PREBIOTIC SUPPLEMENTATION MITIGATES AGE AND DIET-INDUCED MICROGLIAL DYSFUNCTION IN A SEX-SPECIFIC MANNER

Ageing is associated with increased neuroinflammation, which contributes to declining brain health. Microglia, the resident immune cells of the CNS, play a critical role in regulating neuroinflammation and their dysfunction significantly impacts brain health. The gut microbiota has been shown to significantly influence microglia from birth to adulthood in terms of development, proliferation and function. Diet is a key modulating factor that influences the composition of the gut microbiota, along with prebiotics that support the growth of beneficial gut microbiota. Although the role of diet in neuroinflammation has been well established, its relationship with microglia functionality is less explored. This study investigates the impact of a high-fat diet (HFD) on microglial function in ageing male and female mice, and whether prebiotic supplementation (fructo-oligosaccharides (FOS) and galacto-oligosaccharides (GOS)) can mitigate these effects. Experimental design assessments were conducted to evaluate microglia functionality through phagocytosis, cellular senescence, reactive oxygen species production and inflammatory expressions. Our findings revealed an age-associated decline in microglia functionality in both sexes, with this decline being significantly more prominent in aged males. Female mice demonstrated greater resilience to the long-term detrimental impacts of HFD consumption. Interestingly, in aged male mice, supplementation of the HFD with a prebiotic was sufficient to negate the adverse effects of the diet, indicating beneficial effects of prebiotics (GOS+FOS).