Fish (Alaska Pollock) protein intake attenuates age-related short-term memory decline through gut microbiota modulation

Dysbiosis leads to decreased intestinal barrier function, causing systemic inflammation and possibly the development of age-related cognitive decline. In this study, we investigated the effect of an Alaska pollack protein (APP) diet on cognitive function, gut microbiota composition, intestinal barrier function, and neuroinflammation in senescence-accelerated mouse prone8 (SAMP8) and senescence-resistant AKR/J (SAMR1) mice. The APP diet produced significant improvements across multiple parameters. It enhanced glucose tolerance in both strains and prevented short-term memory decline in SAMP8 mice. Microbiome analysis revealed that APP intake promoted beneficial bacteria growth, specifically increasing Lactobacillus in SAMR1 and butyrate-producing Lachnospiraceae in SAMP8. Notably, while APP diet increased butyrate-producing bacteria in SAMP8, short-chain fatty acids (SCFAs) analysis showed increased aetate but unchanged butyrate levels, suggesting complex metabolic interactions beyond simple bacterial abundance. Moreover, the APP diet significantly suppressed neuroinflammation in SAMP8, evidenced by decreased proinflammatory cytokine expression, microglia and astrocyte activation, and attenuated demyelination in the hippocampus. These findings suggest that APP intake prevents age-related short-term memory decline through beneficial gut microbiota modulation, and reduced neuroinflammation, supporting the role of the gut-brain axis in cognitive aging.