In C57BL/6 mice, long-term feeding of a diet high in fats and carbohydrates is linked to changes in gut microbes, increased leakage in the intestinal barrier, inflammation throughout the body and...
Mechanism
Synthesis from 1 study
Too much fat and sugar changes gut bacteria, which damages the gut lining and lets toxins into the blood. These toxins hurt the energy parts of cells, causing them to leak DNA. The body mistakes this DNA for an infection and turns on inflammation. That inflammation spreads to the brain, kills...
Most probable mechanism
Eating too much fat and sugar for a long time changes the good bacteria in the gut, causing the gut lining to become leaky. This lets harmful bacterial parts escape into the bloodstream, which damages the energy factories inside cells. When these energy factories break down, they release their own DNA into the cell fluid, which tricks the body into thinking there's an infection. This turns on alarm systems that release powerful inflammatory signals, some of which reach the brain and activate its immune cells. Over time, this constant inflammation kills brain cells involved in memory and learning, leading to trouble with thinking and remembering.
Chronic consumption of a high-fat, high-carbohydrate diet alters the composition of gut microbiota, reducing beneficial species and increasing pro-inflammatory microbial strains
Dysbiosis compromises intestinal epithelial integrity, increasing permeability and enabling translocation of microbial products such as lipopolysaccharide into systemic circulation
Systemic exposure to microbial products induces mitochondrial dysfunction in peripheral and central cells, suppressing expression of mitochondrial transcription factor A
Mitochondrial damage causes release of mitochondrial DNA into the cytosol, where it acts as a damage-associated molecular pattern
Cytosolic mitochondrial DNA activates the AIM2 inflammasome and cGAS-STING pathways, triggering caspase-1-mediated maturation of interleukin-1β and interleukin-18, and IRF3-dependent production of type I interferons
Pro-inflammatory cytokines and interferons cross the blood-brain barrier or activate resident microglia and astrocytes, initiating neuroinflammation
Chronic neuroinflammation activates intrinsic apoptotic pathways in hippocampal neurons, leading to neuronal loss and synaptic dysfunction
Hippocampal neuronal loss and impaired synaptic plasticity reduce the capacity for learning and memory formation, resulting in measurable cognitive deficits
Evidence from Studies
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