{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T14:27:03Z","timestamp":1774362423049,"version":"3.50.1"},"reference-count":45,"publisher":"Springer Science and Business Media LLC","issue":"S3","content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Syst Biol"],"published-print":{"date-parts":[[2016,8]]},"DOI":"10.1186\/s12918-016-0307-y","type":"journal-article","created":{"date-parts":[[2016,8,26]],"date-time":"2016-08-26T08:41:56Z","timestamp":1472200916000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":145,"title":["Towards understanding brain-gut-microbiome connections in Alzheimer\u2019s disease"],"prefix":"10.1186","volume":"10","author":[{"given":"Rong","family":"Xu","sequence":"first","affiliation":[]},{"given":"QuanQiu","family":"Wang","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2016,8,26]]},"reference":[{"issue":"6086","key":"307_CR1","doi-asserted-by":"crossref","first-page":"1262","DOI":"10.1126\/science.1223813","volume":"336","author":"JK Nicholson","year":"2012","unstructured":"Nicholson JK, Holmes E, Kinross J, Burcelin R, Gibson G, Jia W, Pettersson S. Host-gut microbiota metabolic interactions. Science. 2012; 336(6086):1262\u20137.","journal-title":"Science"},{"issue":"7415","key":"307_CR2","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1038\/nature11552","volume":"489","author":"V Tremaroli","year":"2012","unstructured":"Tremaroli V, Backhed F. Functional interactions between the gut microbiota and host metabolism. Nature. 2012; 489(7415):242\u20139.","journal-title":"Nature"},{"issue":"10","key":"307_CR3","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1038\/nrn3346","volume":"13","author":"JF Cryan","year":"2012","unstructured":"Cryan JF, Dinan TG. Mind-altering microorganisms: the impact of the gut microbiota on brain and behaviour. Nat Rev Neurosci. 2012; 13(10):701\u201312.","journal-title":"Nat Rev Neurosci"},{"issue":"5778","key":"307_CR4","doi-asserted-by":"crossref","first-page":"1355","DOI":"10.1126\/science.1124234","volume":"312","author":"SR Gill","year":"2006","unstructured":"Gill SR, Pop M, DeBoy RT, Eckburg PB, Turnbaugh PJ, Samuel BS, Nelson KE. Metagenomic analysis of the human distal gut microbiome. Science. 2006; 312(5778):1355\u20139.","journal-title":"Science"},{"issue":"7","key":"307_CR5","doi-asserted-by":"crossref","first-page":"1451","DOI":"10.1016\/j.cell.2013.11.024","volume":"155","author":"EY Hsiao","year":"2013","unstructured":"Hsiao EY, McBride SW, Hsien S, Sharon G, Hyde ER, McCue T, Mazmanian SK. Microbiota modulate behavioral and physiological abnormalities associated with neurodevelopmental disorders. Cell. 2013; 155(7):1451\u201363.","journal-title":"Cell"},{"issue":"96","key":"307_CR6","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1126\/scitranslmed.3002648","volume":"3","author":"JT Dudley","year":"2011","unstructured":"Dudley JT, Sirota M, Shenoy M, Pai RK, Roedder S, Chiang AP, Butte AJ. Computational repositioning of the anticonvulsant topiramate for inflammatory bowel disease. Sci Transl Med. 2011; 3(96):96\u2013769676.","journal-title":"Sci Transl Med"},{"issue":"96","key":"307_CR7","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1126\/scitranslmed.3001318","volume":"3","author":"M Sirota","year":"2011","unstructured":"Sirota M, Dudley JT, Kim J, Chiang AP, Morgan AA, Sweet-Cordero A, Butte AJ. Discovery and preclinical validation of drug indications using compendia of public gene expression data. Sci Transl Med. 2011; 3(96):96\u2013779677.","journal-title":"Sci Transl Med"},{"key":"307_CR8","unstructured":"Wang Q, Xu R. DenguePredict: an integrated drug repositioning system towards drug discovery for dengue. AMIA Annu Symp Proc. 2015: 2015. p. 1279\u201388."},{"key":"307_CR9","doi-asserted-by":"crossref","unstructured":"Xu R, Wang Q. Phenopredict: a disease phenome-wide drug repositioning approach towards schizophrenia drug discovery. J Biomed Inform. 2015:348\u201355. [doi: 10.1016\/j.jbi.2015.06.027 ].","DOI":"10.1016\/j.jbi.2015.06.027"},{"key":"307_CR10","unstructured":"Chen Y, Cai X, Xu R. Combing Human Disease Genetics and Mouse Model Phenotypes Towards Drug Repositioning for Parkinson\u2019s Disease. AMIA Annu Symp Proc. 2015: 2015. p. 1851\u201360."},{"issue":"8","key":"307_CR11","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1038\/nrg3253","volume":"13","author":"Y Moreau","year":"2012","unstructured":"Moreau Y, Tranchevent LC. Computational tools for prioritizing candidate genes: boosting disease gene discovery. Nat Rev Genet. 2012; 13(8):523\u201336.","journal-title":"Nat Rev Genet"},{"issue":"12","key":"307_CR12","doi-asserted-by":"crossref","first-page":"i276","DOI":"10.1093\/bioinformatics\/btv245","volume":"31","author":"Y Chen","year":"2015","unstructured":"Chen Y, Xu R. Phenome-driven disease genetics prediction towards drug discovery. Bioinformatics. 2015; 31(12):i276\u201383.","journal-title":"Bioinformatics"},{"issue":"Suppl 7","key":"307_CR13","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1186\/1471-2164-16-S7-S9","volume":"16","author":"Y Chen","year":"2015","unstructured":"Chen Y, Xu R. Network-based gene prediction for plasmodium falciparum malaria towards genetics-based drug discovery. BMC Genomics. 2015; 16(Suppl 7):9.","journal-title":"BMC Genomics"},{"issue":"Suppl 7","key":"307_CR14","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1186\/1471-2164-16-S7-S4","volume":"16","author":"R Xu","year":"2015","unstructured":"Xu R, Wang Q, Li L. Genome-wide systems analysis reveals strong link between colorectal cancer and trimethylamine n-oxide (tmao), a gut microbial metabolite of dietary meat and fat. BMC Genomics. 2015; 16(Suppl 7):4.","journal-title":"BMC Genomics"},{"issue":"Database issue","key":"307_CR15","doi-asserted-by":"crossref","first-page":"D801","DOI":"10.1093\/nar\/gks1065","volume":"41","author":"DS Wishart","year":"2013","unstructured":"Wishart DS, Jewison T, Guo AC, Wilson M, Knox C, Liu Y, Scalbert A. Hmdb 3.0\u2014the human metabolome database in 2013. Nucleic Acids Res. 2013; 41(Database issue):D801\u20137.","journal-title":"Nucleic Acids Res."},{"issue":"Database issue","key":"307_CR16","doi-asserted-by":"crossref","first-page":"D401","DOI":"10.1093\/nar\/gkt1207","volume":"42","author":"M Kuhn","year":"2014","unstructured":"Kuhn M, Szklarczyk D, Pletscher-Frankild S, Blicher TH, von Mering C, Jensen LJ, Bork P. Stitch 4: integration of protein\u2013chemical interactions with user data. Nucleic Acids Res. 2014; 42(Database issue):D401\u20137.","journal-title":"Nucleic Acids Res."},{"issue":"D1","key":"307_CR17","doi-asserted-by":"crossref","first-page":"1001","DOI":"10.1093\/nar\/gkt1229","volume":"42","author":"D Welter","year":"2014","unstructured":"Welter D, MacArthur J, Morales J, Burdett T, Hall P, Junkins H, Parkinson H. The nhgri gwas catalog, a curated resource of snp-trait associations. Nucleic Acids Res. 2014; 42(D1):1001\u20136.","journal-title":"Nucleic Acids Res"},{"issue":"suppl 1","key":"307_CR18","first-page":"514","volume":"33","author":"A Hamosh","year":"2005","unstructured":"Hamosh A, Scott AF, Amberger JS, Bocchini CA, McKusick VA. Online mendelian inheritance in man (omim), a knowledgebase of human genes and genetic disorders. Nucleic Acids Res. 2005; 33(suppl 1):514\u20137.","journal-title":"Nucleic Acids Res"},{"key":"307_CR19","doi-asserted-by":"crossref","first-page":"808","DOI":"10.1093\/nar\/gks1094","volume":"41(D1)","author":"A Franceschini","year":"2013","unstructured":"Franceschini A, Szklarczyk D, Frankild S, Kuhn M, Simonovic M. String v9. 1: protein-protein interaction networks, with increased coverage and integration. Nucleic Acids Res. 2013; 41(D1):808\u201315.","journal-title":"Nucleic Acids Res"},{"issue":"12","key":"307_CR20","doi-asserted-by":"crossref","first-page":"1739","DOI":"10.1093\/bioinformatics\/btr260","volume":"27","author":"A Liberzon","year":"2011","unstructured":"Liberzon A, Subramanian A, Pinchback R, Thorvaldsdottir H, Tamayo P, Mesirov JP. Molecular signatures database (msigdb) 3.0. Bioinformatics. 2011; 27(12):1739\u201340.","journal-title":"Bioinformatics"},{"key":"307_CR21","unstructured":"Han J, Kamber M, Pei J. Data Mining: Concepts and Techniques: Concepts and Techniques: Elsevier; 2011."},{"issue":"2","key":"307_CR22","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1093\/clinchem\/42.2.298","volume":"42","author":"HU Shetty","year":"1996","unstructured":"Shetty HU, Holloway HW, Schapiro MB. Cerebrospinal fluid and plasma distribution of myo-inositol and other polyols in alzheimer disease. Clin Chem. 1996; 42(2):298\u2013302.","journal-title":"Clin Chem"},{"issue":"5","key":"307_CR23","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1159\/000022031","volume":"44","author":"N Redjems-Bennani","year":"1998","unstructured":"Redjems-Bennani N, Jeandel C, Lefebvre E, Blain H, Vidailhet M, Gueant JL. Abnormal substrate levels that depend upon mitochondrial function in cerebrospinal fluid from alzheimer patients. Gerontology. 1998; 44(5):300\u20134.","journal-title":"Gerontology"},{"issue":"6","key":"307_CR24","doi-asserted-by":"crossref","first-page":"756","DOI":"10.1016\/S0006-3223(99)00008-6","volume":"46","author":"MA Raskind","year":"1999","unstructured":"Raskind MA, Peskind ER, Holmes C, Goldstein DS. Patterns of cerebrospinal fluid catechols support increased central noradrenergic responsiveness in aging and alzheimer\u2019s disease. Biol Psychiatry. 1999; 46(6):756\u201365.","journal-title":"Biol Psychiatry"},{"issue":"13","key":"307_CR25","doi-asserted-by":"crossref","first-page":"8591","DOI":"10.1074\/jbc.M510926200","volume":"281","author":"H Jiang","year":"2006","unstructured":"Jiang H, Jiang Q, Liu W, Feng J. Parkin suppresses the expression of monoamine oxidases. J Biol Chem. 2006; 281(13):8591\u20139.","journal-title":"J Biol Chem"},{"issue":"18","key":"307_CR26","doi-asserted-by":"crossref","first-page":"7619","DOI":"10.1073\/pnas.0902640106","volume":"106","author":"SE Kolstoe","year":"2009","unstructured":"Kolstoe SE, Ridha BH, Bellotti V, Wang N, Robinson CV, Crutch SJ, Pepys MB. Molecular dissection of alzheimer\u2019s disease neuropathology by depletion of serum amyloid p component. Proc Natl Acad Sci. 2009; 106(18):7619\u201323.","journal-title":"Proc Natl Acad Sci"},{"issue":"2","key":"307_CR27","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.molmed.2007.12.001","volume":"14","author":"RM Ramalho","year":"2008","unstructured":"Ramalho RM, Viana RJ, Low WC, Steer CJ, Rodrigues CM. Bile acids and apoptosis modulation: an emerging role in experimental alzheimer\u2019s disease. Trends Mol Med. 2008; 14(2):54\u201362.","journal-title":"Trends Mol Med"},{"issue":"1","key":"307_CR28","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.aca.2006.01.070","volume":"576","author":"MJ Paik","year":"2006","unstructured":"Paik MJ, Lee S, Cho KH, Kim KR. Urinary polyamines and n-acetylated polyamines in four patients with alzheimer\u2019s disease as their n-ethoxycarbonyl-n-pentafluoropropionyl derivatives by gas chromatography\u2013mass spectrometry in selected ion monitoring mode. Analytica Chimica Acta. 2006; 576(1):55\u201360.","journal-title":"Analytica Chimica Acta"},{"issue":"1","key":"307_CR29","doi-asserted-by":"crossref","first-page":"1107","DOI":"10.2741\/2130","volume":"12","author":"C Mancuso","year":"2007","unstructured":"Mancuso C, Scapagini G, Curro D, Giuffrida Stella AM, De Marco C, Butterfield DA, Calabrese V. Mitochondrial dysfunction, free radical generation and cellular stress response in neurodegenerative disorders. Front Biosci. 2007; 12(1):1107\u201323.","journal-title":"Front Biosci"},{"issue":"4","key":"307_CR30","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1016\/0891-5849(92)90184-I","volume":"13","author":"E Graf","year":"1992","unstructured":"Graf E. Antioxidant potential of ferulic acid. Free Radic Biol Med. 1992; 13(4):435\u201348.","journal-title":"Free Radic Biol Med"},{"issue":"2","key":"307_CR31","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1006\/bbrc.1998.9681","volume":"253","author":"LC Bourne","year":"1998","unstructured":"Bourne LC, Rice-Evans C. Bioavailability of ferulic acid. Biochem Biophys Res Commun. 1998; 253(2):222\u20137.","journal-title":"Biochem Biophys Res Commun"},{"issue":"14","key":"307_CR32","doi-asserted-by":"crossref","first-page":"3712","DOI":"10.1523\/JNEUROSCI.0059-07.2007","volume":"27","author":"TM Malm","year":"2007","unstructured":"Malm TM, Iivonen H, Goldsteins G, Keksa-Goldsteine V, Ahtoniemi T, Kanninen K, Koistinaho J. Pyrrolidine dithiocarbamate activates akt and improves spatial learning in app\/ps1 mice without affecting beta-amyloid burden. J Neurosci. 2007; 27(14):3712\u201321.","journal-title":"J Neurosci"},{"issue":"4","key":"307_CR33","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1006\/nbdi.2000.0304","volume":"7","author":"LM Refolo","year":"2000","unstructured":"Refolo LM, Pappolla MA, Malester B, LaFrancois J, Bryant-Thomas T, Wang R, Duff K. Hypercholesterolemia accelerates the alzheimer\u2019s amyloid pathology in a transgenic mouse model. Neurobiol Dis. 2000; 7(4):321\u201331.","journal-title":"Neurobiol Dis"},{"issue":"2","key":"307_CR34","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1016\/S0891-5849(02)00841-9","volume":"33","author":"MA Pappolla","year":"2002","unstructured":"Pappolla MA, Smith MA, Bryant-Thomas T, Bazan N, Petanceska S, Perry G, Refolo LM. Cholesterol, oxidative stress, and alzheimer\u2019s disease: expanding the horizons of pathogenesis. Free Radic Biol Med. 2002; 33(2):173\u201381.","journal-title":"Free Radic Biol Med"},{"issue":"2","key":"307_CR35","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1111\/j.1476-5381.2012.02057.x","volume":"167","author":"W Danysz","year":"2012","unstructured":"Danysz W, Parsons CG. Alzheimer\u2019s disease, beta-amyloid, glutamate, nmda receptors and memantine searching for the connections. Br J Pharmacol. 2012; 167(2):324\u201352.","journal-title":"Br J Pharmacol"},{"issue":"7341","key":"307_CR36","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1038\/nature09922","volume":"472","author":"Z Wang","year":"2011","unstructured":"Wang Z, Klipfell E, Bennett BJ, Koeth R, Levison BS, DuGar B, Hazen SL. Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease. Nature. 2011; 472(7341):57\u201363.","journal-title":"Nature"},{"issue":"1","key":"307_CR37","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.cmet.2012.12.011","volume":"17","author":"BJ Bennett","year":"2013","unstructured":"Bennett BJ, de Aguiar Vallim TQ, Z W, Shih DM, Meng Y, Gregory J, Lusis AJ. Trimethylamine-n-oxide, a metabolite associated with atherosclerosis, exhibits complex genetic and dietary regulation. Cell Metabolism. 2013; 17(1):49\u201360.","journal-title":"Cell Metabolism"},{"issue":"5","key":"307_CR38","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1038\/nm.3145","volume":"19","author":"RA Koeth","year":"2013","unstructured":"Koeth RA, Wang Z, Levison BS, Buffa JA, Sheehy BT, Britt EB, Hazen SL. Intestinal microbiota metabolism of l-carnitine, a nutrient in red meat, promotes atherosclerosis. Nat Med. 2013; 19(5):576\u201385.","journal-title":"Nat Med"},{"issue":"17","key":"307_CR39","doi-asserted-by":"crossref","first-page":"1575","DOI":"10.1056\/NEJMoa1109400","volume":"368","author":"WW Tang","year":"2013","unstructured":"Tang WW, Wang Z, Levison BS, Koeth RA, Britt EB, Fu X, Hazen S. L. Intestinal microbial metabolism of phosphatidylcholine and cardiovascular risk. N Engl J Med. 2013; 368(17):1575\u201384.","journal-title":"N Engl J Med"},{"issue":"2","key":"307_CR40","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1212\/01.WNL.0000103860.75218.A5","volume":"62","author":"S Kalmijn","year":"2004","unstructured":"Kalmijn S, Van Boxtel MPJ, Ocke M, Verschuren WMM, Kromhout D, Launer LJ. Dietary intake of fatty acids and fish in relation to cognitive performance at middle age. Neurology. 2004; 62(2):275\u201380.","journal-title":"Neurology"},{"issue":"4","key":"307_CR41","first-page":"1","volume":"27","author":"ML Daviglus","year":"2010","unstructured":"Daviglus ML, Bell CC, Berrettini W, Bowen PE, Connolly Jr ES, Cox NJ, Trevisan M. Nih state-of-the-science conference statement: preventing alzheimer\u2019s disease and cognitive decline. NIH Consensus State-of-the-science Statements. 2010; 27(4):1\u201330.","journal-title":"NIH Consensus State-of-the-science Statements"},{"issue":"9","key":"307_CR42","doi-asserted-by":"crossref","first-page":"1573","DOI":"10.1212\/01.WNL.0000123250.82849.B6","volume":"62","author":"MC Morris","year":"2004","unstructured":"Morris MC, Evans DA, Bienias JL, Tangney CC, Wilson RS. Dietary fat intake and 6-year cognitive change in an older biracial community population. Neurology. 2004; 62(9):1573\u20139.","journal-title":"Neurology"},{"issue":"1","key":"307_CR43","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1002\/ana.23593","volume":"72","author":"OI Okereke","year":"2012","unstructured":"Okereke OI, Rosner BA, Kim DH, Kang JH, Cook NR, Manson JE, Grodstein F. Dietary fat types and 4-year cognitive change in community-dwelling older women. Ann Neurol. 2012; 72(1):124\u201334.","journal-title":"Ann Neurol"},{"issue":"14","key":"307_CR44","doi-asserted-by":"crossref","first-page":"1279","DOI":"10.1056\/NEJMoa1200303","volume":"368","author":"R Estruch","year":"2013","unstructured":"Estruch R, Ros E, Salas-Salvado J, Covas MI, Corella D, Aros F, Martinez-Gonzalez MA. Primary prevention of cardiovascular disease with a mediterranean diet. N Engl J Med. 2013; 368(14):1279\u201390.","journal-title":"N Engl J Med"},{"issue":"3","key":"307_CR45","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1016\/j.amjmed.2014.10.014","volume":"128","author":"RJ Widmer","year":"2015","unstructured":"Widmer RJ, Flammer AJ, Lerman LO, Lerman A. The mediterranean diet, its components, and cardiovascular disease. Am J Med. 2015; 128(3):229\u201338.","journal-title":"Am J Med"}],"container-title":["BMC Systems Biology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s12918-016-0307-y","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,7,7]],"date-time":"2022-07-07T03:03:45Z","timestamp":1657163025000},"score":1,"resource":{"primary":{"URL":"http:\/\/bmcsystbiol.biomedcentral.com\/articles\/10.1186\/s12918-016-0307-y"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,8]]},"references-count":45,"journal-issue":{"issue":"S3","published-print":{"date-parts":[[2016,8]]}},"alternative-id":["307"],"URL":"https:\/\/doi.org\/10.1186\/s12918-016-0307-y","relation":{},"ISSN":["1752-0509"],"issn-type":[{"value":"1752-0509","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,8]]},"article-number":"63"}}