TY - JOUR
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.
PY - 2016/8/31
Y1 - 2016/8/31
N2 - The pathway leading from beta-amyloid deposition to cognitive impairment is believed to be a cornerstone of the pathogenesis of Alzheimer’s disease (AD). However, what drives amyloid build-up in sporadic non-genetic 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 (i) GMB taxa with pro- and anti-inflammatory activity, and (ii) 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, IL-1β, IL-6, IL-18, IL-8, NLRP3, 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, HC). Amy+ patients showed higher levels of pro-inflammatory cytokines (IL-6, CXCL2, NLRP3 and IL-1β) compared to both controls and to Amy- patients. A reduction of the anti-inflammatory cytokine IL-10 was observed in Amy+ versus Amy-. Amy+ showed lower abundance of Eubacterium rectale and higher abundance of Escherichia/Shigella as compared to both HC (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 Eubacterium 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, Eubacterium 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 beta-amyloid deposition to cognitive impairment is believed to be a cornerstone of the pathogenesis of Alzheimer’s disease (AD). However, what drives amyloid build-up in sporadic non-genetic 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 (i) GMB taxa with pro- and anti-inflammatory activity, and (ii) 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, IL-1β, IL-6, IL-18, IL-8, NLRP3, 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, HC). Amy+ patients showed higher levels of pro-inflammatory cytokines (IL-6, CXCL2, NLRP3 and IL-1β) compared to both controls and to Amy- patients. A reduction of the anti-inflammatory cytokine IL-10 was observed in Amy+ versus Amy-. Amy+ showed lower abundance of Eubacterium rectale and higher abundance of Escherichia/Shigella as compared to both HC (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 Eubacterium 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, Eubacterium 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 - cognitive impairment
KW - brain amyloidosis
KW - inflammation
KW - gut microbiota
KW - neurodegeneration
U2 - 10.1016/j.neurobiolaging.2016.08.019
DO - 10.1016/j.neurobiolaging.2016.08.019
M3 - Article
SN - 0197-4580
JO - Neurobiology of Aging
JF - Neurobiology of Aging
ER -