Microbiota in neuroinflammation and synaptic dysfunction: a focus on Alzheimer’s disease

Abstract

Background The implication of gut microbiota in the control of brain functions in health and disease is a novel, currently emerging concept. Accumulating data suggest that the gut microbiota exert its action at least in part by modulating neuroinflammation. Given the link between neuroinflammatory changes and neuronal activity, it is plausible that gut microbiota may affect neuronal functions indirectly by impacting microglia, a key player in neuroinflammation. Indeed, increasing evidence suggests that interplay between microglia and synaptic dysfunction may involve microbiota, among other factors. In addition to these indirect microglia-dependent actions of microbiota on neuronal activity, it has been recently recognized that microbiota could also affect neuronal activity directly by stimulation of the vagus nerve. Main messages The putative mechanisms of the indirect and direct impact of microbiota on neuronal activity are discussed by focusing on Alzheimer’s disease, one of the most studied neurodegenerative disorders and the prime cause of dementia worldwide. More specifically, the mechanisms of microbiota-mediated microglial alterations are discussed in the context of the peripheral and central inflammation cross-talk. Next, we highlight the role of microbiota in the regulation of humoral mediators of peripheral immunity and their impact on vagus nerve stimulation. Finally, we address whether and how microbiota perturbations could affect synaptic neurotransmission and downstream cognitive dysfunction. Conclusions There is strong increasing evidence supporting a role for the gut microbiome in the pathogenesis of Alzheimer’s disease, including effects on synaptic dysfunction and neuroinflammation, which contribute to cognitive decline. Putative early intervention strategies based on microbiota modulation appear therapeutically promising for Alzheimer’s disease but still require further investigation.

Therapeutic roles of plants for 15 hypothesised causal bases of Alzheimer’s disease

“…Alterations in gut microbial communities in AD patients may result in pathophysiological changes in the brain [ 103 , 423 ]. This hypothesis is supported by evidence of decreased microbial diversity in the gut microbiome of AD patients [ 424 ]; an increase in pro-inflammatory gut bacterial taxa is associated with brain amyloid pathology in AD patients [ 425 ]; and mice raised with germ-free gut conditions have less cerebral amyloid deposition [ 426 ].…”

The Gut Microbiota-Brain Axis: A New Frontier on Neuropsychiatric Disorders

“…With age, microbiota suffers a reduction in the amount of Lactobacillus, Bifidobacteria, Bacteroidetes, Firmicutes, Lachnospiraceae, Ruminococcaceae, Coprococcus, Roseburia and Faecalibacterium, and an increase in the proportion of Odoribacter and Butyricimonas ( 37 – 39 ). Such changes are associated with gastrointestinal disorders that favor increased intestinal permeability, dysbiosis, and the development of a neuroinflammatory cascade ( Figure 1 ) ( 40 , 41 ).…”

“…For a recent review on the role of the microbiota in neuroinflammation and synaptic dysfunction in AD see, e.g., Bairamian et al ( 41 ).…”

GLP-1 Receptor Agonists in Neurodegeneration: Neurovascular Unit in the Spotlight

“…Another pertinent area for investigation would be the effects of GLP1-RAs on the gut microbiota, since alterations in the composition of gut microbiota or their metabolic products are reported in AD and PD cohorts [274,275]. This is relevant, since systemic metabolic disorders including T2DM affect the composition of gut microbiota [276,277], potentially leading to a milieu that is conducive to pathological processes relevant to neurodegeneration [274,275]. This aspect is also relevant, since there is an emerging notion that some CNS proteinopathies might originate in the periphery.…”