Altered intestinal microbiota induced by high-fat diets affect cognition differently in mice

Abstract

The role of the gut microbiota in the association between high-fat diet and cognition is not clear. We hypothesized that a high-fat diet may influence cognition by altering the intestinal microbiota. Fecal microbiota isolated from male C57BL/6J mice feeding on various high-fat diets and a control basic diet were transplanted to antibiotic-treated recipient mice. The measurement of weight and plasma lipids, novel object recognition test, 16S rRNA gene sequencing of feces, and hematoxylin-eosin staining of the hippocampal cornu ammonis 1 and cornu ammonis 3 areas were performed for all mice. Compared with those in the control and n-3 polyunsaturated fatty acid (n-3 PUFA) groups, donor obese mice fed with diets high in long-chain saturated fatty acids, n-6 polyunsaturated fatty acids (n-6 PUFAs), and trans fatty acids exhibited significant cognitive impairment (all P < .05). There were fewer neurons in the hippocampal area in the n-6 PUFA group than in the n-3 PUFA group (P < .05). Similar effect on cognition and neurons in hippocampal area in corresponding recipient mice were revealed after fecal microbiota transplantation. In addition, the composition of intestinal microbiota differed among recipient mice after fecal microbiota transplantation from donor mice. According to these results, it was concluded that diets rich in long-chain saturated fatty acids, n-6 PUFAs, and trans fatty acids may lead to cognitive impairment by damaging the structure of the hippocampus through influencing the intestinal microbiota in mice, whereas a diet high in n-3 PUFAs may exhibit a beneficial effect.