Dietary Fiber Deprivation Disrupts Colonic Homeostasis to Drive Anxiety-Like Behavior via the Gut-Brain Axis

Low-fiber diet poses a health risk, yet mechanisms linking dietary fiber deprivation to emotional disorders are unclear. Here, we demonstrate that dietary fiber deprivation (FD) induces pronounced anxiety-like behaviors in mice by disrupting the gut-brain axis. In the FD model, a 6-week intervention with mannan oligosaccharides (MOS, 500 mg/kg) ameliorated these deficits. Mechanistically, FD disrupted gut microbiota and impaired gut barrier integrity. FD triggered colonic inflammation, oxidative stress, and inhibited mitochondrial oxidative phosphorylation─a critical aspect of colonic energy metabolism. These intestinal insults were associated with hyperactivation of the HPA axis and neuroinflammation in the brain. MOS reversed these effects by reshaping the gut microbiota, promoting short-chain fatty acids (SCFAs), and restoring colonic energy homeostasis. Colonic energy metabolism is a critical node in the gut-brain axis, linking fiber intake to emotional regulation. Therefore, dietary fiber deprivation affects the HPA axis and emotions, making it an important nutritional intervention target.