A possible link between food and mood: dietary impact on gut microbiota and behavior in BALB/c mice

Abstract

Major depressive disorder is a debilitating disease in the Western World. A western diet high in saturated fat and refined sugar seems to play an important part in disease development. Therefore, this study is aimed at investigating whether saturated fat or sucrose predisposes mice to develop behavioral symptoms which can be interpreted as depression-like, and the possible influence of the gut microbiota (GM) in this. Fourty-two mice were randomly assigned to one of three experimental diets, a high-fat, a high-sucrose or a control diet for thirteen weeks. Mice on high-fat diet gained more weight (p = 0.00009), displayed significantly less burrowing behavior than the control mice (p = 0.034), and showed decreased memory in the Morris water maze test compared to mice on high-sucrose diet (p = 0.031). Mice on high-sucrose diet burrowed less goal-oriented, showed greater latency to first bout of immobility in the forced swim test when compared to control mice (p = 0.039) and high-fat fed mice (p = 0.013), and displayed less anxiety than mice on high-fat diet in the triple test (p = 0.009). Behavioral changes were accompanied by a significant change in GM composition of mice fed a high-fat diet, while no difference between diet groups was observed for sucrose preferences, LPS, cholesterol, HbA1c, BDNF and the cytokines IL-1α, IL-1β, IL-6, IL-10, IL-12(p70), IL-17 and TNF-α. A series of correlations was found between GM, behavior, BDNF and inflammatory mediators. In conclusion, the study shows that dietary fat and sucrose affect behavior, sometimes in opposite directions, and suggests a possible association between GM and behavior.

Figure 1. Timeline illustrating the experimental period.

Numbers indicate week number, with mice subjected to the experimental diets from time 0. HbA1c: Glycosylated hemoglobin 1c, WM: Water Maze.

Figure 2. The Burrowing test.

Mice on HF diet removed significantly less bedding material from the tube than mice on C diet (p = 0.035). A tendency of reduced burrow-digging is seen for mice on HS diet (p = 0.064). However, although not quantified, this diet group burrowed less goal-oriented, as observations showed excessive digging in the whole cage. Median with ranges.

Figure 3. The Triple test, time spent in the aversive centre of the open field at post-diet test.

Mice on high-sucrose diet spent significantly more time here than the mice on high-fat diet, indicating a decreased anxiety (p = 0.009). A strong tendency of a similar difference to mice on control diet supports this decreased anxiety in mice fed a high-sucrose diet (p = 0.052). Mean with SE.

Figure 4. The Morris water maze test, distance swum and latency to reach the platform.

A general day to day significant decrease in distance swum and latency to reach platform was seen for all diet groups, indicating that all diet groups learned the task. However, a high-fat diet seemed to influence negatively on coping with the start position sequence on day three. Median with ranges.

Figure 5. The Morris water maze test, preference for the previous platform area.

Mice on high-fat diet spent significant less time in the area of the previous situated platform during the first 30 seconds of the retention trial compared to mice on high-sucrose diet. Memory of mice on control diet was similar to mice on high-sucrose diet. This indicate, that consuming a high-fat diet leads to decreased memory. Mean with SE.

Figure 6. 3D plots of the unweighted and weighted PCoA of cecum.

Plots are constructed from the three most primary principal components of the PCoA, with A) showing the unweighted analysis and B) showing the weighted analysis which takes the abundance of the bacteria into account. Both plots visualize that the cecal GM of mice fed a high-fat diet diverge from that of mice fed either a high-sucrose or a control diet.