Journal article
Short-Chain Fatty Acids and Lipopolysaccharide as Mediators Between Gut Dysbiosis and Amyloid Pathology in Alzheimer's Disease.
- Marizzoni M Laboratory of Neuroimaging and Alzheimer's Epidemiology, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy.
- Cattaneo A Laboratory of Biological Psychiatry, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy.
- Mirabelli P IRCCS SDN, Naples, Italy.
- Festari C Laboratory of Neuroimaging and Alzheimer's Epidemiology, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy.
- Lopizzo N Laboratory of Biological Psychiatry, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy.
- Nicolosi V Laboratory of Neuroimaging and Alzheimer's Epidemiology, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy.
- Mombelli E Laboratory of Biological Psychiatry, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy.
- Mazzelli M Laboratory of Biological Psychiatry, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy.
- Luongo D I.B.B.- CNR Via Mezzocannone, Naples, Italy.
- Naviglio D Department of Chemical Sciences, University of Naples Federico II, Via Cintia 4, Naples, Italy.
- Coppola L IRCCS SDN, Naples, Italy.
- Salvatore M IRCCS SDN, Naples, Italy.
- Frisoni GB Memory Clinic and LANVIE - Laboratory of Neuroimaging of Aging, University Hospitals and University of Geneva, Geneva, Switzerland.
- 2020-10-19
Published in:
- Journal of Alzheimer's disease : JAD. - 2020
English
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.
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.
- Language
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- English
- Open access status
- closed
- Identifiers
-
- DOI 10.3233/JAD-200306
- PMID 33074224
- Persistent URL
- https://sonar.ch/global/documents/194665
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