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

Article Article scientifique Article Association of brain amyloidosis with pro-inflammatory gut bacterial taxa and peripheral inflammation markers in cognitively impaired elderly eng 2016 author Cattaneo Annamaria author Cattane Nadia author Galluzzi Samantha author Provasi Stefania author Lopizzo Nicola author Festari Cristina author Ferrari Clarissa author Guerra Ugo Paolo author Paghera Barbara author Muscio Cristina author Bianchetti Angelo author Volta Giorgio Dalla author Turla Marinella author Cotelli Maria Sofia author Gennuso Michele author Prelle Alessandro author Zanetti Orazio author Lussignoli Giulia author Mirabile Dario author Bellandi Daniele author Gentile Simona author Belotti Gloria author Villani Daniele author Harach Taoufiq author Bolmont Tristan 864457 author Padovani Alessandro author Boccardi Marina 850343 author Frisoni Giovanni 810190 60-68 10.1016/j.neurobiolaging.2016.08.019 27776263 0197-4580 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. Cognitive impairment Brain amyloidosis Inflammation Gut microbiota Neurodegeneration Dewey 616.89 60 Département de psychiatrie 225 false 853 Troubles de mémoire et maladie d'Alzeimer 935 Neurobiology of aging 49 f6b79b58-0bde-4d01-8d3b-93fead55a29f Article (Published version) Restricted Cattaneo_NBA2016.pdf 890732 application/pdf restrictedAccess Faculté de médecine / Section de médecine clinique / Département de psychiatrie

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Association of brain amyloidosis with pro-inflammatory gut bacterial taxa and peripheral inflammation markers in cognitively impaired elderly	Neurobiology of aging			2016	769	3

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