HUA Yi-nan, SU Jun, ZHOU Mo-long, HU Jing, YAO Xin-yue, MA Wei-wei
Acta Nutrimenta Sinica. 2026, 48(1): 54-63.
Objective To investigate the effects of high-fat diets containing different types of fatty acids on cognitive function in mice via gut microbiota. Methods 3-week-old male C57BL/6J mice were randomly assigned into 9 groups. Except for the control-0 (CON-0) group, all mice underwent 4-week aseptic treatment. Thereafter, the CON-0 and CON-1 groups were intragastrically administered normal saline, while the remaining groups received fecal microbiota from donor mice fed different experimental diets for 10 consecutive weeks. The fecal microbiota transplantation groups included +CON group, +long-chain saturated fatty acid (+LCSFA) (lard-enriched) group, +medium-chain saturated fatty acid (+MCSFA) (coconut oil-enriched) group, +n-3 polyunsaturated fatty acid (+n-3 PUFA) (linseed oil-enriched) group, +n-6 PUFA group, and +trans fatty acid-enriched (+TFA) soybean oil-enriched group. The learning and memory ability of 21-week-old mice was evaluated by Morris water maze test. Mice aged 23-week were anesthetized and blood samples, distal colon, brain tissue, and visceral fat were collected. Lipopolysaccharide (LPS), D-lactate (D-LA), diamine oxidase (DAO), and intestinal fatty acid binding protein (I-FABP) were detected by ELISA. HE staining was used for colon tissues. The expression of IL-1β and TGF-β1 in colon tissues was detected by immunohistochemistry. Additionally, fully automated Western blotting was employed to detect the expressions of inflammatory factors including toll-like receptor-4 (TLR-4), myeloid differentiation factor 88 (MyD88), and nuclear factor-κB (NF-κB) p65 in brain tissues. Results The adiposity index (AI) of the +MUFA and +TFA groups were higher than that of the CON-0、CON-1 and +LCSFA groups. Compared with the +MCSFA, +n-3 PUFA, and +MUFA groups, escape latency was significantly prolonged in the +LCSFA group on the fourth day of water maze test. Plasma levels of DAO, I-FABP and LPS were elevated in the +LCSFA, +MCSFA, +MUFA and +TFA groups. In the +LCSFA, +MCSFA, +MUFA and +n-6 PUFA groups, colonic crypt structures were altered to varying degrees, accompanied by a reduction in goblet cells, inflammatory cells, as well as epithelial cell necrosis and shedding. In the colon, IL-1β was significantly elevated in the +MCSFA and +n-6 PUFA groups, while it was significantly reduced in the +n-3 PUFA and +TFA groups. TGF-β1 was significantly elevated in the +n-3 PUFA group, while it was significantly reduced in the +LCSFA and +MCSFA groups. In the brain, TLR-4 and p65 expressions were elevated in the +MCSFA, +n-6 PUFA and +MUFA groups, and the p65 expression was elevated in the +TFA group. All of these differences were statistically significant (P<0.05). Conclusion Gut microbiota modulated by high-fat diets enriched in LCSFA, MCSFA, MUFA, n-6 PUFA and TFA might increase the intestinal barrier permeability, which in turn promotes inflammatory states in the brain, leading to altered cognitive function in mice. Conversely, n-3 PUFAs may exert inhibitory effects on these processes.
