Chronic Exposure to Thermally Processed Food-Derived Carbon Polymers Accelerated Neuroinflammation in Alzheimer Disease Mice through Microbe-Gut-Brain Axis.

Processed foods are increasingly associated with the prevalence of neurodegenerative diseases, including Alzheimer disease (AD). Therefore, it is essential to elucidate the underlying mechanisms by which these processed foods influence AD. This study identified and isolated an emerging dietary risk factor, carbon-based polymers (CPs), from processed foods, specifically roasted lamb. Further investigation revealed that prolonged exposure to CPs induced gut microbiota dysbiosis along with elevated endotoxin production and perturbed tryptophan metabolism, thereby leading to intestinal inflammation. These alterations facilitated the entry of LPS into the blood circulation, which subsequently triggered systemic inflammation and increased the blood-brain barrier permeability. Ultimately, they accelerated neuroinflammation and synaptic dysfunction in transgenic APPswe/PSEN 1dE9 mice via the LPS-TLR4-NF-κB signaling pathway. Collectively, this study advances our understanding of CPs as potential accelerators of neuroinflammation, providing a scientific basis for reevaluating the biosafety of dietary CPs in humans, especially for at-risk populations.