Title | Short-Chain Fatty Acids and Lipopolysaccharide as Mediators Between Gut Dysbiosis and Amyloid Pathology in Alzheimer's Disease. |
Publication Type | Journal Article |
Year of Publication | 2020 |
Authors | Marizzoni, M, Cattaneo, A, Mirabelli, P, Festari, C, Lopizzo, N, Nicolosi, V, Mombelli, E, Mazzelli, M, Luongo, D, Naviglio, D, Coppola, L, Salvatore, M, Frisoni, GB |
Journal | J Alzheimers Dis |
Volume | 78 |
Issue | 2 |
Pagination | 683-697 |
Date Published | 2020 |
ISSN | 1875-8908 |
Abstract | BACKGROUND: Metagenomic data support an association between certain bacterial strains and Alzheimer's disease (AD), but their functional dynamics remain elusive. OBJECTIVE: To investigate the association between amyloid pathology, bacterial products such as lipopolysaccharide (LPS) and short chain fatty acids (SCFAs: acetate, valerate, butyrate), inflammatory mediators, and markers of endothelial dysfunction in AD. METHODS: Eighty-nine older persons with cognitive performance from normal to dementia underwent florbetapir amyloid PET and blood collection. Brain amyloidosis was measured with standardized uptake value ratio versus cerebellum. Blood levels of LPS were measured by ELISA, SCFAs by mass spectrometry, cytokines by using real-time PCR, and biomarkers of endothelial dysfunction by flow cytometry. We investigated the association between the variables listed above with Spearman's rank test. RESULTS: Amyloid SUVR uptake was positively associated with blood LPS (rho≥0.32, p≤0.006), acetate and valerate (rho≥0.45, p CONCLUSION: We report a novel association between gut microbiota-related products and systemic inflammation with brain amyloidosis via endothelial dysfunction, suggesting that SCFAs and LPS represent candidate pathophysiologic links between the gut microbiota and AD pathology. |
DOI | 10.3233/JAD-200306 |
Alternate Journal | J Alzheimers Dis |
PubMed ID | 33074224 |