A Cellulose-Rich Diet Disrupts Gut Homeostasis and Leads to Anxiety through the Gut-Brain Axis

• Published in: ACS pharmacology & translational science 2024-10, Vol.7 (10), p.3071-3085
• Main Authors: Ito, Kaede, Hosoki, Haruka, Kasai, Yuya, Sasaki, Hiroyuki, Haraguchi, Atsushi, Shibata, Shigenobu, Nozaki, Chihiro
• Format: Article
• Language: English
• ISSN: 2575-9108; 2575-9108
• DOI: 10.1021/acsptsci.4c00270

It is widely said that a healthy intestinal environment plays an essential role in better mental condition. One known dietary nutrient that maintains the intestinal environment is dietary fiber. A recent study showed that maintaining the intestinal environment with dietary fiber alleviated symptoms of psychiatric disorders in animals. However, such effects have only been reported with soluble fiber, which is highly fermentable and promotes short-chain fatty acid (SCFA) production, and not with insoluble fiber. Therefore, we aimed to verify whether insoluble fiber, such as cellulose, can alter emotion via changes in the gut. We divided mice into two groups and fed either a standard diet (SD, which contains both insoluble and soluble dietary fibers) or a cellulose-rich diet (CRD, which contains cellulose alone as the dietary fibers). We found that CRD-fed mice display increased anxiety-like behavior. CRD-fed animals also showed decreased intestinal SCFA levels along with increased intestinal permeability, dysmotility, and hypersensitivity. This behavioral and physiological effect of CRD has been completely abolished in vagotomized mice, indicating the direct link between intestinal environment exacerbation to the emotion through the gut-brain axis. Additionally, we found that amygdalar dopamine signaling has been modified in CRD-fed animals, and the opioid antagonist abolished this dopaminergic modification as well as CRD-induced anxiety. Altogether, our findings indicate that consumption of cellulose alone as the dietary fiber may evoke intestinal abnormalities, which fire the vagus nerve, then the opioidergic system, and amygdalar dopamine upregulation, resulting in the enhancement of anxiety.