Microbiome Alterations and Alzheimer's Disease: Modeling Strategies with Transgenic Mice

Area of Science:

• Microbiology
• Neuroscience
• Gastroenterology

Background:

• The microbiota-gut-brain axis is increasingly linked to neurodegenerative (Alzheimer's disease, AD) and metabolic (diabetes) disorders.
• A balanced gut microbiota supports intestinal barrier integrity, immune modulation, and produces neurotransmitters and short-chain fatty acids.
• Gut dysbiosis can lead to immune dysregulation, neuroinflammation, and compromised blood-brain barrier, potentially exacerbating AD pathology.

Purpose of the Study:

• To review the role of germ-free and transgenic animal models in understanding the link between gut dysbiosis, metabolic diseases, and Alzheimer's disease.
• To explore novel therapeutic targets for AD by examining the microbiota-gut-brain axis.
• To highlight the impact of lifestyle and diet on the gut microbiome and AD risk factors.

Main Methods:

• Utilizing germ-free animal models to study microbial-free environments.
• Employing transgenic animal models to investigate specific genetic and microbial interactions.
• Reviewing existing literature on the microbiota-gut-brain axis in AD and metabolic disorders.

Main Results:

• Dysbiosis contributes to neuroinflammation and AD progression via immune dysregulation and microbial products crossing the blood-brain barrier.
• Animal models are crucial tools for dissecting the complex interactions within the microbiota-gut-brain axis.
• Dietary habits significantly influence both the gut microbiota and established AD risk factors like diabetes and obesity.

Conclusions:

• Alzheimer's disease should be viewed as a systemic disorder influenced by the gut microbiome.
• Microbiome-based therapies and lifestyle modifications represent promising complementary strategies for AD management.
• Further research using animal models is essential to identify and validate new therapeutic avenues targeting the microbiota-gut-brain axis.