Masticatory Training Mitigates Stress-Induced Physical Response and Modulates Cecal Metabolic Profiles in Powder-Diet-Fed Mice

Oral hypofunction is an early indicator of systemic frailty. Although reduced masticatory stimuli impair physical and mental functions, their impact on the gut metabolic environment and systemic stress resilience remains poorly understood. We investigated whether 28-d masticatory training could modulate cecal metabolic profiles and mitigate restraint stress-induced weight loss. Mice were fed hard or soft diets for 17 weeks to induce masticatory deficiency, with training groups undergoing 2 h of daily masticatory exercise during the final 4 weeks. In Experiment 1, we analyzed cecal organic acids under the basal metabolic state; 28-d preconditioning did not significantly alter levels in trained soft-diet-fed mice. In Experiment 2, we subjected mice to a 2-h acute stress challenge to evaluate resilience. We observed that while the challenge significantly changed the levels of eight cecal organic acids, acetate, butyrate, and 4-methylvalerate levels were significantly lower in the trained soft-diet-fed group than in the non-trained group, reflecting a normalized metabolic and gastrointestinal environment. In Experiment 3, the trained soft-diet-fed mice exhibited high stress resilience, which was characterized by maintaining body weight and fecal water content (%), and increasing fecal pellet counts. These findings suggest that masticatory training in soft-diet-fed mice mitigates stress-induced weight loss and physiological disturbances, along with modulating gastrointestinal function and cecal metabolic responses. These findings suggest the potential of masticatory training as a noninvasive strategy to help mitigate the systemic consequences of oral hypofunction, providing a foundation for future clinical and translational research.