{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T15:00:20Z","timestamp":1787238020826,"version":"build-2736575974"},"reference-count":61,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T00:00:00Z","timestamp":1760054400000},"content-version":"vor","delay-in-days":9,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T00:00:00Z","timestamp":1759276800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Brain and Behavior"],"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Alzheimer's disease (AD) is a progressive neurodegenerative disorder that poses a major global health challenge due to its increasing prevalence and lack of effective treatments. Emerging evidence suggests the gut\u2013brain axis may play a pivotal role in AD pathogenesis. However, causal links between dysbiosis and late\u2010stage AD pathology remain unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      This study evaluated the effects of antibiotic\u2010induced gut dysbiosis in aged 3xTg\u2010AD mice (46\u201348\u00a0weeks). Female mice were randomly assigned to control or treatment groups and administered a broad\u2010spectrum antibiotic cocktail (ampicillin, vancomycin, and neomycin) for 14\u00a0days. Behavioral tests (Y\u2010maze, elevated plus maze) were performed to assess cognitive and anxiety\u2010like behaviors. Gut microbiota composition was assessed via 16S rRNA qPCR. Gene expression of Acetylcholinesterase (AChE), Butyrylcholinesterase (BChE), and Tumor Necrosis Factor\u2010Alpha (TNF\u2010\u03b1) was analyzed via qRT\u2010PCR, and cerebral amyloid\u2010\u03b2\n                      <jats:sub>1\u201342<\/jats:sub>\n                      and tau protein levels were quantified by ELISA.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Antibiotic treatment induced significant dysbiosis, with &gt;\u00a090% reduction in Firmicutes and Bacteroidetes. Dysbiotic mice displayed impaired spatial working memory, heightened anxiety\u2010like behavior, and reduced locomotor activity. Molecular analyses revealed region\u2010specific dysregulation of cholinergic genes: AChE was upregulated in the hippocampus but downregulated in the cortex, while BChE showed the opposite trend. TNF\u2010\u03b1 was significantly elevated in both regions, indicating neuroinflammation. Dysbiosis also led to increased brain levels of amyloid\u2010\u03b2\n                      <jats:sub>1\u201342<\/jats:sub>\n                      and tau.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Gut microbiome disruption exacerbates late\u2010stage AD pathology, driving cognitive deficits, neuroinflammation, and hallmark protein aggregation. These findings support the gut\u2013brain axis as a critical modulator of AD and highlight the microbiome as a potential therapeutic target.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/brb3.70946","type":"journal-article","created":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T08:30:09Z","timestamp":1760085009000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Antibiotic\u2010Induced Gut Dysbiosis Modulates Alzheimer's Disease\u2010Associated Gene Expression and Protein Aggregation in 3xTg\u2010AD Mice via the Gut\u2013Brain Axis"],"prefix":"10.1002","volume":"15","author":[{"given":"Edward Jenner","family":"Tettevi","sequence":"first","affiliation":[{"name":"Department of Biochemistry, Cell and Molecular Biology, School of Biological Science, Volta Road University of Ghana  Accra Ghana"},{"name":"West African Centre For Cell Biology of Infectious Pathogens, School of Biological Science, Volta Road University of Ghana  Accra Ghana"},{"name":"Council For Scientific and Industrial Research\u2010Water Research Institute, Biomedical and Public Health Research Unit, Agostinho Neto Road, Council Close, Airport Residential  Accra Ghana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David Larbi","family":"Simpong","sequence":"additional","affiliation":[{"name":"Department of Medical Laboratory Sciences, College of Health and Allied Sciences University of Cape Coast  Cape Coast Ghana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahmoud","family":"Maina","sequence":"additional","affiliation":[{"name":"Serpell Laboratory, Sussex Neuroscience, School of Life Sciences University of Sussex  Brighton UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel","family":"Adjei","sequence":"additional","affiliation":[{"name":"Department of Animal Experimentation, Noguchi Memorial Institute for Medical Research, College of Health Sciences University of Ghana  Accra Ghana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elias","family":"Asuming\u2010Brempong","sequence":"additional","affiliation":[{"name":"Council For Scientific and Industrial Research\u2010Water Research Institute, Biomedical and Public Health Research Unit, Agostinho Neto Road, Council Close, Airport Residential  Accra Ghana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mike Y.","family":"Osei\u2010Atweneboana","sequence":"additional","affiliation":[{"name":"CSIR\u2010College of Science and Technology, second CSIR Close, Behind Lancaster, Airport Residential  Accra Ghana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Augustine","family":"Ocloo","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Cell and Molecular Biology, School of Biological Science, Volta Road University of Ghana  Accra 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