The probiotic Lactobacillus kefiranofaciens K6 alleviates exercise and sleep deprivation-induced physiological dysregulation and neuropsychiatric disorders via modulation of inflammation, circadian rhythm, and stress response.

Individuals often suffer from insufficient or disrupted sleep due to night shifts, work pressure, and irregular lifestyles. Sleep deprivation (SD), defined as an intentional or unintentional reduction in sleep quality or quantity, has been associated with an increased risk of metabolic disorders, gut dysbiosis, emotional disturbances, and diminished performance in occupational and physical activities. Functional probiotics have been shown to regulate physiological homeostasis and ameliorate diseases through their impact on the microbiota and various physiological pathways. In this study, we employed the modified multiple platform method (MMPM) to induce SD in an animal model, simulating physiological dysregulation and psychological characteristics associated with SD. We further investigated whether exercise and the probiotic Lactobacillus kefiranofaciens K6 could mitigate the effects of SD on physiological homeostasis, neuropsychological function, inflammation, circadian rhythm, and exercise capacity. We found that the probiotic K6 significantly alleviated depression and anxiety while improving glucose intolerance and declining endurance capacity in the SD model. Elevated injury indexes (CK and LDH) induced by SD combined with exercise training were also significantly reduced under K6 supplementation. In the liver and muscle, SD alone or combined with exercise led to inflammation (TNF-α) and dysregulated circadian gene expression (BMAL-1, CLOCK), both of which were mitigated by K6 supplementation. In the intestine, hypothalamus, and hippocampus, SD or SD combined with exercise-induced inflammation (TNF-α, IL-1β) and tight junction hyperpermeability (Claudin-1, ZO-1) were alleviated with K6 supplementation, as were the circadian genes (BMAL-1, CLOCK) and corticotropin-releasing hormone receptor genes (CRF1, CRF2) in hypothalamus and hippocampus under SD alone or combined with exercise. The functional probiotic K6 improved physiological adaption, neuropsychological behaviors, and exercise performance with the implementation of SD and exercise training, potentially through regulation of inflammation, circadian rhythm, and stress response, contributing to overall health maintenance. The K6 probiotic strain may serve as a nutritional strategy to mitigate health risks and enhance performance affected by sleep deprivation.