A Cellulose-Rich\nDiet Disrupts Gut Homeostasis and\nLeads to Anxiety through the Gut-Brain Axis

It is widely said that a healthy intestinal environment\nplays an\nessential role in better mental condition. One known dietary nutrient\nthat maintains the intestinal environment is dietary fiber. A recent\nstudy showed that maintaining the intestinal environment with dietary\nfiber alleviated symptoms of psychiatric disorders in animals. However,\nsuch effects have only been reported with soluble fiber, which is\nhighly fermentable and promotes short-chain fatty acid (SCFA) production,\nand not with insoluble fiber. Therefore, we aimed to verify whether\ninsoluble fiber, such as cellulose, can alter emotion via changes\nin the gut. We divided mice into two groups and fed either a standard\ndiet (SD, which contains both insoluble and soluble dietary fibers)\nor a cellulose-rich diet (CRD, which contains cellulose alone as the\ndietary fibers). We found that CRD-fed mice display increased anxiety-like\nbehavior. CRD-fed animals also showed decreased intestinal SCFA levels\nalong with increased intestinal permeability, dysmotility, and hypersensitivity.\nThis behavioral and physiological effect of CRD has been completely\nabolished in vagotomized mice, indicating the direct link between\nintestinal environment exacerbation to the emotion through the gut-brain\naxis. Additionally, we found that amygdalar dopamine signaling has\nbeen modified in CRD-fed animals, and the opioid antagonist abolished\nthis dopaminergic modification as well as CRD-induced anxiety. Altogether,\nour findings indicate that consumption of cellulose alone as the dietary\nfiber may evoke intestinal abnormalities, which fire the vagus nerve,\nthen the opioidergic system, and amygdalar dopamine upregulation,\nresulting in the enhancement of anxiety.