Dietary lipids are essential for brain health. However, high-fat diets (HFD) have produced conflicting results in studies on aging brain health, likely due to variations in fatty acid composition. While aging-related glial lipid accumulation is exacerbated by saturated fatty acids (SFAs)-rich HFD, it remains unclear whether replacing SFAs with n-3 polyunsaturated fatty acids (PUFAs) can mitigate this effect and the associated neuroinflammation. This study investigates the effects of SFAs-rich and n-3 PUFAs-rich HFDs in 18-month-old C57BL/6J mice over a 12-week period. Mice fed the SFAs-rich HFD showed increased body weight, elevated glucose and lipid levels, and lipid accumulation in glial cells. Behavioral tests, including novel object recognition and the Barnes maze, revealed significant cognitive impairments in these mice. In contrast, the n-3 PUFAs-rich HFD increased brain docosahexaenoic acid levels, activated the ATP-binding cassette transporter A1/apolipoprotein E pathway, reduced lipid accumulation in glial cells, and ultimately reversed cognitive decline. Consistent with these findings, the n-3 PUFAs-rich diet also attenuated inflammatory markers such as tumor necrosis factor α and interleukin 1β, and decreased oxidative stress markers including malondialdehyde and oxidized glutathione/reduced glutathione. These findings provide novel insights into the role of fatty acid composition in HFD affecting aged brain health, offering strong evidence for the neuroprotective benefits of n-3 PUFAs-enriched diets.

Diabetic retinopathy (DR) is a significant cause of vision impairment in adults with diabetes, however, effective treatments remain limited. This study investigated the effects of synbiotic supplementation combining Parabacteroides distasonis (P. distasonis) and highland barley-derived β-glucan on retinopathy in a db/db mouse model of type 2 diabetes. In our experimental approach, male db/db mice were orally administered P. distasonis (2 × 10^8 CFU/mL), barley β-glucan (1% dietary supplementation), the combination of both, or PBS daily for 8 weeks. We assessed retinal morphology and vascular integrity through histological analysis, and examined gut microbiota composition via 16S rRNA gene sequencing. Serum bile acid profiles were analyzed using liquid chromatography-mass spectrometry, and gene expression in tissues was quantified by qRT-PCR. We observed that synbiotic treatment improved retinal thickness and attenuated vascular damage compared to untreated diabetic controls. The synbiotic intervention enhanced gut barrier integrity and altered gut microbiota composition. Furthermore, synbiotic supplementation altered serum bile acid profiles, elevating levels of ursodeoxycholic acid (UDCA) and tauroursodeoxycholic acid (TUDCA), which may play protective roles in retinal cells. Mechanistically, these changes were associated with activation of bile acid signaling pathways in the liver and gut, and reduced expression of inflammatory markers in the retina. Our findings suggest that targeted synbiotic intervention may offer a novel therapeutic approach for preventing or treating diabetic retinopathy through modulation of the gut-retina axis and bile acid metabolism.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder influenced by genes and the environment. This study investigated the protective effects of bovine milk fat globule membrane (BMFGM) and goat milk fat globule membrane (GMFGM) supplementation on ASD model mice. Analysis of phospholipid composition showed higher levels of phosphatidylcholine in BMFGM and phosphatidylethanolamine in GMFGM. Behavioral results indicated MFGMs ameliorated social deficits, with GMFGM being more effective. Milk fat globule membrane (MFGM) mitigated neuroinflammation by suppressing microglial overactivation and proinflammatory cytokines expression, meanwhile GMFGM increased the anti-inflammatory factor interleukin (IL)-10. MFGMs also altered gut microbiota composition and maintained gut barrier integrity. Uniquely, GMFGM increased butyrate production. Correlation analysis revealed positive associations between social behavior, levels of phosphatidylcholine, sphingomyelin, and the abundance of Allobaculum, Clostridium_sensu_stricto, and Turicibacter. Overall, these findings revealed the protective effects of MFGMs on neurodevelopment in ASD animal models and the underlying mechanism could be partly explained by their regulation of gut microbiota by the phospholipid components in MFGM.