Microbiome Engineering for Biotherapeutic in Alzheimer’s Disease Through the Gut–Brain Axis: Potentials and Limitations

Abstract

Alzheimer's disease (AD) is a neurodegenerative condition characterized by considerable cognitive decline and functional impairment, primarily due to the progressive alteration of neurons, microglia, and astrocytes. Pathological manifestations of AD include the loss of synaptic plasticity, reduction in synaptic strength by amyloid-beta, aggregation, and neurotoxicity from tau protein post-translational modifications, all contributing to the disruption of neural networks. Despite its current pharmacological treatment for AD, different approaches to treat such disease are being developed, from a microbiome perspective. The microbiome encompasses a diverse microorganism, including beneficial bacteria that create a positive impact to diminish AD pathogenesis. Growing evidence suggests that probiotic, prebiotic, synbiotic, and postbiotics can positively modulate the gut-brain axis, reducing systemic inflammation, restoring neurotransmitter balance, and improving gut health, thereby possibly mitigating AD pathogenesis. Moreover, there is paraprobiotics as the most recently developed biotherapeutic with beneficial effects. This review explores the correlation between AD and gut-brain axis as a novel biotherapeutic target. The underlying mechanism of the microbiota-gut-brain axis in AD is examined. Novel insights into the current applications as potential treatment and its limitations are highlighted.