{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T00:10:30Z","timestamp":1790727030801,"version":"4.1.0"},"reference-count":68,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2022,11,5]],"date-time":"2022-11-05T00:00:00Z","timestamp":1667606400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale (INSERM), the Institut de Sant\u00e9 Publique, Epid\u00e9miologie et D\u00e9veloppement of the University of Bordeaux and Sanofi-Aventis"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>The gut microbiome is involved in nutrient metabolism and produces metabolites that, via the gut\u2013brain axis, signal to the brain and influence cognition. Human studies have so far had limited success in identifying early metabolic alterations linked to cognitive aging, likely due to limitations in metabolite coverage or follow-ups. Older persons from the Three-City population-based cohort who had not been diagnosed with dementia at the time of blood sampling were included, and repeated measures of cognition over 12 subsequent years were collected. Using a targeted metabolomics platform, we identified 72 circulating gut-derived metabolites in a case\u2013control study on cognitive decline, nested within the cohort (discovery n = 418; validation n = 420). Higher serum levels of propionic acid, a short-chain fatty acid, were associated with increased odds of cognitive decline (OR for 1 SD = 1.40 (95% CI 1.11, 1.75) for discovery and 1.26 (1.02, 1.55) for validation). Additional analyses suggested mediation by hypercholesterolemia and diabetes. Propionic acid strongly correlated with blood glucose (r = 0.79) and with intakes of meat and cheese (r &gt; 0.15), but not fiber (r = 0.04), suggesting a minor role of prebiotic foods per se, but a possible link to processed foods, in which propionic acid is a common preservative. The adverse impact of propionic acid on metabolism and cognition deserves further investigation.<\/jats:p>","DOI":"10.3390\/nu14214688","type":"journal-article","created":{"date-parts":[[2022,11,7]],"date-time":"2022-11-07T03:02:22Z","timestamp":1667790142000},"page":"4688","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":45,"title":["Exploration of the Gut\u2013Brain Axis through Metabolomics Identifies Serum Propionic Acid Associated with Higher Cognitive Decline in Older Persons"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3667-6948","authenticated-orcid":false,"given":"Jeanne","family":"Neuffer","sequence":"first","affiliation":[{"name":"Bordeaux Population Health Research Center, University of Bordeaux, INSERMUMR 1219, F-33000 Bordeaux, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7640-8833","authenticated-orcid":false,"given":"Ra\u00fal","family":"Gonz\u00e1lez-Dom\u00ednguez","sequence":"additional","affiliation":[{"name":"Nutrition, Food Science and Gastronomy Department, Food Innovation Network (XIA), Institute of Nutrition and Food Safety (INSA-UB), Faculty of Pharmacy and Food Science, University of Barcelona, 08028 Barcelona, Spain"},{"name":"CIBER Fragilidad y Envejecimiento Saludable (CIBERFES), Instituto de Salud Carlos III, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7857-6697","authenticated-orcid":false,"given":"Sophie","family":"Lef\u00e8vre-Arbogast","sequence":"additional","affiliation":[{"name":"Bordeaux Population Health Research Center, University of Bordeaux, INSERMUMR 1219, F-33000 Bordeaux, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7742-3189","authenticated-orcid":false,"given":"Dorrain Y.","family":"Low","sequence":"additional","affiliation":[{"name":"Human Nutrition Unit, Universit\u00e9 Clermont Auvergne, INRAEUMR1019, F-63000 Clermont Ferrand, France"},{"name":"Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore 636921, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B\u00e9n\u00e9dicte","family":"Driollet","sequence":"additional","affiliation":[{"name":"Bordeaux Population Health Research Center, University of Bordeaux, INSERMUMR 1219, F-33000 Bordeaux, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5169-7421","authenticated-orcid":false,"given":"Catherine","family":"Helmer","sequence":"additional","affiliation":[{"name":"Bordeaux Population Health Research Center, University of Bordeaux, INSERMUMR 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R.","family":"Ruigrok","sequence":"additional","affiliation":[{"name":"Brain Plasticity Group, Swammerdam Institute for Life Sciences, University of Amsterdam, 1098 XH Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3669-5206","authenticated-orcid":false,"given":"Barbara","family":"Altendorfer","sequence":"additional","affiliation":[{"name":"Institute of Molecular Regenerative Medicine, Spinal Cord Injury and Tissue Regeneration Center Salzburg, Paracelsus Medical University, 5020 Salzburg, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1653-8046","authenticated-orcid":false,"given":"Ludwig","family":"Aigner","sequence":"additional","affiliation":[{"name":"Institute of Molecular Regenerative Medicine, Spinal Cord Injury and Tissue Regeneration Center Salzburg, Paracelsus Medical University, 5020 Salzburg, 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Wohl Clinical Neuroscience Institute, Institute of Psychiatry, Psychology and Neuroscience, King\u2019s College London, London SE5 9NU, UK"},{"name":"Department of Neurology, University Hospital Carl Gustav Carus, Technische Universit\u00e4t Dresden, 01307 Dresden, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudine","family":"Manach","sequence":"additional","affiliation":[{"name":"Human Nutrition Unit, Universit\u00e9 Clermont Auvergne, INRAEUMR1019, F-63000 Clermont Ferrand, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3095-4254","authenticated-orcid":false,"given":"Merc\u00e8","family":"Pall\u00e0s","sequence":"additional","affiliation":[{"name":"Pharmacology Section, Department of Pharmacology, Toxicology and Medicinal Chemistry, Faculty of Pharmacy and Food Sciences, and Institute of Neurociencies, University of Barcelona, 08028 Barcelona, 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