{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T03:06:47Z","timestamp":1790996807963,"version":"4.1.0"},"reference-count":63,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,11,1]],"date-time":"2021-11-01T00:00:00Z","timestamp":1635724800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012659","name":"Foundation for Innovative Research Groups of the National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100012659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012659","name":"Foundation for Innovative Research Groups of the National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100012659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Aging Neurosci."],"abstract":"<jats:p>\n                    Vitamin A deficiency (VAD) plays an essential role in the pathogenesis of Alzheimer\u2019s disease (AD). However, the specific mechanism by which VAD aggravates cognitive impairment is still unknown. At the intersection of microbiology and neuroscience, the gut-brain axis is undoubtedly contributing to the formation and function of neurological systems, but most of the previous studies have ignored the influence of gut microbiota on the cognitive function in VAD. Therefore, we assessed the effect of VAD on AD pathology and the decline of cognitive function in AD model mice and determined the role played by the intestinal microbiota in the process. Twenty 8-week-old male C57BL\/6J amyloid precursor protein\/presenilin 1 (APP\/PS1) transgenic mice were randomly assigned to either a vitamin A normal (VAN) or VAD diet for 45 weeks. Our results show that VAD aggravated the behavioral learning and memory deficits, reduced the retinol concentration in the liver and the serum, decreased the transcription of vitamin A (VA)-related receptors and VA-related enzymes in the cortex, increased amyloid-\u03b2 peptides (A\u03b240 and A\u03b242) in the brain and gut, upregulate the translation of beta-site APP-cleaving enzyme 1 (BACE1) and phosphorylated Tau in the cortex, and downregulate the expression of brain-derived neurotrophic factor (BDNF) and \u03b3-aminobutyric acid (GABA) receptors in the cortex. In addition, VAD altered the composition and functionality of the fecal microbiota as exemplified by a decreased abundance of\n                    <jats:italic>Lactobacillus<\/jats:italic>\n                    and significantly different \u03b1- and \u03b2-diversity. Of note, the functional metagenomic prediction (PICRUSt analysis) indicated that GABAergic synapse and retinol metabolism decreased remarkably after VAD intervention, which was in line with the decreased expression of GABA receptors and the decreased liver and serum retinol. In summary, the present study provided valuable facts that VAD exacerbated the morphological, histopathological, molecular biological, microbiological, and behavioral impairment in the APP\/PS1 transgenic mice, and the intestinal microbiota may play a key mediator role in this mechanism.\n                  <\/jats:p>","DOI":"10.3389\/fnagi.2021.753351","type":"journal-article","created":{"date-parts":[[2021,11,1]],"date-time":"2021-11-01T03:33:17Z","timestamp":1635737597000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":41,"title":["Vitamin A Deficiency Exacerbates Gut Microbiota Dysbiosis and Cognitive Deficits in Amyloid Precursor Protein\/Presenilin 1 Transgenic Mice"],"prefix":"10.3389","volume":"13","author":[{"given":"Bo-Wen","family":"Chen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai-Wen","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Si-Jia","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chun","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng-Gao","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,11,1]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1016\/j.jnutbio.2008.01.002","article-title":"Bacterial population and innate immunity-related genes in rat gastrointestinal tract are altered by vitamin A-deficient diet.","volume":"20","author":"Amit-Romach","year":"2009","journal-title":"J. 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