Fish protein prevents short-term memory decline — Improved gut environment suppresses brain inflammation

While omega-3 fatty acids such as docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) from fish are widely thought to help prevent age-related cognitive decline, fish protein itself may also have the ability to prevent short-term memory loss. This was shown in a study using aged mice by a research team that included Lecturer Yuki Murakami from the Department of Hygiene and Public Health, Faculty of Medicine at Kansai Medical University, and Professor Ryota Hosomi and Professor Kenji Fukunaga from the Faculty of Chemistry, Materials and Bioengineering at Kansai University. Their findings were published in Scientific Reports.

Large-scale cohort studies have shown that dietary patterns centered on Japanese and Mediterranean foods lower the risk of developing dementia. Among people with Japanese dietary habits, those who eat more fish have been found to be less likely to develop dementia. Beneficial effects of omega-3 fatty acids on brain function have also been reported, but it remains unclear whether the positive effects of fish consumption on brain function can be fully explained by DHA and EPA alone.

The research team turned its attention to the protein contained in fish. Prior animal studies have already shown that protein intake is more effective than fatty acid intake in preventing short-term memory decline. However, how fish protein consumption contributes to maintaining brain function was not yet understood.

Meanwhile, recent research has drawn attention to the fact that the gut environment deteriorates with age, leading to a decline in intestinal barrier function, and that systemic inflammation is linked to aging. It has also become clear that inflammation throughout the body can trigger inflammation in the brain, potentially leading to cognitive decline.

The research group fed senescence-accelerated mice prone 8 (SAMP8) and normally aging mice a diet containing Alaska pollock protein (APP) for five months and assessed short-term memory using the Y maze test. To examine the gut environment, they analyzed the gut microbiota from fecal samples. To investigate brain inflammation, they performed histological staining of inflammation-related cells in the hippocampus, which plays a key role in memory.

The Y maze test results showed that SAMP8 mice fed APP maintained better short-term memory than SAMP8 mice fed the control diet. The gut microbiota of SAMP8 mice fed APP also changed: while the control-diet group was dominated by the family Erysipelotrichaceae, which has been reported to promote central nervous system inflammation, the SAMP8 + APP group was dominated by the family Lachnospiraceae, which includes butyrate-producing bacteria. In addition, hepatic gene expression of lipopolysaccharide-binding protein (LBP) was significantly reduced. Immunohistochemical staining of brain tissue further revealed that positive signals for microglia and astrocytes—both of which are activated in response to brain inflammation—were significantly reduced in SAMP8 mice that consumed APP.

These findings confirmed that fish protein intake can prevent short-term memory decline in senescence-accelerated mice, providing scientific evidence for the health benefits of eating fish. The study also shed light on part of the mechanism by which consuming fish—one of the most important protein sources for Japanese people—helps prevent age-related cognitive decline by improving the balance of gut bacteria and strengthening intestinal barrier function.

Journal Information
Publication: Scientific Reports
Title: Fish (Alaska Pollock) protein intake attenuates age-related short-term memory decline through gut microbiota modulation
DOI: 10.1038/s41598-026-38717-y