Alterations and mechanistic insights of gut microbiota and its metabolites in type 2 diabetes mellitus and Alzheimer's disease.
- 2025-05-11
- iMetaOmics 2(3)
- PubMed: 41674561
- DOI: 10.1002/imo2.70020
Study Design
- Type
- Review
- Methods
- This narrative review provides an in-depth examination of the roles and mechanisms of gut microbiota and their metabolites in the context of T2DM and AD.
Epidemiological studies suggest a link between type 2 diabetes mellitus (T2DM) and Alzheimer's disease (AD), possibly due to gut microbiota dysbiosis, although the exact mechanisms are unclear. This narrative review uniquely addresses how gut microbiota-derived metabolites mediate overlapping pathologies of insulin resistance, neuroinflammation, and amyloidogenesis in T2DM and AD, proposing a framework for dual therapeutic targeting. This narrative review provides an in-depth examination of the roles and mechanisms of gut microbiota and their metabolites in the context of T2DM and AD. This study indicates that gut microbiota dysbiosis significantly impacts the pathogenesis and progression of both diseases by modulating metabolic pathways, immune functions, and inflammatory responses. Key bacteria, such as Akkermansia muciniphila (which releases outer membrane vesicles), Lactobacillus, and Bifidobacterium, as well as their metabolites like short-chain fatty acids (SCFAs), bile acids (BAs), lipopolysaccharide (LPS), vitamins, and Trimethylamine N-oxide (TMAO) regulate T2DM and AD through complex mechanisms. Multiple signaling pathways, including G-protein coupled receptor 41/43 (GPR41/43), phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt), Toll-like receptor 4 (TLR4)/nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), and endoplasmic reticulum (ER) stress-mediated pathways, are also involved. These findings offer insights into the pathogenesis and potential targeted therapies for T2DM and AD.
Research Insights
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