Microbiome-targeted Alzheimer's interventions via gut-brain axis

Area of Science:

• Neuroscience
• Microbiology
• Gastroenterology

Background:

• Alzheimer's disease (AD) is a progressive neurodegenerative disorder with limited therapeutic options.
• The gut-brain axis plays a crucial role in AD pathogenesis, with gut dysbiosis identified as a significant contributing factor.
• Gut dysbiosis involves an imbalance of gut microbiota, leading to compromised intestinal and blood-brain barrier integrity and systemic inflammation.

Purpose of the Study:

• To review the role of the gut-brain axis and gut dysbiosis in Alzheimer's disease.
• To evaluate promising interventions targeting the gut microbiome for AD treatment.
• To identify challenges and future research directions for clinical translation.

Main Methods:

• Literature review of preclinical and clinical studies on the gut-brain axis in AD.
• Analysis of the impact of gut dysbiosis on neuroinflammation, amyloid-beta deposition, and tau pathology.
• Evaluation of interventions such as probiotics, diet, exercise, and phytochemicals.

Main Results:

• Gut dysbiosis disrupts microbial metabolites, reducing neuroprotective SCFAs and indoles while increasing inflammatory mediators.
• This imbalance exacerbates neuroinflammation, amyloid-beta deposition, and tau pathology, contributing to AD progression.
• Interventions like probiotics and anti-inflammatory diets show potential in preclinical and early clinical studies to restore microbial balance and improve outcomes.

Conclusions:

• The gut-brain axis represents a promising therapeutic target for Alzheimer's disease.
• Clinical translation of gut-targeted interventions is limited by reliance on animal models and insufficient mechanistic understanding.
• Future research should focus on large-scale human trials, multi-omics analysis, and personalized approaches to leverage the gut-brain axis for AD treatment.