Dietary silver nanoparticle supplementation induces Alzheimer-like lesions through Bifidobacterium deficiency-dominated gut microbiota dysbiosis and neuroinflammation.

Dietary supplement silver nanoparticles have recently drawn attention following reports of hazards associated with long-term use. However, their biosafety, especially their effects on the gut-brain axis, remains largely unexplored. This study demonstrated that dietary supplement silver nanoparticles can accumulate in the intestines, brain, and liver of mice. Chronic exposure to these nanoparticles leads to Alzheimer-like lesions, primarily by disrupting gut microbiota balance. Specifically, this exposure depletes Bifidobacterium and Ruminococcaceae, resulting in reduced intestinal metabolites such as sphingomyelin (d18:1/20:0), tryptophan, and indole. Consequently, this disruption causes neuroinflammation, cognitive impairment, and amyloid-β deposition in mice. Moreover, Bifidobacterium was identified as a key microbial group contributing to Alzheimer-like lesions after exposure, whereas supplementation with Bifidobacterium breve MCC1274 effectively alleviated these lesions. Therefore, the potential risks of silver nanoparticles in dietary supplements should be carefully evaluated. This study provides a promising new direction for the prevention and treatment of Alzheimer-like lesions through microbial interventions.