t","year":"2004","journal-title":"Can. J. Psychiatr."},{"key":"ref52","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1186\/s12974-024-03136-1","article-title":"Hyperglycemia enhances brain susceptibility to lipopolysaccharide-induced neuroinflammation via astrocyte reprogramming","volume":"21","author":"Lee","year":"2024","journal-title":"J. Neuroinflammation"},{"key":"ref53","doi-asserted-by":"publisher","first-page":"1357","DOI":"10.1016\/j.jalz.2019.07.002","article-title":"Mild cognitive impairment has similar alterations as Alzheimer\u2019s disease in gut microbiota","volume":"15","author":"Li","year":"2019","journal-title":"Alzheimers Dement."},{"key":"ref54","doi-asserted-by":"publisher","first-page":"1354447","DOI":"10.3389\/fmicb.2024.1354447","article-title":"Function and therapeutic prospects of next-generation probiotic Akkermansia muciniphila in infectious diseases","volume":"15","author":"Li","year":"2024","journal-title":"Front. Microbiol."},{"key":"ref55","doi-asserted-by":"publisher","first-page":"440","DOI":"10.3390\/foods12030440","article-title":"Analysis of Akkermansia muciniphila in mulberry galacto-oligosaccharide medium via comparative transcriptomics","volume":"12","author":"Li","year":"2023","journal-title":"Foods"},{"key":"ref56","doi-asserted-by":"publisher","first-page":"554","DOI":"10.3389\/fimmu.2015.00554","article-title":"Redirection of epithelial immune responses by short-chain fatty acids through inhibition of histone deacetylases","volume":"6","author":"Lin","year":"2015","journal-title":"Front. Immunol."},{"key":"ref57","doi-asserted-by":"publisher","first-page":"666039","DOI":"10.3389\/fmicb.2021.666039","article-title":"An oligosaccharide rich diet increases Akkermansia spp. bacteria in the equine microbiota","volume":"12","author":"Lindenberg","year":"2021","journal-title":"Front. Microbiol."},{"key":"ref58","doi-asserted-by":"publisher","first-page":"477","DOI":"10.1146\/annurev-pharmtox-010919-023628","article-title":"Microbiota-gut-brain axis: new therapeutic opportunities","volume":"60","author":"Long-Smith","year":"2020","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"ref59","doi-asserted-by":"publisher","first-page":"319","DOI":"10.1097\/NEN.0000000000000176","article-title":"Neuroinflammatory signals in Alzheimer disease and APP\/PS1 transgenic mice: correlations with plaques, tangles, and oligomeric species","volume":"74","author":"L\u00f3pez-Gonz\u00e1lez","year":"2015","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref60","doi-asserted-by":"publisher","first-page":"e3393","DOI":"10.21769\/BioProtoc.3393","article-title":"Use of the Vsoc-maze to study sociability and preference for social novelty in rodents","volume":"9","author":"Mart\u00ednez-Torres","year":"2019","journal-title":"Bio Protoc."},{"key":"ref61","doi-asserted-by":"publisher","first-page":"108352","DOI":"10.1016\/j.neuropharm.2020.108352","article-title":"Efficacy of acetylcholinesterase inhibitors in Alzheimer\u2019s disease","volume":"190","author":"Marucci","year":"2021","journal-title":"Neuropharmacology"},{"key":"ref62","doi-asserted-by":"publisher","first-page":"37","DOI":"10.3390\/nu13010037","article-title":"The microbiota-gut-brain axis and Alzheimer\u2019s disease: neuroinflammation is to blame?","volume":"13","author":"Megur","year":"2020","journal-title":"Nutrients"},{"key":"ref63","doi-asserted-by":"publisher","first-page":"1213370","DOI":"10.3389\/fmicb.2023.1213370","article-title":"In vitro screening and characterization of lactic acid bacteria from Lithuanian fermented food with potential probiotic properties","volume":"14","author":"Megur","year":"2023","journal-title":"Front. Microbiol."},{"key":"ref64","doi-asserted-by":"publisher","first-page":"1201982","DOI":"10.3389\/fnagi.2023.1201982","article-title":"Microglia in Alzheimer\u2019s disease: pathogenesis, mechanisms, and therapeutic potentials","volume":"15","author":"Miao","year":"2023","journal-title":"Front. Aging Neurosci."},{"key":"ref65","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1016\/j.bbi.2014.04.001","article-title":"Obesity and neuroinflammation: a pathway to cognitive impairment","volume":"42","author":"Miller","year":"2014","journal-title":"Brain Behav. Immun."},{"key":"ref66","doi-asserted-by":"publisher","first-page":"12005","DOI":"10.3390\/ijms241512005","article-title":"A comparison of methods of gut microbiota transplantation for preclinical studies","volume":"24","author":"Mingaila","year":"2023","journal-title":"Int. J. Mol. Sci."},{"key":"ref67","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1186\/1471-2288-14-75","article-title":"Tuning multiple imputation by predictive mean matching and local residual draws","volume":"14","author":"Morris","year":"2014","journal-title":"BMC Med. Res. Methodol."},{"key":"ref68","doi-asserted-by":"publisher","first-page":"10609","DOI":"10.3748\/wjg.v21.i37.10609","article-title":"Brain-gut-microbiota axis in Parkinson\u2019s disease","volume":"21","author":"Mulak","year":"2015","journal-title":"World J. Gastroenterol."},{"key":"ref69","doi-asserted-by":"publisher","first-page":"311","DOI":"10.3233\/JAD-2010-1221","article-title":"Alzheimer\u2019s disease and the \u03b2-amyloid peptide","volume":"19","author":"Murphy","year":"2010","journal-title":"J. Alzheimers Dis."},{"key":"ref70","doi-asserted-by":"publisher","first-page":"1155","DOI":"10.1111\/nmo.12378","article-title":"Correlation between the human fecal microbiota and depression","volume":"26","author":"Naseribafrouei","year":"2014","journal-title":"Neurogastroenterol. Motil."},{"key":"ref71","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1038\/s41387-020-0115-8","article-title":"Protective effects of Akkermansia muciniphila on cognitive deficits and amyloid pathology in a mouse model of Alzheimer\u2019s disease","volume":"10","author":"Ou","year":"2020","journal-title":"Nutr. Diabetes"},{"key":"ref72","doi-asserted-by":"publisher","first-page":"13574","DOI":"10.3390\/ijms232113574","article-title":"Modulation of the gut microbiota in memory impairment and Alzheimer\u2019s disease via the inhibition of the parasympathetic nervous system","volume":"23","author":"Park","year":"2022","journal-title":"Int. J. Mol. Sci."},{"key":"ref73","doi-asserted-by":"publisher","first-page":"113805","DOI":"10.1016\/j.expneurol.2021.113805","article-title":"Altered corticostriatal synchronization associated with compulsive-like behavior in APP\/PS1 mice","volume":"344","author":"Peng","year":"2021","journal-title":"Exp. Neurol."},{"key":"ref74","doi-asserted-by":"publisher","first-page":"1589","DOI":"10.1038\/s41598-024-84780-8","article-title":"Protection of Alzheimer\u2019s disease progression by a human-origin probiotics cocktail","volume":"15","author":"Prajapati","year":"2025","journal-title":"Sci. Rep."},{"key":"ref75","doi-asserted-by":"publisher","first-page":"101317","DOI":"10.1016\/j.arr.2021.101317","article-title":"Inflammatory pathways in Alzheimer\u2019s disease mediated by gut microbiota","volume":"68","author":"Qian","year":"2021","journal-title":"Ageing Res. Rev."},{"key":"ref76","doi-asserted-by":"publisher","first-page":"2453","DOI":"10.1038\/s41598-022-06414-1","article-title":"The anti-inflammatory effects of Akkermansia muciniphila and its derivates in HFD\/CCL4-induced murine model of liver injury","volume":"12","author":"Raftar","year":"2022","journal-title":"Sci. Rep."},{"key":"ref77","doi-asserted-by":"crossref","DOI":"10.1002\/9780470316696","volume-title":"Multiple imputation for nonresponse in surveys","author":"Rubin","year":"1987"},{"key":"ref78","doi-asserted-by":"publisher","first-page":"1799","DOI":"10.1136\/gutjnl-2023-331445","article-title":"Gut microbiota signatures of vulnerability to food addiction in mice and humans","volume":"73","author":"Samul\u0117nait\u0117","year":"2024","journal-title":"Gut"},{"key":"ref79","doi-asserted-by":"publisher","first-page":"2473","DOI":"10.15252\/embj.201797397","article-title":"APP mouse models for Alzheimer\u2019s disease preclinical studies","volume":"36","author":"Sasaguri","year":"2017","journal-title":"EMBO J."},{"key":"ref80","doi-asserted-by":"publisher","first-page":"425","DOI":"10.1016\/0167-9473(95)00057-7","article-title":"Partially parametric techniques for multiple imputation","volume":"22","author":"Schenker","year":"1996","journal-title":"Comput. Stat. Data Anal."},{"key":"ref81","doi-asserted-by":"publisher","first-page":"106","DOI":"10.1016\/j.bbr.2008.02.016","article-title":"Soluble oligomers of the amyloid beta-protein impair synaptic plasticity and behavior","volume":"192","author":"Selkoe","year":"2008","journal-title":"Behav. Brain Res."},{"key":"ref82","doi-asserted-by":"publisher","first-page":"379","DOI":"10.1002\/j.1538-7305.1948.tb01338.x","article-title":"A mathematical theory of communication","volume":"27","author":"Shannon","year":"1948","journal-title":"Bell Syst. Tech. J."},{"key":"ref83","doi-asserted-by":"publisher","first-page":"688","DOI":"10.1038\/163688a0","article-title":"Measurement of diversity","volume":"163","author":"Simpson","year":"1949","journal-title":"Nature"},{"key":"ref84","doi-asserted-by":"publisher","first-page":"1389638","DOI":"10.3389\/fnut.2024.1389638","article-title":"Gut microbes differ in postmenopausal women responding to prunes to maintain hip bone mineral density","volume":"11","author":"Simpson","year":"2024","journal-title":"Front. Nutr."},{"key":"ref85","doi-asserted-by":"publisher","first-page":"402","DOI":"10.1016\/j.jconrel.2024.01.047","article-title":"Alzheimer\u2019s disease current therapies, novel drug delivery systems and future directions for better disease management","volume":"367","author":"Singh","year":"2024","journal-title":"J. Control. Release"},{"key":"ref86","doi-asserted-by":"publisher","first-page":"7820","DOI":"10.3390\/ijms23147820","article-title":"The role of psychobiotics in supporting the treatment of disturbances in the functioning of the nervous system\u2014a systematic review","volume":"23","author":"Skowron","year":"2022","journal-title":"Int. J. Mol. Sci."},{"key":"ref87","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1177\/0023677217724823","article-title":"PREPARE: guidelines for planning animal research and testing","volume":"52","author":"Smith","year":"2018","journal-title":"Lab. Anim."},{"key":"ref88","doi-asserted-by":"publisher","first-page":"647","DOI":"10.1016\/j.physbeh.2003.11.003","article-title":"Amyloid-\u03b2(25\u201335)-induced memory impairments correlate with cell loss in rat hippocampus","volume":"80","author":"Stepanichev","year":"2004","journal-title":"Physiol. Behav."},{"key":"ref89","doi-asserted-by":"publisher","first-page":"367","DOI":"10.1007\/BF00428203","article-title":"The tail suspension test: a new method for screening antidepressants in mice","volume":"85","author":"Steru","year":"1985","journal-title":"Psychopharmacology"},{"key":"ref90","doi-asserted-by":"publisher","first-page":"fcac016","DOI":"10.1093\/braincomms\/fcac016","article-title":"Regional amyloid correlates of cognitive performance in ageing and mild cognitive impairment","volume":"4","author":"Stevens","year":"2022","journal-title":"Brain Commun."},{"key":"ref91","doi-asserted-by":"publisher","first-page":"11883","DOI":"10.1096\/fj.201903128RR","article-title":"Alzheimer\u2019s disease in the gut\u2014major changes in the gut of 5xFAD model mice with ApoA1 as potential key player","volume":"34","author":"Stoye","year":"2020","journal-title":"FASEB J."},{"key":"ref92","doi-asserted-by":"publisher","first-page":"222","DOI":"10.1111\/fcp.12512","article-title":"Effects of hippocampal histone acetylation and HDAC inhibition on spatial learning and memory in the Morris water maze in rats","volume":"34","author":"Topuz","year":"2020","journal-title":"Fundam. Clin. Pharmacol."},{"key":"ref93","doi-asserted-by":"publisher","first-page":"124","DOI":"10.5056\/jnm16042","article-title":"Colonic transit time is a driven force of the gut microbiota composition and metabolism: in vitro evidence","volume":"23","author":"Tottey","year":"2017","journal-title":"J. Neurogastroenterol. Motil."},{"key":"ref94","doi-asserted-by":"publisher","first-page":"1650","DOI":"10.1113\/EP087862","article-title":"Differences in neurocognitive performance and metabolic and inflammatory indices in male adults with obesity as a function of regular exercise","volume":"104","author":"Tsai","year":"2019","journal-title":"Exp. Physiol."},{"key":"ref95","doi-asserted-by":"crossref","DOI":"10.1201\/9780429492259","volume-title":"Flexible imputation of missing data, second edition","author":"van Buuren","year":"2018"},{"key":"ref96","doi-asserted-by":"publisher","first-page":"794519","DOI":"10.3389\/fimmu.2021.794519","article-title":"Gut microbiota composition is related to AD pathology","volume":"12","author":"Verhaar","year":"2022","journal-title":"Front. Immunol."},{"key":"ref97","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1016\/j.bbi.2024.08.022","article-title":"Prebiotics mitigate the detrimental effects of high-fat diet on memory, anxiety and microglia functionality in ageing mice","volume":"122","author":"Vijaya","year":"2024","journal-title":"Brain Behav. Immun."},{"key":"ref98","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1016\/j.nbd.2017.01.004","article-title":"Reversal of high fat diet-induced obesity improves glucose tolerance, inflammatory response, \u03b2-amyloid accumulation and cognitive decline in the APP\/PSEN1 mouse model of Alzheimer\u2019s disease","volume":"100","author":"Walker","year":"2017","journal-title":"Neurobiol. Dis."},{"key":"ref99","doi-asserted-by":"publisher","first-page":"355","DOI":"10.3233\/JAD-161226","article-title":"Diagnostic biomarkers of Alzheimer\u2019s disease as identified in saliva using 1H NMR-based metabolomics","volume":"58","author":"Yilmaz","year":"2017","journal-title":"J. Alzheimers Dis."},{"key":"ref100","doi-asserted-by":"publisher","first-page":"582218","DOI":"10.3389\/fnana.2020.582218","article-title":"Immunofluorescence staining of paraffin sections step by step","volume":"14","author":"Zaqout","year":"2020","journal-title":"Front. Neuroanat."},{"key":"ref101","doi-asserted-by":"publisher","first-page":"1241","DOI":"10.3233\/JAD-170020","article-title":"Altered gut microbiota in a mouse model of Alzheimer\u2019s disease","volume":"60","author":"Zhang","year":"2017","journal-title":"J. Alzheimers Dis."},{"key":"ref102","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1186\/s40035-023-00391-9","article-title":"Supplementation with high-GABA-producing Lactobacillus plantarum L5 ameliorates essential tremor triggered by decreased gut bacteria-derived GABA","volume":"12","author":"Zhong","year":"2023","journal-title":"Transl. Neurodegener."},{"key":"ref103","doi-asserted-by":"publisher","first-page":"310","DOI":"10.1111\/cns.12677","article-title":"The role of neuroinflammation and amyloid in cognitive impairment in an APP\/PS1 transgenic mouse model of Alzheimer\u2019s disease","volume":"23","author":"Zhu","year":"2017","journal-title":"CNS Neurosci. Ther."}],"container-title":["Frontiers in Aging Neuroscience"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnagi.2025.1617980\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,30]],"date-time":"2025-06-30T01:26:17Z","timestamp":1751246777000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnagi.2025.1617980\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,30]]},"references-count":104,"alternative-id":["10.3389\/fnagi.2025.1617980"],"URL":"https:\/\/doi.org\/10.3389\/fnagi.2025.1617980","relation":{},"ISSN":["1663-4365"],"issn-type":[{"value":"1663-4365","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,30]]},"article-number":"1617980"}}