{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T16:00:44Z","timestamp":1785427244610,"version":"3.56.0"},"reference-count":25,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T00:00:00Z","timestamp":1783382400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"MEMOIR"},{"name":"European Union\u2019s Horizon 2020 research and innovation programme","award":["847468"],"award-info":[{"award-number":["847468"]}]},{"DOI":"10.13039\/501100004587","name":"Institute of Health Carlos III","doi-asserted-by":"publisher","award":["PI16\/01777"],"award-info":[{"award-number":["PI16\/01777"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"award":["PI16\/01777"],"award-info":[{"award-number":["PI16\/01777"]}],"id":[{"id":"https:\/\/ror.org\/00ca2c886","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Andalusian Regional Government","award":["PI-0055-2021"],"award-info":[{"award-number":["PI-0055-2021"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background\/Objectives: The gut\u2013brain axis and systemic metabolic dysregulation are increasingly implicated in Alzheimer\u2019s disease (AD) pathogenesis. This study aimed to characterize gut microbiota and plasma metabolomic profiles associated with amyloid pathology and cognitive impairment in patients with mild cognitive impairment (MCI). Methods: A cross-sectional multi-omics baseline analysis was performed in 47 MCI patients enrolled in a randomized, double-blind, crossover dietary intervention trial (NCT05029765). Gut microbiota composition was assessed by 16S rRNA sequencing (n = 47), and plasma metabolomics by untargeted LC-MS\/MS (n = 45 after exclusion of two PCA-defined metabolomic outliers). Patients were stratified according to plasma amyloid-beta 42\/40 ratio (BA42\/40) and ADAScog11 score, representing complementary biomarkers of amyloid burden and cognitive impairment, respectively. Results: Higher amyloid burden and worse cognitive performance were associated with significant gut microbiota alterations, including increased alpha diversity and distinct beta diversity profiles. Differential abundance analyses consistently showed enrichment of Bacteroides-associated taxa and Akkermansia, alongside depletion of short-chain fatty acid-producing genera such as Faecalibacterium, Blautia, and Phascolarctobacterium. Plasma metabolomics identified a coherent signature associated with elevated BA42\/40, characterized by accumulation of secondary bile acid sulfates and depletion of sphingolipids, neuroactive steroids, and anti-inflammatory lipid mediators, including pregnenolone sulfate, resolvin E1, and anandamide. A valid OPLS-DA discriminant model was obtained for BA42\/40, whereas no predictive model was achieved for ADAScog11. Critically, this dissociation, characterized by significant microbiota differences but no metabolomic separation for ADAScog11, is itself an informative finding, suggesting that gut microbiota dysbiosis and plasma metabolomic alterations are not equally coupled to both dimensions of MCI pathophysiology. Conclusions: MCI patients with greater amyloid pathology and cognitive impairment exhibited gut microbiota dysbiosis. However, metabolic associations were observed only for BA42\/40, but not for ADAScog11. These findings provide a mechanistic framework for evaluating the impact of Mediterranean diet and probiotic interventions in the longitudinal phase of the trial.<\/jats:p>","DOI":"10.3390\/nu18132200","type":"journal-article","created":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T08:04:49Z","timestamp":1783411489000},"page":"2200","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Gut Microbiota Composition and Plasma Metabolomic Profile Are Associated with Amyloid Pathology and Cognitive Performance in Patients with Mild Cognitive Impairment"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6662-2932","authenticated-orcid":false,"given":"Marina","family":"Mora-Ortiz","sequence":"first","affiliation":[{"name":"Lipids and Atherosclerosis Unit, Department of Internal Medicine, Reina Sofia University Hospital, 14004 Cordoba, Spain"},{"name":"Department of Medical and Surgical Sciences, Universidad de Cordoba, 14004 Cordoba, Spain"},{"name":"GC-09, Nutrigenomics and Metabolic Syndrome, Maimonides Institute of Biomedical Research of Cordoba (IMIBIC), 14004 Cordoba, Spain"},{"name":"Department of Cell Biology, Physiology and Immunology, Maimonides Institute of Biomedical Research of Cordoba (IMIBIC), University of Cordoba, 14004 Cordoba, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3541-2190","authenticated-orcid":false,"given":"Magdalena P.","family":"Cardelo","sequence":"additional","affiliation":[{"name":"Lipids and Atherosclerosis Unit, Department of Internal Medicine, Reina Sofia University Hospital, 14004 Cordoba, Spain"},{"name":"Department of Medical and Surgical Sciences, Universidad de Cordoba, 14004 Cordoba, Spain"},{"name":"GC-09, Nutrigenomics and Metabolic Syndrome, Maimonides Institute of Biomedical Research of Cordoba (IMIBIC), 14004 Cordoba, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esther","family":"Porras-P\u00e9rez","sequence":"additional","affiliation":[{"name":"Lipids and Atherosclerosis Unit, Department of Internal Medicine, Reina Sofia University Hospital, 14004 Cordoba, Spain"},{"name":"Department of Medical and Surgical Sciences, Universidad de Cordoba, 14004 Cordoba, Spain"},{"name":"GC-09, Nutrigenomics and Metabolic Syndrome, Maimonides Institute of Biomedical Research of Cordoba (IMIBIC), 14004 Cordoba, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alejandro","family":"Serr\u00e1n-Jim\u00e9nez","sequence":"additional","affiliation":[{"name":"Lipids and Atherosclerosis Unit, Department of Internal Medicine, Reina Sofia University Hospital, 14004 Cordoba, Spain"},{"name":"Department of Medical and Surgical Sciences, Universidad de Cordoba, 14004 Cordoba, Spain"},{"name":"GC-09, Nutrigenomics and Metabolic Syndrome, Maimonides Institute of Biomedical Research of Cordoba (IMIBIC), 14004 Cordoba, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4658-8212","authenticated-orcid":false,"given":"Carlos A.","family":"Ledesma-Escobar","sequence":"additional","affiliation":[{"name":"Department of Analytical Chemistry and Nanochemistry University Institute, Universidad de Cordoba, 14071 Cordoba, Spain"},{"name":"CIBER de Fragilidad y Envejecimiento Saludable (CIBERFES), Instituto de Salud Carlos III, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0697-719X","authenticated-orcid":false,"given":"Feliciano","family":"Priego-Capote","sequence":"additional","affiliation":[{"name":"Department of Analytical Chemistry and Nanochemistry University Institute, Universidad de Cordoba, 14071 Cordoba, Spain"},{"name":"CIBER de Fragilidad y Envejecimiento Saludable (CIBERFES), Instituto de Salud Carlos III, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3633-1146","authenticated-orcid":false,"given":"Cristina","family":"Conde-Gavil\u00e1n","sequence":"additional","affiliation":[{"name":"Neurology Service, Maimonides Institute for Biomedical Research in Cordoba (IMIBIC), Reina Sofia University Hospital, 14004 Cordoba, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8604-2054","authenticated-orcid":false,"given":"Eduardo","family":"Ag\u00fcera-Morales","sequence":"additional","affiliation":[{"name":"Neurology Service, Maimonides Institute for Biomedical Research in Cordoba (IMIBIC), Reina Sofia University Hospital, 14004 Cordoba, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafael","family":"Pineda Reyes","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Physiology and Immunology, Maimonides Institute of Biomedical Research of Cordoba (IMIBIC), University of Cordoba, 14004 Cordoba, Spain"},{"name":"CIBER Pathophysiology of Obesity and Nutrition (CIBEROBN), Carlos III Health Institute, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria M.","family":"Malagon","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Physiology and Immunology, Maimonides Institute of Biomedical Research of Cordoba (IMIBIC), University of Cordoba, 14004 Cordoba, Spain"},{"name":"CIBER Pathophysiology of Obesity and Nutrition (CIBEROBN), Carlos III Health Institute, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena M.","family":"Yubero-Serrano","sequence":"additional","affiliation":[{"name":"CIBER Pathophysiology of Obesity and Nutrition (CIBEROBN), Carlos III Health Institute, 28029 Madrid, Spain"},{"name":"Department of Food and Health, Fat Institute, Spanish National Research Council (CSIC), 41013 Seville, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0415-4184","authenticated-orcid":false,"given":"Antonio","family":"Camargo","sequence":"additional","affiliation":[{"name":"Lipids and Atherosclerosis Unit, Department of Internal Medicine, Reina Sofia University Hospital, 14004 Cordoba, Spain"},{"name":"Department of Medical and Surgical Sciences, Universidad de Cordoba, 14004 Cordoba, Spain"},{"name":"GC-09, Nutrigenomics and Metabolic Syndrome, Maimonides Institute of Biomedical Research of Cordoba (IMIBIC), 14004 Cordoba, Spain"},{"name":"CIBER Pathophysiology of Obesity and Nutrition (CIBEROBN), Carlos III Health Institute, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niki","family":"Katsiki","sequence":"additional","affiliation":[{"name":"Department of Nutritional Sciences and Dietetics, International Hellenic University, 57400 Thessaloniki, Greece"},{"name":"School of Medicine, European 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