Microbiome Engineering for Biotherapeutic in Alzheimer's Disease Through the Gut-Brain Axis: Potentials and Limitations.

2025-06-02
International journal of molecular sciences 26(11)

PubMed: 40508160
DOI: 10.3390/ijms26115351

Study Design

Type: Review
Methods: 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.

Rigorous Journal

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.

Research Insights

Supplement	Dose	Health Outcome	Effect Type	Effect Size	Source
Bifidobacterium bifidum HA-132	—	Improved Gut Health	Beneficial	Small	View source 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
Bifidobacterium bifidum HA-132	—	Normalized Neurotransmitter Levels	Beneficial	Small	View source probiotic, prebiotic, synbiotic, and postbiotics can positively modulate the gut-brain axis, reducing systemic inflammation, restoring neurotransmitter balance, and improving gut health
Bifidobacterium bifidum HA-132	—	Reduced Inflammation	Beneficial	Small	View source probiotic, prebiotic, synbiotic, and postbiotics can positively modulate the gut-brain axis, reducing systemic inflammation, restoring neurotransmitter balance, and improving gut health
Bifidobacterium breve HA-129	—	Improved Cognitive Function	Beneficial	Small	View source The review highlights 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.