CELLULOSE RICH FOOD INDUCES INTESTINAL DISTURBANCE THAT LEADS ANXIETY-LIKE BEHAVIOR AND AMYGDALAR DOPAMINERGIC HYPERACTIVITY

Abstract Background It is indicated the intestinal environment affects anxiety and emotions directly in recent years. For example, improvement of intestinal environment is known to suppresses the anxiety-like behavior in mice model of depression and schizophrenia. Such gut-brain relationships, called “gut-brain axis”, are suggested to involve both endocrine and neuronal system via the vagus nerve. However, previous studies have mainly used psychiatric disease models, therefore how intestinal environment will affect on emotion in normal animals remains unclear. Aims & Objectives In the present study, we evaluated the psychological and physiological effect of food-induced intestinal environment modification. Method We divided 7-weeks-old male ICR mice into two groups, and fed either MF (Standard diet: contains various dietary fibers) or AIN-93M (contains cellulose alone) for 8 or 16 weeks. Behavioral test (marble burying test) as well as measurement of peristalsis, cecum short-chain fatty acid (SCFA) and monoamine level of various brain region has been determined in these animals. Results Either 8-weeks or 16-weeks exposure of AIN-93M reduced peristalsis and cecum SCFA, while increased intestinal inflammation, suggesting the exacerbation of intestinal environment in these animals comparing to MF-fed control group. Interestingly, AIN-93M-fed animals also displayed the significant increase of marble-burying behavior compared to MF-fed group, indicating the enhancement of anxiety by that 16-week exposure to AIN-93M. These effects were abolished by vagotomy, suggesting that enhanced anxiety is caused by the AIN-93M-induced intestinal disturbance through gut-brain axis. We also found the dopamine level in amygdala was significantly increased in the AIN-93M-fed group. Discussion & Conclusion These results suggest that the cellulose-induced intestinal disturbance and decreased intestinal function caused overactivation of dopaminergic system, which may enhance the anxiety level. Also as vagus nerve is critical to the anxiety observed in cellulose-fed animals, we propose that exacerbation of gut environment may directly cause the mental illness or psychiatric disorder through gut-brain axis.