{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T03:29:05Z","timestamp":1793158145021,"version":"4.5.0"},"reference-count":31,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,8,15]],"date-time":"2025-08-15T00:00:00Z","timestamp":1755216000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2025,8,15]],"date-time":"2025-08-15T00:00:00Z","timestamp":1755216000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"DOI":"10.1038\/s41598-025-15355-4","type":"journal-article","created":{"date-parts":[[2025,8,15]],"date-time":"2025-08-15T05:58:51Z","timestamp":1755237531000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Strain specific effects of probiotic supplementation on serum amino acid profiles in Alzheimer\u2019s disease: a randomized, double blind, placebo controlled trial"],"prefix":"10.1038","volume":"15","author":[{"given":"Nagham","family":"Jouni","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camellia","family":"Akhgarjand","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zahra","family":"Vahabi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sakineh","family":"Shab-Bidar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hala","family":"Khalifeh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kurosh","family":"Djafarian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,8,15]]},"reference":[{"key":"15355_CR1","doi-asserted-by":"publisher","unstructured":"2023 Alzheimer\u2019s disease facts and figures. Alzheimer\u2019s Dementia 19, 1598\u20131695. https:\/\/doi.org\/10.1002\/alz.13016 (2023).","DOI":"10.1002\/alz.13016"},{"key":"15355_CR2","unstructured":"Organization, W. H. A Blueprint for Dementia Research (World Health Organization, 2022)."},{"key":"15355_CR3","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.jalz.2016.07.150","volume":"13","author":"A Wimo","year":"2017","unstructured":"Wimo, A. et al. The worldwide costs of dementia 2015 and comparisons with 2010. Alzheimer\u2019s Dement. 13, 1\u20137 (2017).","journal-title":"Alzheimer\u2019s Dement."},{"key":"15355_CR4","doi-asserted-by":"publisher","first-page":"e105","DOI":"10.1016\/S2468-2667(21)00249-8","volume":"7","author":"E Nichols","year":"2022","unstructured":"Nichols, E. et al. Estimation of the global prevalence of dementia in 2019 and forecasted prevalence in 2050: an analysis for the global burden of disease study 2019. Lancet Public. Health. 7, e105\u2013e125 (2022).","journal-title":"Lancet Public. Health"},{"key":"15355_CR5","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1159\/000466688","volume":"7","author":"G Corso","year":"2017","unstructured":"Corso, G. et al. Serum amino acid profiles in normal subjects and in patients with or at risk of alzheimer dementia. Dement. Geriatric Cogn. Disorders Extra. 7, 143\u2013159 (2017).","journal-title":"Dement. Geriatric Cogn. Disorders Extra"},{"key":"15355_CR6","doi-asserted-by":"publisher","first-page":"1460","DOI":"10.4103\/1673-5374.274328","volume":"15","author":"B Polis","year":"2020","unstructured":"Polis, B. & Samson, A. O. Role of the metabolism of branched-chain amino acids in the development of alzheimer\u2019s disease and other metabolic disorders. Neural Regeneration Res. 15, 1460\u20131470. https:\/\/doi.org\/10.4103\/1673-5374.274328 (2020).","journal-title":"Neural Regeneration Res."},{"key":"15355_CR7","doi-asserted-by":"publisher","first-page":"993","DOI":"10.1007\/s00726-021-03002-x","volume":"53","author":"G Ga\u0142\u0119zowska","year":"2021","unstructured":"Ga\u0142\u0119zowska, G., Ratajczyk, J. & Wolska, L. Determination of amino acids in human biological fluids by high-performance liquid chromatography: critical review. Amino Acids. 53, 993\u20131009 (2021).","journal-title":"Amino Acids"},{"key":"15355_CR8","doi-asserted-by":"publisher","first-page":"3523","DOI":"10.3390\/cells11213523","volume":"11","author":"MAB Siddik","year":"2022","unstructured":"Siddik, M. A. B. et al. Branched-chain amino acids are linked with alzheimer\u2019s disease-related pathology and cognitive deficits. Cells 11, 3523 (2022).","journal-title":"Cells"},{"key":"15355_CR9","doi-asserted-by":"publisher","first-page":"1403","DOI":"10.3390\/nu12051403","volume":"12","author":"T Fukuwatari","year":"2020","unstructured":"Fukuwatari, T. Possibility of amino acid treatment to prevent the psychiatric disorders via modulation of the production of Tryptophan metabolite kynurenic acid. Nutrients 12, 1403 (2020).","journal-title":"Nutrients"},{"key":"15355_CR10","doi-asserted-by":"publisher","first-page":"2836","DOI":"10.1111\/febs.15571","volume":"288","author":"L Bonfili","year":"2021","unstructured":"Bonfili, L. et al. Microbiota modulation as preventative and therapeutic approach in alzheimer\u2019s disease. FEBS J. 288, 2836\u20132855 (2021).","journal-title":"FEBS J."},{"key":"15355_CR11","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1016\/j.gtc.2016.09.007","volume":"46","author":"TG Dinan","year":"2017","unstructured":"Dinan, T. G. & Cryan, J. F. The microbiome-gut-brain axis in health and disease. Gastroenterol. Clin. 46, 77\u201389 (2017).","journal-title":"Gastroenterol. Clin."},{"key":"15355_CR12","doi-asserted-by":"publisher","first-page":"1106","DOI":"10.2174\/1389200219666180813144834","volume":"15","author":"F Leblhuber","year":"2018","unstructured":"Leblhuber, F., Steiner, K., Schuetz, B., Fuchs, D. & Gostner, J. M. Probiotic supplementation in patients with alzheimer\u2019s dementia-an explorative intervention study. Curr. Alzheimer Res. 15, 1106\u20131113 (2018).","journal-title":"Curr. Alzheimer Res."},{"key":"15355_CR13","doi-asserted-by":"publisher","first-page":"20","DOI":"10.3390\/nu14010020","volume":"14","author":"R Naomi","year":"2021","unstructured":"Naomi, R. et al. Probiotics for alzheimer\u2019s disease: a systematic review. Nutrients 14, 20 (2021).","journal-title":"Nutrients"},{"key":"15355_CR14","doi-asserted-by":"publisher","first-page":"2930","DOI":"10.3390\/nu7042930","volume":"7","author":"EP Neis","year":"2015","unstructured":"Neis, E. P., Dejong, C. H. & Rensen, S. S. The role of microbial amino acid metabolism in host metabolism. Nutrients 7, 2930\u20132946. https:\/\/doi.org\/10.3390\/nu7042930 (2015).","journal-title":"Nutrients"},{"key":"15355_CR15","doi-asserted-by":"publisher","first-page":"1083","DOI":"10.3233\/jad-200436","volume":"76","author":"H Kaur","year":"2020","unstructured":"Kaur, H. et al. Effects of probiotic supplementation on short chain fatty acids in the AppNL-G-F mouse model of alzheimer\u2019s disease. J. Alzheimer\u2019s Disease: JAD. 76, 1083\u20131102. https:\/\/doi.org\/10.3233\/jad-200436 (2020).","journal-title":"J. Alzheimer\u2019s Disease: JAD"},{"key":"15355_CR16","doi-asserted-by":"publisher","first-page":"755","DOI":"10.1017\/S0007114510004319","volume":"105","author":"M Messaoudi","year":"2011","unstructured":"Messaoudi, M. et al. Assessment of psychotropic-like properties of a probiotic formulation (Lactobacillus helveticus R0052 and bifidobacterium longum R0175) in rats and human subjects. Br. J. Nutr. 105, 755\u2013764 (2011).","journal-title":"Br. J. Nutr."},{"key":"15355_CR17","doi-asserted-by":"publisher","first-page":"1737","DOI":"10.3390\/nu15071737","volume":"15","author":"C Chu","year":"2023","unstructured":"Chu, C. et al. Lactobacillus plantarum CCFM405 against rotenone-induced parkinson\u2019s disease mice via regulating gut microbiota and branched-chain amino acids biosynthesis. Nutrients 15, 1737 (2023).","journal-title":"Nutrients"},{"key":"15355_CR18","doi-asserted-by":"crossref","unstructured":"Ghosh, D. In Nutraceuticals in Brain Health and Beyond3\u201313 (Elsevier, 2021).","DOI":"10.1016\/B978-0-12-820593-8.00002-1"},{"key":"15355_CR19","doi-asserted-by":"publisher","first-page":"420","DOI":"10.1136\/jnnp-2022-330619","volume":"94","author":"D Altomare","year":"2023","unstructured":"Altomare, D. et al. Plasma biomarkers for alzheimer\u2019s disease: a field-test in a memory clinic. J. Neurol. Neurosurg. Psychiatry. 94, 420\u2013427 (2023).","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"15355_CR20","doi-asserted-by":"publisher","first-page":"178","DOI":"10.1016\/j.tifs.2023.06.013","volume":"138","author":"T Ma","year":"2023","unstructured":"Ma, T. et al. Targeting gut microbiota and metabolism as the major probiotic mechanism - An evidence-based review. Trends Food Sci. Technol. 138, 178\u2013198. https:\/\/doi.org\/10.1016\/j.tifs.2023.06.013 (2023).","journal-title":"Trends Food Sci. Technol."},{"key":"15355_CR21","doi-asserted-by":"publisher","first-page":"650","DOI":"10.2471\/BLT.08.050955","volume":"86","author":"JR Williams","year":"2008","unstructured":"Williams, J. R. The declaration of Helsinki and public health. Bull. World Health Organ. 86, 650\u2013652 (2008).","journal-title":"Bull. World Health Organ."},{"key":"15355_CR22","doi-asserted-by":"publisher","first-page":"172","DOI":"10.1016\/j.jalz.2018.05.006","volume":"15","author":"J Cummings","year":"2019","unstructured":"Cummings, J. The National Institute on Aging\u2014Alzheimer\u2019s association framework on alzheimer\u2019s disease: application to clinical trials. Alzheimer\u2019s Dement. 15, 172\u2013178 (2019).","journal-title":"Alzheimer\u2019s Dement."},{"key":"15355_CR23","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1017\/S1041610292001157","volume":"4","author":"SG Sclan","year":"1992","unstructured":"Sclan, S. G. & Reisberg, B. Functional assessment staging (FAST) in alzheimer\u2019s disease: reliability, validity, and ordinality. Int. Psychogeriatr. 4, 55\u201369 (1992).","journal-title":"Int. Psychogeriatr."},{"key":"15355_CR24","doi-asserted-by":"publisher","first-page":"1032494","DOI":"10.3389\/fnagi.2022.1032494","volume":"14","author":"C Akhgarjand","year":"2022","unstructured":"Akhgarjand, C., Vahabi, Z., Shab-Bidar, S., Etesam, F. & Djafarian, K. Effects of probiotic supplements on cognition, anxiety, and physical activity in subjects with mild and moderate alzheimer\u2019s disease: A randomized, double-blind, and placebo-controlled study. Front. Aging Neurosci. 14, 1032494 (2022).","journal-title":"Front. Aging Neurosci."},{"key":"15355_CR25","doi-asserted-by":"publisher","first-page":"2264","DOI":"10.1038\/s41598-020-59081-5","volume":"10","author":"L Latmiral","year":"2020","unstructured":"Latmiral, L. & Armata, F. Berry-Hannay relation in nonlinear optomechanics. Sci. Rep. 10, 2264 (2020).","journal-title":"Sci. Rep."},{"key":"15355_CR26","doi-asserted-by":"publisher","first-page":"101198","DOI":"10.1016\/j.arr.2020.101198","volume":"64","author":"DG Le Couteur","year":"2020","unstructured":"Le Couteur, D. G. et al. Branched chain amino acids, aging and age-related health. Ageing Res. Rev. 64, 101198 (2020).","journal-title":"Ageing Res. Rev."},{"key":"15355_CR27","doi-asserted-by":"publisher","first-page":"111762","DOI":"10.1016\/j.nut.2022.111762","volume":"103","author":"HS Yoo","year":"2022","unstructured":"Yoo, H. S., Shanmugalingam, U. & Smith, P. D. Potential roles of branched-chain amino acids in neurodegeneration. Nutrition 103, 111762 (2022).","journal-title":"Nutrition"},{"key":"15355_CR28","doi-asserted-by":"publisher","unstructured":"Griffin, J. W. & Bradshaw, P. C. Amino Acid Catabolism in Alzheimer\u2019s Disease Brain: Friend or Foe? Oxid. Med. Cell. Longev. 2017, 5472792. https:\/\/doi.org\/10.1155\/2017\/5472792 (2017).","DOI":"10.1155\/2017\/5472792"},{"key":"15355_CR29","doi-asserted-by":"publisher","first-page":"G602","DOI":"10.1152\/ajpgi.00230.2019","volume":"317","author":"CR Tiffany","year":"2019","unstructured":"Tiffany, C. R. & B\u00e4umler, A. J. Dysbiosis: from fiction to function. Am. J. Physiology-Gastrointestinal Liver Physiol. 317, G602\u2013G608 (2019).","journal-title":"Am. J. Physiology-Gastrointestinal Liver Physiol."},{"key":"15355_CR30","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1016\/j.jpba.2014.10.010","volume":"107","author":"R Gonz\u00e1lez-Dom\u00ednguez","year":"2015","unstructured":"Gonz\u00e1lez-Dom\u00ednguez, R., Garc\u00eda-Barrera, T. & G\u00f3mez-Ariza, J. L. Metabolite profiling for the identification of altered metabolic pathways in alzheimer\u2019s disease. J. Pharm. Biomed. Anal. 107, 75\u201381 (2015).","journal-title":"J. Pharm. Biomed. Anal."},{"key":"15355_CR31","doi-asserted-by":"publisher","first-page":"987","DOI":"10.4081\/cp.2017.987","volume":"7","author":"M Clapp","year":"2017","unstructured":"Clapp, M. et al. Gut microbiota\u2019s effect on mental health: the gut-brain axis. Clin. Pract. 7, 987. https:\/\/doi.org\/10.4081\/cp.2017.987 (2017).","journal-title":"Clin. Pract."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-15355-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-15355-4","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-15355-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,9]],"date-time":"2025-09-09T01:45:29Z","timestamp":1757382329000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-15355-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,15]]},"references-count":31,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["15355"],"URL":"https:\/\/doi.org\/10.1038\/s41598-025-15355-4","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,15]]},"assertion":[{"value":"16 January 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 August 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 August 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"29924"}}