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

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• 作者：Annamaria Cattaneo^a ; ^b ; ^{acattaneo@fatebenefratelli.eu} ; Nadia Cattane^a ; Samantha Galluzzi^c ; Stefania Provasi^a ; Nicola Lopizzo^a ; Cristina Festari^c ; Clarissa Ferrari^a ; Ugo Paolo Guerra^d ; Barbara Paghera^e ; Cristina Muscio^a ; ^f ; Angelo Bianchetti^g ; Giorgio Dalla Volta^h ; Marinella Turlaⁱ ; Maria Sofia Cotelliⁱ ; Michele Gennuso^j ; Alessandro Prelle^j ; Orazio Zanetti^a ; Giulia Lussignoli^a ; Dario Mirabile^f ; Daniele Bellandi^k ; Simona Gentile^l ; Gloria Belotti^m ; Daniele Villaniⁿ ; Taoufiq Harach^o ; Tristan Bolmont^p ; Alessandro Padovani^q ; Marina Boccardi^c ; Giovanni B. Frisoni^c ; ^r ; ^s ; for the INDIA-FBP Group¹
• 关键词：Cognitive impairment ; Brain amyloidosis ; Inflammation ; Gut microbiota ; Neurodegeneration
• 刊名：Neurobiology of Aging
• 出版年：2017
• 出版时间：January 2017
• 年：2017
• 卷：49
• 期：Complete
• 页码：60-68
• 全文大小：972 K
• 卷排序：49

文摘

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.