Dietary emulsifier polysorbate 80 exposure accelerates age-related cognitive decline

Apr 2, 2024Brain, behavior, and immunity

Daily intake of emulsifier polysorbate 80 may speed up memory decline with age

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Abstract

Long-term intake of 1% polysorbate 80 (P80) in drinking water for 12 weeks exacerbated cognitive decline in aging mice.

P80 intake resulted in increased deposition of brain pathological proteins and disruption of the blood-brain barrier.
Activation of microglia and neurotoxic astrocytes was observed following P80 exposure.
Gut microbiota dysbiosis was induced by P80, with notable increases in bacteria associated with secondary bile acid production.
Fecal microbiota transplantation from P80-treated mice into other mice aggravated cognitive decline and intestinal barrier impairment.
Altered gut microbial composition led to significant changes in bile acid metabolism, including elevated deoxycholic acid levels in serum and brain tissue.
Deoxycholic acid may promote neuroinflammation by activating microglia and influencing cholesterol metabolism.

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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 metabolism alteration, intestinal barrier and blood brain barrier disruption as well as neuroinflammation. This study provides strong evidence that dietary-induced gut microbiota dysbiosis may be a risk factor for age-related cognitive decline.

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Dietary emulsifier polysorbate 80 exposure accelerates age-related cognitive decline

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