Starved synapses: Gut microbiome dysbiosis and its role in Alzheimer's glucose impairment.

Abstract

Alzheimer's disease (AD) is increasingly recognised as a multifactorial disorder driven by metabolic, microbial, and neuroinflammatory imbalances. The study of the research results proposes that gut dysbiosis and impaired brain glucose metabolism are closely interrelated through the gut-brain metabolism axis. Changes in the intestinal microbiome may disrupt insulin sensitivity, cause systemic inflammation, and disrupt the blood-brain barrier, worsening neuronal glucose deficits and facilitating amyloid-β (Aβ) aggregation and tau phosphorylation. Alongside, neurodegenerative cascades are further enhanced by neuronal metabolic reprogramming, characterised by decreased glucose uptake, dysfunctional glycolytic enzymes, and oxidative stress. Short-chain fatty acids (SCFAs) are mainly butyrate, which have a neuroprotective effect in regulating inflammation and gut integrity, and dysbiosis causes increased pro-inflammatory cytokines and endotoxin leakage. This two-way communication network provides new therapeutic opportunities, such as probiotics, prebiotics, nutritional control, and metabolic reprogramming interventions, to regain homeostasis and prevent the advancement of AD.