4.5 Review

The Gut Microbiota and Alzheimer's Disease

Journal

JOURNAL OF ALZHEIMERS DISEASE
Volume 58, Issue 1, Pages 1-15

Publisher

IOS PRESS
DOI: 10.3233/JAD-161141

Keywords

Aging; Alzheimer's disease; amyloid; amyloid beta-peptides; blood-brain barrier; dysbiosis; gut microbiota; lipopolysaccharides; obesity; type 2 diabetes mellitus

Categories

Funding

  1. National Nature Science Foundation of China [81271214, 81400986]
  2. Natural Science Foundation of Guangdong Province [2014A030313541]
  3. Science and Technology Planning Project of Zhanjiang [2014A01031]
  4. Dongguan international science and technology cooperation project [2013508152012]
  5. Affiliated Hospital of Guangdong Medical College

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The gut microbiota comprises a complex community of microorganism species that resides in our gastrointestinal ecosystem and whose alterations influence not only various gut disorders but also central nervous system disorders such as Alzheimer's disease (AD). AD, the most common form of dementia, is a neurodegenerative disorder associated with impaired cognition and cerebral accumulation of amyloid-beta peptides (A beta). Most notably, the microbiota-gut-brain axis is a bidirectional communication system that is not fully understood, but includes neural, immune, endocrine, and metabolic pathways. Studies in germ-free animals and in animals exposed to pathogenic microbial infections, antibiotics, probiotics, or fecal microbiota transplantation suggest a role for the gut microbiota in host cognition or AD-related pathogenesis. The increased permeability of the gut and blood-brain barrier induced by microbiota dysbiosis may mediate or affect AD pathogenesis and other neurodegenerative disorders, especially those associated with aging. In addition, bacteria populating the gut microbiota can secrete large amounts of amyloids and lipopolysaccharides, which might contribute to the modulation of signaling pathways and the production of proinflammatory cytokines associated with the pathogenesis of AD. Moreover, imbalances in the gut microbiota can induce inflammation that is associated with the pathogenesis of obesity, type 2 diabetes mellitus, and AD. The purpose of this review is to summarize and discuss the current findings that may elucidate the role of the gut microbiota in the development of AD. Understanding the underlying mechanisms may provide new insights into novel therapeutic strategies for AD.

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