Preventive Nutrition and Food Science · Oct 13, 2026

Gut Microbiota as a Mechanistic Nexus between Type 2 Diabetes and Alzheimer's Disease: Insulin Resistance, Neuroinflammation, and Functional Food Strategies

By Bae YJ, Daily JW, Park S

Type 2 diabetes mellitus (T2DM) and Alzheimer's disease (AD) share substantial pathological overlap, including brain-specific insulin resistance driven by impaired insulin receptor substrate-1/phosphoinositide 3-kinase/protein kinase B signaling, glycogen synthase kinase-3β dysregulation, tau hyperphosphorylation, and amyloid-β accumulation. Brain-insulin resistance is a key mechanistic link between peripheral metabolic dysfunction and neurodegeneration, although the upstream regulatory pathways remain incompletely defined. Gastrointestinal depletion of butyrate-producing microbial taxa and enrichment of pro-inflammatory genera have been independently documented in T2DM and AD. Gut microbiota dysbiosis propagates insulin resistance through at least five pathways: short-chain fatty acid depletion, lipopolysaccharide (LPS)-mediated endotoxemia, bile acid dysregulation, tryptophan-kynurenine imbalance, and vagus nerve disruption. Critically, LPS translocation and kynurenine-driven neurotoxicity propagate AD-relevant neuroinflammation independently of peripheral metabolic dysfunction, implicating a bidirectional gut-brain mechanism. These risks are amplified in Asian populations, who exhibit a lower pancreatic β-cell mass and attenuated insulin secretion that confer disproportionate vulnerability to glucotoxic cycling and its neurological complications. Such a population-specific dimension remains largely absent from reviews. Against this backdrop, traditional Asian fermented foods (chungkookjang, kimchi, and natto) and plant-derived functional ingredients (Eucommia ulmoides, gooseberry, and black garlic) have a preclinical capacity to restore microbial balance, attenuate insulin resistance, and exert neuroprotection. This review integrates these strands into a unified mechanistic and translational framework, positioning gut microbiota modulation through culturally grounded dietary strategies as a tractable approach to reducing the converging burdens of T2DM and AD in Asians.

doi.org/10.3746/pnf.2026.151 Open access PubMed 42935632 Mechanisms