{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T15:55:40Z","timestamp":1784649340356,"version":"3.55.0"},"reference-count":36,"publisher":"Public Library of Science (PLoS)","issue":"8","license":[{"start":{"date-parts":[[2022,8,24]],"date-time":"2022-08-24T00:00:00Z","timestamp":1661299200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>The key role played by host-microbiota interactions on human health, disease onset and progression, and on host response to treatments has increasingly emerged in the latest decades. Indeed, dysbiosis has been associated to several human diseases such as obesity, diabetes, cancer and also neurodegenerative disease, such as Parkinson, Huntington and Alzheimer\u2019s disease (AD), although whether causative, consequence or merely an epiphenomenon is still under investigation. In the present study, we performed a metabologenomic analysis of stool samples from a mouse model of AD, the 3xTgAD. We found a significant change in the microbiota of AD mice compared to WT, with a longitudinal divergence of the F\/B ratio, a parameter suggesting a gut dysbiosis. Moreover, AD mice showed a significant decrease of some amino acids, while data integration revealed a dysregulated production of desaminotyrosine (DAT) and dihydro-3-coumaric acid. Collectively, our data show a dysregulated gut microbiota associated to the onset and progression of AD, also indicating that a dysbiosis can occur prior to significant clinical signs, evidenced by early SCFA alterations, compatible with gut inflammation.<\/jats:p>","DOI":"10.1371\/journal.pone.0273036","type":"journal-article","created":{"date-parts":[[2022,8,24]],"date-time":"2022-08-24T17:41:24Z","timestamp":1661362884000},"page":"e0273036","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":15,"title":["A Metabologenomic approach reveals alterations in the gut microbiota of a mouse model of Alzheimer\u2019s disease"],"prefix":"10.1371","volume":"17","author":[{"given":"Francesco","family":"Favero","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elettra","family":"Barberis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mara","family":"Gagliardi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Espinoza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liliana","family":"Contu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Gustincich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Boccafoschi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Borsotti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dmitry","family":"Lim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vito","family":"Rubino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Flavio","family":"Mignone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edoardo","family":"Pasolli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcello","family":"Manfredi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Zucchelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Davide","family":"Cor\u00e0","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6246-5968","authenticated-orcid":true,"given":"Marco","family":"Corazzari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2022,8,24]]},"reference":[{"key":"pone.0273036.ref001","doi-asserted-by":"crossref","first-page":"1221","DOI":"10.1210\/me.2014-1108","article-title":"Minireview: Gut microbiota: the neglected endocrine organ","volume":"28","author":"G Clarke","year":"2014","journal-title":"Mol Endocrinol"},{"key":"pone.0273036.ref002","doi-asserted-by":"crossref","first-page":"1635","DOI":"10.1126\/science.1110591","article-title":"Diversity of the human intestinal microbial flora","volume":"308","author":"PB Eckburg","year":"2005","journal-title":"Science"},{"key":"pone.0273036.ref003","doi-asserted-by":"crossref","DOI":"10.3390\/nu11030521","article-title":"Autism Spectrum Disorders and the Gut Microbiota","volume":"11","author":"A Fattorusso","year":"2019","journal-title":"Nutrients"},{"key":"pone.0273036.ref004","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/j.tim.2018.09.008","article-title":"The Human Microbiome and Child Growth\u2014First 1000 Days and Beyond","volume":"27","author":"RC Robertson","year":"2019","journal-title":"Trends Microbiol"},{"key":"pone.0273036.ref005","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.gpb.2018.10.002","article-title":"Intestinal Microbiota in Early Life and Its Implications on Childhood Health","volume":"17","author":"L Zhuang","year":"2019","journal-title":"Genomics Proteomics Bioinformatics"},{"key":"pone.0273036.ref006","doi-asserted-by":"crossref","first-page":"267","DOI":"10.3233\/NHA-170030","article-title":"Gut microbiome and aging: Physiological and mechanistic insights","volume":"4","author":"R Nagpal","year":"2018","journal-title":"Nutr Healthy Aging"},{"key":"pone.0273036.ref007","article-title":"Microbiome evolution during host aging","volume":"15","author":"FDD Aleman","year":"2019","journal-title":"PLoS Pathog"},{"key":"pone.0273036.ref008","doi-asserted-by":"crossref","DOI":"10.1038\/s41598-019-49452-y","article-title":"Defining Dysbiosis for a Cluster of Chronic Diseases","volume":"9","author":"LJ Wilkins","year":"2019","journal-title":"Sci Rep"},{"key":"pone.0273036.ref009","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1002\/mds.26069","article-title":"Gut microbiota are related to Parkinson\u2019s disease and clinical phenotype","volume":"30","author":"F Scheperjans","year":"2015","journal-title":"Mov Disord"},{"key":"pone.0273036.ref010","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1016\/j.bbi.2019.05.008","article-title":"Altered microbiomes distinguish Alzheimer\u2019s disease from amnestic mild cognitive impairment and health in a Chinese cohort","volume":"80","author":"P Liu","year":"2019","journal-title":"Brain Behav Immun"},{"key":"pone.0273036.ref011","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1111\/lam.12882","article-title":"Shifts in gut microbiota composition in an APP\/PSS1 transgenic mouse model of Alzheimer\u2019s disease during lifespan","volume":"66","author":"C B\u00e4uerl","year":"2018","journal-title":"Lett Appl Microbiol"},{"key":"pone.0273036.ref012","doi-asserted-by":"crossref","first-page":"1768","DOI":"10.4103\/1673-5374.306072","article-title":"Probiotics, prebiotics and their role in Alzheimer\u2019s disease","volume":"16","author":"V D\u2019Argenio","year":"2021","journal-title":"Neural Regen Res"},{"key":"pone.0273036.ref013","doi-asserted-by":"crossref","DOI":"10.3390\/ijms19124079","article-title":"A Metabologenomic Approach Reveals Changes in the Intestinal Environment of Mice Fed on American Diet","volume":"19","author":"C Ishii","year":"2018","journal-title":"Int J Mol Sci"},{"key":"pone.0273036.ref014","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1016\/S0896-6273(03)00434-3","article-title":"Triple-transgenic model of Alzheimer\u2019s disease with plaques and tangles: intracellular Abeta and synaptic dysfunction","volume":"39","author":"S Oddo","year":"2003","journal-title":"Neuron"},{"key":"pone.0273036.ref015","doi-asserted-by":"crossref","DOI":"10.1016\/j.jprot.2019.103450","article-title":"Leonardo\u2019s Donna Nuda unveiled","volume":"207","author":"E Barberis","year":"2019","journal-title":"J Proteomics"},{"key":"pone.0273036.ref016","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1016\/j.jprot.2018.10.017","article-title":"Integrated serum proteins and fatty acids analysis for putative biomarker discovery in inflammatory bowel disease","volume":"195","author":"M Manfredi","year":"2019","journal-title":"J Proteomics"},{"key":"pone.0273036.ref017","doi-asserted-by":"crossref","DOI":"10.1016\/j.aca.2021.338841","article-title":"A new method for investigating microbiota-produced small molecules in adenomatous polyps","volume":"1179","author":"E Barberis","year":"2021","journal-title":"Anal Chim Acta"},{"key":"pone.0273036.ref018","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1038\/s41596-019-0264-1","article-title":"Using MicrobiomeAnalyst for comprehensive statistical, functional, and meta-analysis of microbiome data","volume":"15","author":"J Chong","year":"2020","journal-title":"Nat Protoc"},{"key":"pone.0273036.ref019","doi-asserted-by":"crossref","first-page":"1575","DOI":"10.1007\/s10072-013-1289-9","article-title":"Alzheimer\u2019s disease: amino acid levels and brain metabolic status","volume":"34","author":"MC Gueli","year":"2013","journal-title":"Neurol Sci"},{"key":"pone.0273036.ref020","article-title":"d-glutamate and Gut Microbiota in Alzheimer\u2019s Disease","volume":"21","author":"CH Chang","year":"2020","journal-title":"Int J Mol Sci"},{"key":"pone.0273036.ref021","first-page":"459","article-title":"Microbiome and Gut Dysbiosis","volume":"109","author":"JE Beliz\u00e1rio","year":"2018","journal-title":"Exp Suppl"},{"key":"pone.0273036.ref022","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1111\/cei.12474","article-title":"Immune homeostasis, dysbiosis and therapeutic modulation of the gut microbiota","volume":"179","author":"CT Peterson","year":"2015","journal-title":"Clin Exp Immunol"},{"key":"pone.0273036.ref023","doi-asserted-by":"crossref","first-page":"1659","DOI":"10.1038\/ajg.2016.227","article-title":"No Change in the Mucosal Gut Mycobioma Is Associated with Celiac Disease-Specific Microbiome Alteration in Adult Patients","volume":"111","author":"V D\u2019Argenio","year":"2016","journal-title":"Am J Gastroenterol"},{"key":"pone.0273036.ref024","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1016\/j.clinthera.2016.12.014","article-title":"Target Intestinal Microbiota to Alleviate Disease Progression in Amyotrophic Lateral Sclerosis","volume":"39","author":"Zhang Y guo","year":"2017","journal-title":"Clin Ther"},{"key":"pone.0273036.ref025","doi-asserted-by":"crossref","DOI":"10.3390\/ijerph15081679","article-title":"Rebuilding the Gut Microbiota Ecosystem","volume":"15","author":"A Gagliardi","year":"2018","journal-title":"Int J Environ Res Public Health"},{"key":"pone.0273036.ref026","doi-asserted-by":"crossref","DOI":"10.1128\/mBio.00632-19","article-title":"Alzheimer\u2019s Disease Microbiome Is Associated with Dysregulation of the Anti-Inflammatory P-Glycoprotein Pathway","volume":"10","author":"JP Haran","year":"2019","journal-title":"mBio"},{"key":"pone.0273036.ref027","doi-asserted-by":"crossref","DOI":"10.1038\/srep03957","article-title":"Insights into the distribution and abundance of the ubiquitous candidatus Saccharibacteria phylum following tag pyrosequencing","volume":"4","author":"B Ferrari","year":"2014","journal-title":"Sci Rep"},{"key":"pone.0273036.ref028","article-title":"Microbial imbalance in inflammatory bowel disease patients at different taxonomic levels","volume":"12","author":"MT Alam","year":"2020","journal-title":"Gut Pathog"},{"key":"pone.0273036.ref029","doi-asserted-by":"crossref","first-page":"1877","DOI":"10.1152\/physrev.00018.2018","article-title":"The Microbiota-Gut-Brain Axis","volume":"99","author":"O Cryan JF","year":"2019","journal-title":"Physiol Rev"},{"key":"pone.0273036.ref030","first-page":"2017","article-title":"Amino Acid Catabolism in Alzheimer\u2019s Disease Brain: Friend or Foe?","author":"JWD Griffin","year":"2017","journal-title":"Oxid Med Cell Longev"},{"key":"pone.0273036.ref031","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1126\/science.1241165","article-title":"The microbial metabolites, short-chain fatty acids, regulate colonic Treg cell homeostasis","volume":"341","author":"PM Smith","year":"2013","journal-title":"Science"},{"key":"pone.0273036.ref032","article-title":"Short Chain Fatty Acids (SCFAs)-Mediated Gut Epithelial and Immune Regulation and Its Relevance for Inflammatory Bowel Diseases","volume":"10","author":"DP Venegas","year":"2019","journal-title":"Front Immunol"},{"key":"pone.0273036.ref033","doi-asserted-by":"crossref","DOI":"10.3390\/microorganisms4020020","article-title":"Microbiome, Metabolome and Inflammatory Bowel Disease","volume":"4","author":"I Ahmed","year":"2016","journal-title":"Microorganisms"},{"key":"pone.0273036.ref034","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1038\/nri.2017.139","article-title":"Immunometabolism in 2017: Driving immunity: all roads lead to metabolism","volume":"18","author":"EJ Pearce","year":"2018","journal-title":"Nat Rev Immunol"},{"key":"pone.0273036.ref035","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1126\/science.aam5336","article-title":"The microbial metabolite desaminotyrosine protects from influenza through type I interferon","volume":"357","author":"AL Steed","year":"2017","journal-title":"Science"},{"key":"pone.0273036.ref036","doi-asserted-by":"crossref","first-page":"1025","DOI":"10.1002\/mnfr.201400544","article-title":"Role of intestinal microbiota in the generation of polyphenol-derived phenolic acid mediated attenuation of Alzheimer\u2019s disease \u03b2-amyloid oligomerization","volume":"59","author":"D Wang","year":"2015","journal-title":"Mol Nutr Food Res"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0273036","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,2,15]],"date-time":"2023-02-15T21:11:39Z","timestamp":1676495499000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0273036"}},"subtitle":[],"editor":[{"given":"Shahid","family":"Umar","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2022,8,24]]},"references-count":36,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2022,8,24]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0273036","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,8,24]]}}}