Dietary emulsifier polysorbate 80 exposure accelerates age-related cognitive decline

Area of Science:

• Neuroscience
• Microbiology
• Gerontology

Background:

• Gut microbial homeostasis is vital for cognitive health in the elderly.
• Polysorbate 80 (P80), a common food emulsifier, alters gut microbiota.
• The impact of long-term P80 exposure on age-related cognitive decline via the gut-brain axis remains unclear.

Purpose of the Study:

• To investigate the effects of P80 on gut microbiota and cognitive function in aging mice.
• To elucidate the mechanisms by which P80 influences the gut-brain axis and cognitive health.

Main Methods:

• Utilized senescence accelerated mouse prone 8 (SAMP8) mice, a model for accelerated aging.
• Administered P80 (1% in drinking water) for 12 weeks.
• Assessed cognitive function, brain pathology, blood-brain barrier integrity, gut microbiota composition, and bile acid metabolism.

Main Results:

• P80 intake exacerbated cognitive decline, increased brain pathological proteins, disrupted the blood-brain barrier, and activated neuroinflammation in SAMP8 mice.
• P80 induced gut dysbiosis, increasing bacteria that produce secondary bile acids like Ruminococcaceae, Lachnospiraceae, and Clostridium scindens.
• Fecal microbiota transplantation from P80-exposed mice worsened cognitive decline and intestinal barrier impairment in recipient mice.
• P80 exposure elevated deoxycholic acid (DCA) levels, which activated microglia and promoted senescence-associated secretory phenotype via ABCA1-mediated cholesterol import.

Conclusions:

• The emulsifier P80 accelerates cognitive decline in aging mice.
• P80 induces cognitive decline through gut dysbiosis, altered bile acid metabolism, disrupted intestinal and blood-brain barriers, and neuroinflammation.
• Dietary P80-induced gut microbiota dysbiosis is a potential risk factor for age-related cognitive decline.