The Gut Microbiome and Alzheimer’s Disease: A Growing Relationship

Abstract

Evidence that the gut microbiota plays a key role in the pathogenesis of Alzheimer’s disease is already un-ravelling. The microbiota-gut-brain axis is a bidirectional communication system that is not fully understood but includes neural, immune, endocrine, and metabolic pathways. The progression of Alzheimer’s disease is supported by mechanisms related to the imbalance in the gut microbiota and the development of amyloid plaques in the brain, which are at the origin of Alzheimer's disease. Alterations in the composition of the gut microbiome led to dysregulation in the pathways governing this system. This leads to neurodegeneration through neuroinflammation and neurotransmitter dysregulation. Neurodegeneration and disruption of the blood-brain barrier are frontiers at the origin of Alzheimer’s disease. Furthermore, bacteria populating the gut microbiota can secrete large amounts of amyloid proteins and lipopolysaccharides, which modulate signaling pathways and alter the production of proinflammatory cytokines associated with the pathogenesis of Alz-heimer's disease. Importantly, through molecular mimicry, bacterial amyloids may elicit cross-seeding of misfolding and induce microglial priming at different levels of the brain-gut-microbiota axis. The potential mechanisms of amyloid spreading include neuron-to-neuron or distal neuron spreading, direct blood-brain barrier crossing, or via other cells such as astrocytes, fibroblasts, microglia, and immune system cells. Gut microbiota metabolites, including short-chain fatty acids, pro-inflammatory factors, and neurotransmitters may also affect AD pathogenesis and associated cognitive decline. The purpose of this review is to summarize and discuss the current findings that may elucidate the role of gut microbiota in the development of Alzheimer's disease. Understanding the underlying mechanisms may provide new insights into novel therapeutic strategies for Alzheimer's disease, such as probiotics and targeted oligosaccharides.

Exploring the Influence of Gut–Brain Axis Modulation on Cognitive Health: A Comprehensive Review of Prebiotics, Probiotics, and Symbiotics

“…The development of Alzheimer’s disease [ 69 , 88 , 89 , 90 , 91 , 92 , 93 , 94 , 95 , 96 , 97 , 98 , 99 , 100 , 101 , 102 , 103 , 104 , 105 , 106 , 107 ] and the mechanisms through which the microbiome can contribute to the progression of Alzheimer’s disease have been investigated [ 108 , 109 , 110 , 111 , 112 , 113 , 114 , 115 , 116 , 117 , 118 , 119 , 120 , 121 , 122 , 123 , 124 , 125 , 126 , 127 , 128 , 129 , 130 , 131 , 132 , 133 , 134 , 135 , 136 , 137 , 138 ]. Numerous studies are also available regarding treatments with probiotics […”

Interactions and Insertion of Escherichia coli Hfq into Outer Membrane Vesicles as Revealed by Infrared and Orientated Circular Dichroism Spectroscopies

“…Finally, it is intriguing that OMVs of different bacteria were proposed as possible factors involved in the development of Alzheimer's disease and other neurodegenerative disorders [57,58]. Moreover, it was suggested that bacterial amyloid-like proteins may stimulate human/animal β-amyloid accumulation by mechanisms involving the cross-seeding of misfolded proteins due to molecular mimicry [59]. Since Hfq contains the amyloid-like domain, one could speculate that its inclusion in OMVs produced by gut bacteria, like E. coli, might be an especially important risk factor for stimulating the development of neurodegenerative diseases in animals and humans.…”

Renale Amyloidosen

“…Die kausale Therapie zielt auf die Elimination des pathologischen Plasmazellklons ab und liegt, bedingt durch die komplexen neueren Therapieschemata, meist in den Händen der Hämatoonkologie 25 . Die teils ausgeprägte Proteinurie ist therapeutisch nur schwer zu beeinflussen.…”