Association of brain amyloidosis with pro-inflammatory gut bacterial taxa and peripheral inflammation markers in cognitively impaired elderly

Annamaria Cattaneo, Nadia Cattane, Samantha Galluzzi, Stefania Provasi, Nicola Lopizzo, Cristina Festari, Clarissa Ferrari, Ugo Paolo Guerra, Barbara Paghera, Cristina Muscio, Angelo Bianchetti, Giorgio Dalla Volta, Marinella Turla, Maria Sofia Cotelli, Michele Gennuso, Alessandro Prelle, Orazio Zanetti, Giulia Lussignoli, Dario Mirabile, Daniele BellandiSimona Gentile, Gloria Belotti, Daniele Villani, Taoufiq Harach, Tristan Bolmont, Alessandro Padovani, Marina Boccardi, Giovanni B Frisoni, INDIA-FBP Group

Research output: Contribution to journalArticle

Abstract

The pathway leading from amyloid-β deposition to cognitive impairment is believed to be a cornerstone of the pathogenesis of Alzheimer's disease (AD). However, what drives amyloid buildup in sporadic nongenetic cases of AD is still unknown. AD brains feature an inflammatory reaction around amyloid plaques, and a specific subset of the gut microbiota (GMB) may promote brain inflammation. We investigated the possible role of the GMB in AD pathogenesis by studying the association of brain amyloidosis with (1) GMB taxa with pro- and anti-inflammatory activity; and (2) peripheral inflammation in cognitively impaired patients. We measured the stool abundance of selected bacterial GMB taxa (Escherichia/Shigella, Pseudomonas aeruginosa, Eubacterium rectale, Eubacterium hallii, Faecalibacterium prausnitzii, and Bacteroides fragilis) and the blood expression levels of cytokines (pro-inflammatory cytokines: CXCL2, CXCL10, interleukin [IL]-1β, IL-6, IL-18, IL-8, inflammasome complex (NLRP3), tumor necrosis factor-alpha [TNF-α]; anti-inflammatory cytokines: IL-4, IL-10, IL-13) in cognitively impaired patients with (n = 40, Amy+) and with no brain amyloidosis (n = 33, Amy-) and also in a group of controls (n = 10, no brain amyloidosis and no cognitive impairment). Amy+ patients showed higher levels of pro-inflammatory cytokines (IL-6, CXCL2, NLRP3, and IL-1β) compared with both controls and with Amy- patients. A reduction of the anti-inflammatory cytokine IL-10 was observed in Amy+ versus Amy-. Amy+ showed lower abundance of E. rectale and higher abundance of Escherichia/Shigella compared with both healthy controls (fold change, FC = -9.6, p < 0.001 and FC = +12.8, p < 0.001, respectively) and to Amy- (FC = -7.7, p < 0.001 and FC = +7.4, p = 0.003). A positive correlation was observed between pro-inflammatory cytokines IL-1β, NLRP3, and CXCL2 with abundance of the inflammatory bacteria taxon Escherichia/Shigella (rho = 0.60, p < 0.001; rho = 0.57, p < 0.001; and rho = 0.30, p = 0.007, respectively) and a negative correlation with the anti-inflammatory E. rectale (rho = -0.48, p < 0.001; rho = -0.25, p = 0.024; rho = -0.49, p < 0.001). Our data indicate that an increase in the abundance of a pro-inflammatory GMB taxon, Escherichia/Shigella, and a reduction in the abundance of an anti-inflammatory taxon, E. rectale, are possibly associated with a peripheral inflammatory state in patients with cognitive impairment and brain amyloidosis. A possible causal relation between GMB-related inflammation and amyloidosis deserves further investigation.

Original languageEnglish
Number of pages9
JournalNeurobiology of Aging
DOIs
Publication statusE-pub ahead of print - Aug 31 2016

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Amyloidosis
Escherichia
Shigella
Cytokines
Inflammation
Anti-Inflammatory Agents
Alzheimer Disease
Brain
Interleukin-1
Eubacterium
Amyloid
Interleukin-10
Interleukin-6
Inflammasomes
Bacteroides fragilis
Interleukin-18
Interleukin-13
Amyloid Plaques
Encephalitis
Interleukin-8

Keywords

  • Journal Article

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Association of brain amyloidosis with pro-inflammatory gut bacterial taxa and peripheral inflammation markers in cognitively impaired elderly. / Cattaneo, Annamaria; Cattane, Nadia; Galluzzi, Samantha; Provasi, Stefania; Lopizzo, Nicola; Festari, Cristina; Ferrari, Clarissa; Guerra, Ugo Paolo; Paghera, Barbara; Muscio, Cristina; Bianchetti, Angelo; Volta, Giorgio Dalla; Turla, Marinella; Cotelli, Maria Sofia; Gennuso, Michele; Prelle, Alessandro; Zanetti, Orazio; Lussignoli, Giulia; Mirabile, Dario; Bellandi, Daniele; Gentile, Simona; Belotti, Gloria; Villani, Daniele; Harach, Taoufiq; Bolmont, Tristan; Padovani, Alessandro; Boccardi, Marina; Frisoni, Giovanni B; INDIA-FBP Group.

In: Neurobiology of Aging, 31.08.2016.

Research output: Contribution to journalArticle

Cattaneo, A, Cattane, N, Galluzzi, S, Provasi, S, Lopizzo, N, Festari, C, Ferrari, C, Guerra, UP, Paghera, B, Muscio, C, Bianchetti, A, Volta, GD, Turla, M, Cotelli, MS, Gennuso, M, Prelle, A, Zanetti, O, Lussignoli, G, Mirabile, D, Bellandi, D, Gentile, S, Belotti, G, Villani, D, Harach, T, Bolmont, T, Padovani, A, Boccardi, M, Frisoni, GB & INDIA-FBP Group 2016, 'Association of brain amyloidosis with pro-inflammatory gut bacterial taxa and peripheral inflammation markers in cognitively impaired elderly', Neurobiology of Aging. https://doi.org/10.1016/j.neurobiolaging.2016.08.019
Cattaneo, Annamaria ; Cattane, Nadia ; Galluzzi, Samantha ; Provasi, Stefania ; Lopizzo, Nicola ; Festari, Cristina ; Ferrari, Clarissa ; Guerra, Ugo Paolo ; Paghera, Barbara ; Muscio, Cristina ; Bianchetti, Angelo ; Volta, Giorgio Dalla ; Turla, Marinella ; Cotelli, Maria Sofia ; Gennuso, Michele ; Prelle, Alessandro ; Zanetti, Orazio ; Lussignoli, Giulia ; Mirabile, Dario ; Bellandi, Daniele ; Gentile, Simona ; Belotti, Gloria ; Villani, Daniele ; Harach, Taoufiq ; Bolmont, Tristan ; Padovani, Alessandro ; Boccardi, Marina ; Frisoni, Giovanni B ; INDIA-FBP Group. / Association of brain amyloidosis with pro-inflammatory gut bacterial taxa and peripheral inflammation markers in cognitively impaired elderly. In: Neurobiology of Aging. 2016.
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abstract = "The pathway leading from amyloid-β deposition to cognitive impairment is believed to be a cornerstone of the pathogenesis of Alzheimer's disease (AD). However, what drives amyloid buildup in sporadic nongenetic cases of AD is still unknown. AD brains feature an inflammatory reaction around amyloid plaques, and a specific subset of the gut microbiota (GMB) may promote brain inflammation. We investigated the possible role of the GMB in AD pathogenesis by studying the association of brain amyloidosis with (1) GMB taxa with pro- and anti-inflammatory activity; and (2) peripheral inflammation in cognitively impaired patients. We measured the stool abundance of selected bacterial GMB taxa (Escherichia/Shigella, Pseudomonas aeruginosa, Eubacterium rectale, Eubacterium hallii, Faecalibacterium prausnitzii, and Bacteroides fragilis) and the blood expression levels of cytokines (pro-inflammatory cytokines: CXCL2, CXCL10, interleukin [IL]-1β, IL-6, IL-18, IL-8, inflammasome complex (NLRP3), tumor necrosis factor-alpha [TNF-α]; anti-inflammatory cytokines: IL-4, IL-10, IL-13) in cognitively impaired patients with (n = 40, Amy+) and with no brain amyloidosis (n = 33, Amy-) and also in a group of controls (n = 10, no brain amyloidosis and no cognitive impairment). Amy+ patients showed higher levels of pro-inflammatory cytokines (IL-6, CXCL2, NLRP3, and IL-1β) compared with both controls and with Amy- patients. A reduction of the anti-inflammatory cytokine IL-10 was observed in Amy+ versus Amy-. Amy+ showed lower abundance of E. rectale and higher abundance of Escherichia/Shigella compared with both healthy controls (fold change, FC = -9.6, p < 0.001 and FC = +12.8, p < 0.001, respectively) and to Amy- (FC = -7.7, p < 0.001 and FC = +7.4, p = 0.003). A positive correlation was observed between pro-inflammatory cytokines IL-1β, NLRP3, and CXCL2 with abundance of the inflammatory bacteria taxon Escherichia/Shigella (rho = 0.60, p < 0.001; rho = 0.57, p < 0.001; and rho = 0.30, p = 0.007, respectively) and a negative correlation with the anti-inflammatory E. rectale (rho = -0.48, p < 0.001; rho = -0.25, p = 0.024; rho = -0.49, p < 0.001). Our data indicate that an increase in the abundance of a pro-inflammatory GMB taxon, Escherichia/Shigella, and a reduction in the abundance of an anti-inflammatory taxon, E. rectale, are possibly associated with a peripheral inflammatory state in patients with cognitive impairment and brain amyloidosis. A possible causal relation between GMB-related inflammation and amyloidosis deserves further investigation.",
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T1 - Association of brain amyloidosis with pro-inflammatory gut bacterial taxa and peripheral inflammation markers in cognitively impaired elderly

AU - Cattaneo, Annamaria

AU - Cattane, Nadia

AU - Galluzzi, Samantha

AU - Provasi, Stefania

AU - Lopizzo, Nicola

AU - Festari, Cristina

AU - Ferrari, Clarissa

AU - Guerra, Ugo Paolo

AU - Paghera, Barbara

AU - Muscio, Cristina

AU - Bianchetti, Angelo

AU - Volta, Giorgio Dalla

AU - Turla, Marinella

AU - Cotelli, Maria Sofia

AU - Gennuso, Michele

AU - Prelle, Alessandro

AU - Zanetti, Orazio

AU - Lussignoli, Giulia

AU - Mirabile, Dario

AU - Bellandi, Daniele

AU - Gentile, Simona

AU - Belotti, Gloria

AU - Villani, Daniele

AU - Harach, Taoufiq

AU - Bolmont, Tristan

AU - Padovani, Alessandro

AU - Boccardi, Marina

AU - Frisoni, Giovanni B

AU - INDIA-FBP Group

N1 - Copyright © 2016 Elsevier Inc. All rights reserved.

PY - 2016/8/31

Y1 - 2016/8/31

N2 - The pathway leading from amyloid-β deposition to cognitive impairment is believed to be a cornerstone of the pathogenesis of Alzheimer's disease (AD). However, what drives amyloid buildup in sporadic nongenetic cases of AD is still unknown. AD brains feature an inflammatory reaction around amyloid plaques, and a specific subset of the gut microbiota (GMB) may promote brain inflammation. We investigated the possible role of the GMB in AD pathogenesis by studying the association of brain amyloidosis with (1) GMB taxa with pro- and anti-inflammatory activity; and (2) peripheral inflammation in cognitively impaired patients. We measured the stool abundance of selected bacterial GMB taxa (Escherichia/Shigella, Pseudomonas aeruginosa, Eubacterium rectale, Eubacterium hallii, Faecalibacterium prausnitzii, and Bacteroides fragilis) and the blood expression levels of cytokines (pro-inflammatory cytokines: CXCL2, CXCL10, interleukin [IL]-1β, IL-6, IL-18, IL-8, inflammasome complex (NLRP3), tumor necrosis factor-alpha [TNF-α]; anti-inflammatory cytokines: IL-4, IL-10, IL-13) in cognitively impaired patients with (n = 40, Amy+) and with no brain amyloidosis (n = 33, Amy-) and also in a group of controls (n = 10, no brain amyloidosis and no cognitive impairment). Amy+ patients showed higher levels of pro-inflammatory cytokines (IL-6, CXCL2, NLRP3, and IL-1β) compared with both controls and with Amy- patients. A reduction of the anti-inflammatory cytokine IL-10 was observed in Amy+ versus Amy-. Amy+ showed lower abundance of E. rectale and higher abundance of Escherichia/Shigella compared with both healthy controls (fold change, FC = -9.6, p < 0.001 and FC = +12.8, p < 0.001, respectively) and to Amy- (FC = -7.7, p < 0.001 and FC = +7.4, p = 0.003). A positive correlation was observed between pro-inflammatory cytokines IL-1β, NLRP3, and CXCL2 with abundance of the inflammatory bacteria taxon Escherichia/Shigella (rho = 0.60, p < 0.001; rho = 0.57, p < 0.001; and rho = 0.30, p = 0.007, respectively) and a negative correlation with the anti-inflammatory E. rectale (rho = -0.48, p < 0.001; rho = -0.25, p = 0.024; rho = -0.49, p < 0.001). Our data indicate that an increase in the abundance of a pro-inflammatory GMB taxon, Escherichia/Shigella, and a reduction in the abundance of an anti-inflammatory taxon, E. rectale, are possibly associated with a peripheral inflammatory state in patients with cognitive impairment and brain amyloidosis. A possible causal relation between GMB-related inflammation and amyloidosis deserves further investigation.

AB - The pathway leading from amyloid-β deposition to cognitive impairment is believed to be a cornerstone of the pathogenesis of Alzheimer's disease (AD). However, what drives amyloid buildup in sporadic nongenetic cases of AD is still unknown. AD brains feature an inflammatory reaction around amyloid plaques, and a specific subset of the gut microbiota (GMB) may promote brain inflammation. We investigated the possible role of the GMB in AD pathogenesis by studying the association of brain amyloidosis with (1) GMB taxa with pro- and anti-inflammatory activity; and (2) peripheral inflammation in cognitively impaired patients. We measured the stool abundance of selected bacterial GMB taxa (Escherichia/Shigella, Pseudomonas aeruginosa, Eubacterium rectale, Eubacterium hallii, Faecalibacterium prausnitzii, and Bacteroides fragilis) and the blood expression levels of cytokines (pro-inflammatory cytokines: CXCL2, CXCL10, interleukin [IL]-1β, IL-6, IL-18, IL-8, inflammasome complex (NLRP3), tumor necrosis factor-alpha [TNF-α]; anti-inflammatory cytokines: IL-4, IL-10, IL-13) in cognitively impaired patients with (n = 40, Amy+) and with no brain amyloidosis (n = 33, Amy-) and also in a group of controls (n = 10, no brain amyloidosis and no cognitive impairment). Amy+ patients showed higher levels of pro-inflammatory cytokines (IL-6, CXCL2, NLRP3, and IL-1β) compared with both controls and with Amy- patients. A reduction of the anti-inflammatory cytokine IL-10 was observed in Amy+ versus Amy-. Amy+ showed lower abundance of E. rectale and higher abundance of Escherichia/Shigella compared with both healthy controls (fold change, FC = -9.6, p < 0.001 and FC = +12.8, p < 0.001, respectively) and to Amy- (FC = -7.7, p < 0.001 and FC = +7.4, p = 0.003). A positive correlation was observed between pro-inflammatory cytokines IL-1β, NLRP3, and CXCL2 with abundance of the inflammatory bacteria taxon Escherichia/Shigella (rho = 0.60, p < 0.001; rho = 0.57, p < 0.001; and rho = 0.30, p = 0.007, respectively) and a negative correlation with the anti-inflammatory E. rectale (rho = -0.48, p < 0.001; rho = -0.25, p = 0.024; rho = -0.49, p < 0.001). Our data indicate that an increase in the abundance of a pro-inflammatory GMB taxon, Escherichia/Shigella, and a reduction in the abundance of an anti-inflammatory taxon, E. rectale, are possibly associated with a peripheral inflammatory state in patients with cognitive impairment and brain amyloidosis. A possible causal relation between GMB-related inflammation and amyloidosis deserves further investigation.

KW - Journal Article

U2 - 10.1016/j.neurobiolaging.2016.08.019

DO - 10.1016/j.neurobiolaging.2016.08.019

M3 - Article

C2 - 27776263

JO - Neurobiology of Aging

JF - Neurobiology of Aging

SN - 0197-4580

ER -