講師資料
Talks:
Gut-Brain Axis Modulation in Sleep Disturbance: Effects of Probiotic Intervention in Animal Models of Chronic Insomnia and Alzheimer's Disease
腸腦軸調控與睡眠障礙:益生菌介入對慢性失眠及阿茲海默症動物模式之影響
Name:
陳玠文(Chieh-Wen Chen)
Position:
Assistant Professor; Assistant Research Fellow
Affiliation:
Institute of Neuroscience; Research Center for Mind, Brain, and Learning; National Chengchi University, Taipei, Taiwan
Email:
Photo:
Research Interests:
Sleep physiology; autonomic regulation; biomedical signal analysis; cognitive neuroscience; gut–brain axis; neurodegenerative diseases
Selected Publications:
1. Chen, C. W., Kuo, T. B. J., Hsu, P. C., Li, J. Y., Kuo, K. L., Yang, C. C. H. Roles of sleep-related cardiovascular autonomic functions in voluntary exercise-induced alleviation of hypertension in spontaneously hypertensive rats. Hypertension Research 202204, 45.7: 1154-1167.
2. Chen, C. W., Kwok, Y. T., Cheng, Y. T., Huang, Y. S., Kuo, T. B. J., Wu, C. H., Du, P. J., Yang, A. C., Yang, C. C. H. Reduced slow-wave activity and autonomic dysfunction during sleep precede cognitive deficits in Alzheimer's disease transgenic mice. Scientific Reports 202307, 13: 11231.
3. Chen, C. W., Chen, H. C., She, S. C., Lai, C. T., Chen, W. J., Kuo, T. B. J., Yang, C. C. H. Levilactobacillus brevis SG031 modulates mood-related behaviors and attenuates stress-related sleep disturbance and autonomic dysfunction via gut microbiota modulation in Wistar–Kyoto rats. Life Sciences 202406, 122804.
Abstract:
Background: Sleep disturbance is closely linked to autonomic dysfunction, neuroinflammation, affective symptoms, and cognitive decline. Growing evidence also implicates the gut-brain axis in both chronic insomnia and Alzheimer's disease (AD), but the microbial changes accompanying probiotic-related improvements in sleep and brain function remain incompletely understood. We therefore evaluated probiotic interventions in two distinct animal models: rats with caffeine-induced chronic insomnia and APP/PS1 transgenic mice.
Methods: In the chronic insomnia study, sustained caffeine release through subcutaneous osmotic pumps was used to disrupt sleep in rats for four weeks. Animals received either a live probiotic preparation or its heat-treated postbiotic preparation for six weeks, beginning two weeks before caffeine exposure. Wireless electroencephalogram, electromyogram, and electrocardiogram recordings were combined with behavioral testing and analyses of inflammatory markers and neural activity in sleep-promoting and wake-promoting brain regions. Fecal microbiota were characterized using 16S rRNA sequencing. In the AD study, APP/PS1 mice received a probiotic formulation combining two strains for eleven weeks, beginning at 20 weeks of age, an early stage in the disease course. Sleep and autonomic function, anxiety-like behavior, learning and memory, amyloid-beta deposition, neuroinflammation, and fecal microbiota were assessed during and after the intervention.
Results: In the chronic insomnia model, sustained caffeine exposure increased wakefulness, reduced quiet sleep, and disrupted sleep architecture during the light phase. It also increased anxiety-like behavior, impaired memory, elevated plasma corticosterone and inflammatory markers, activated wake-promoting hypothalamic neurons, and suppressed sleep-promoting neurons. Both the live probiotic and heat-treated postbiotic preparations ameliorated these abnormalities and improved autonomic regulation during sleep. Gut microbiota analysis showed that the live probiotic produced a more consistent microbial community structure across animals, whereas the heat-treated preparation had a less pronounced effect. In the AD study, APP/PS1 mice showed prolonged sleep latency, more frequent sleep interruptions, and lower delta power during quiet sleep, together with impaired self-care, greater anxiety-like behavior, and deficits in short- and long-term memory. The two-strain probiotic formulation shortened sleep latency, reduced anxiety-like behavior, enhanced spatial learning and memory, and decreased amyloid-beta deposition and neuroinflammation. Gut microbiota analysis showed that AD mice had greater individual variation in microbial composition, whereas probiotic treatment partially reduced this variability and promoted a more consistent microbial community structure. Conclusions: Across two distinct models of sleep disturbance, probiotic or postbiotic interventions improved sleep patterns, autonomic regulation, and behavioral outcomes while attenuating neuropathological changes. These improvements were accompanied by changes in gut microbial community structure, supporting further investigation of the gut–brain axis as a potential therapeutic target for chronic insomnia and AD-related sleep disturbance.

Keywords: chronic insomnia; Alzheimer's disease; sleep; autonomic regulation; probiotics; gut-brain axis; gut microbiota
2026年會: