Dietary emulsifier polysorbate 80 exposure accelerates age-related cognitive decline

[Display omitted] •Emulsifier Polysorbate 80 exposure significantly exacerbated age-related cognitive decline, along with increased brain pathological proteins deposition and neuroinflammation, as well as disruption of the blood–brain barrier.•Emulsifier Polysorbate 80 exposure contributed to gut microbiota dysbiosis and the increased of deoxycholic acid in plasma and brain.•Emulsifier Polysorbate 80 induced cognitive decline and neuroinflammation via gut microbiota.•Mechanically, deoxycholic acid activates microglial cells may involve the upregulation of ABCA1-mediated cholesterol transport on lysosomes, thereby promotes the senescence-associated secretory phenotype. Gut microbial homeostasis is crucial for the health of cognition in elderly. Previous study revealed that polysorbate 80 (P80) as a widely used emulsifier in food industries and pharmaceutical formulations could directly alter the human gut microbiota compositions. However, whether long-term exposure to P80 could accelerate age-related cognitive decline via gut-brain axis is still unknown. Accordingly, in this study, we used the senescence accelerated mouse prone 8 (SAMP8) mouse model to investigate the effects of the emulsifier P80 intake (1 % P80 in drinking water for 12 weeks) on gut microbiota and cognitive function. Our results indicated that P80 intake significantly exacerbated cognitive decline in SAMP8 mice, along with increased brain pathological proteins deposition, disruption of the blood–brain barrier and activation of microglia and neurotoxic astrocytes. Besides, P80 intake could also induce gut microbiota dysbiosis, especially the increased abundance of secondary bile acids producing bacteria, such as Ruminococcaceae, Lachnospiraceae, and Clostridium scindens. Moreover, fecal microbiota transplantation from P80 mice into 16-week-old SAMP8 mice could also exacerbated cognitive decline, microglia activation and intestinal barrier impairment. Intriguingly, the alterations of gut microbial composition significantly affected bile acid metabolism profiles after P80 exposure, with markedly elevated levels of deoxycholic acid (DCA) in serum and brain tissue. Mechanically, DCA could activate microglial and promote senescence-associated secretory phenotype production through adenosine triphosphate-binding cassette transporter A1 (ABCA1) importing lysosomal cholesterol. Altogether, the emulsifier P80 accelerated cognitive decline of aging mice by inducing gut dysbiosis, bile acid metabolis