Gut microbiota and inflammation analyses reveal the protective effect of medium-chain triglycerides combined with docosahexaenoic acid on cognitive function in APP/PS1 and SAMP8 mice.

Accumulating evidence has demonstrated that medium-chain triglycerides (MCTs) and docosahexaenoic acid (DHA) positively affect cognitive function. However, it remains unclear whether the improvement is related to the alterations of gut microbiota and inflammation and the impact of the combined intervention. In this study, we hypothesized that the supplementation of MCTs combined with DHA could modulate gut microbiota, inflammation, and improve cognitive function in APPswe/PS1De9 model mice and senescence-accelerated mouse-prone-8, which are two different mouse models used in neurodegeneration research. The mice were divided into four groups: Control group, MCTs group, DHA group, and MCTs + DHA group. The study assessed cognitive function, inflammatory cytokines, and gut microbiota composition. The results showed that supplementation of MCTs + DHA improved spatial learning ability, memory capacity, exploratory behavior; decreased the relative abundance of Proteobacteria; reduced the ratio of Firmicutes/Bacteroidetes; decreased the concentrations of serum interleukin (IL)-2, IL-6, monocyte chemotactic protein-1, tumor necrosis factor-alpha, while increasing the concentration of IL-10. Furthermore, supplementation with MCTs + DHA exhibited significantly superior effects compared to MCTs or DHA alone in reducing inflammation, optimizing gut microbiota composition, and improving cognitive function. In conclusion, supplementation with MCTs + DHA improved cognition function, accompanied with favorable alterations in gut microbiota and inflammation in APPswe/PS1De9 and senescence-accelerated mouse-prone-8 mice.