Sex hormones and diets rich in polyunsaturated ω-6/ω-3 fatty acids modify microbiota distinctly in a mouse model of Alzheimer’s disease

There is considerable data suggesting that the gut microbiota (GM) contributes to health and regulates host immunity and influences brain function, findings with implications for neurodegenerative diseases, such as Alzheimer's Disease (AD). In the present study, using three non-fat diets with different ratios of unsaturated ω-6/ω-3 fatty acids (FAs)(high or low), we analyzed how minor differences in diet can affect the microbiota of amyloid precursor protein/Presenilin 1 transgenic (APP/PS1 [TG]) mice, a mice model of AD, next, we studied how the levels of sex hormones may affect the GM. The data obtained show that sex hormones in males fed our standard diet (S) modified alpha and beta diversity, whereas no differences were observed in TG mice compared with wild-type mice. Moreover, there were significant differences in both alpha or beta diversity in mice fed with an H or L diet compared with an S diet. In conclusion, our data indicate that the levels of sex hormones or differences in the ω-6/ω-3 FA ratio alter the GM more than expected. Thus, it is tantalizing to propose that low levels of ω-3 FAs in APP/PS1 mice fed an "H" diet may be responsible for modifying some bacterial genera, exacerbating the basal neuropathology in this AD model.