Short-Chain Fatty Acids and Lipopolysaccharide as Mediators between Gut Dysbiosis and Amyloid Pathology in Alzheimer's Disease

Moira Marizzoni, Annamaria Cattaneo, Peppino Mirabelli, Cristina Festari, Nicola Lopizzo, Valentina Nicolosi, Elisa Mombelli, Monica Mazzelli, Delia Luongo, Daniele Naviglio, Luigi Coppola, Marco Salvatore, Giovanni B. Frisoni

Research output: Contribution to journalArticlepeer-review

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 < 0.001), pro-inflammatory cytokines (rho≥0.25, p≤0.012), and biomarkers of endothelial dysfunction (rho≥0.25, p≤0.042). In contrast, it was negatively correlated with butyrate (rho≤-0.42, p≤0.020) and the anti-inflammatory cytokine IL10 (rho≤-0.26, p≤0.009). Endothelial dysfunction was positively associated with pro-inflammatory cytokines, acetate and valerate (rho≥0.25, p≤0.045) and negatively with butyrate and IL10 levels (rho≤-0.25, p≤0.038). 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.

Original languageEnglish
Pages (from-to)683-697
Number of pages15
JournalJournal of Alzheimer's Disease
Volume78
Issue number2
DOIs
Publication statusPublished - 2020

Keywords

  • Brain amyloidosis
  • inflammation
  • lipopolysaccharide
  • microbiota
  • short chain fatty acids

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Psychology
  • Geriatrics and Gerontology
  • Psychiatry and Mental health

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