- 學位論文
腸道菌於卡洛里限制飲食提升記憶能力與帕金森氏症之研究
The Study of the Gut Microbiota in Calorie-restriction-induced Memory Enhancement and Parkinson’s Disease
摘要
腸道菌 (gut microbiota) 是腸道中微生物的總稱，其組成與週期性受外在刺激與宿主的調控，也能影響宿主的多種生理功能，包含代謝、免疫系統與神經系統等。過去研究發現，腸道菌相的組成受到宿主與外在環境的影響，如基因與飲食。每日飲食熱量即是一種外界刺激，卡洛里限制飲食 (calorie restriction) 過去被發現能影響腸道菌相與週期性，也能提升記憶能力，但其中的關聯性並不清楚。本研究利用抗生素處理 (antibiotic treatment) 與糞便微生物移植 (fecal microbiota treatment) 調控腸道菌相，結合次世代定序 (Next Generation Sequencing) 及多種行為測試，發現限制飲食熱量的方式，會藉由改變腸道菌的組成與週期性，而提升小鼠的記憶能力。 除了飲食，光線亦是一種外界刺激，可調控腸道菌的組成與週期性。我們將野生型小鼠與基因轉殖鼠 (Lrrk2G2019S)飼養於不同光照週期下，發現迴腸的表皮細胞參與光線對於腸道菌週期性調控之可能性。此外，我們將帕金森氏症 (Parkinson’s disease) 模式小鼠 (SNCAA53T) 飼養於異常的光照週期，發現腸道菌的改變早於行為病症病狀出現之前，且帕金森氏鼠與控制組小鼠的腸道菌相差異會隨著病症進展而增加。 整體而言，此研究證實了腸道菌於卡洛里限制飲食提升記憶能力之角色，也揭示腸道菌與帕金森氏症病人中突觸核蛋白 (α-synuclein) 異常沈積具雙向調控的可能性，更為宿主調控腸道菌週期性的機制提供新研究方向。
並列摘要
The composition and rhythmicity of the gut microbiota, referring to all microorganism in the gut, affects physiological functions of the host, such as metabolism, immune system, and nervous system. It has been shown that internal and external cues can both regulate the composition of the gut microbiota, such as the host genetic background and food intake, respectively. Calorie restriction (CR) is reported as one of the environmental cues to influence the composition and rhythmicity of the gut microbiota, as well as elevate memory with unknown mechanism. In this study, we showed that gut microbiota modulation such as antibiotics treatment or fecal microbiota transplantation could influence the memory enhancement effect in mice. Combining Next Generation Sequencing and several behavior tests, we validate that CR improves memory of mice via the modification on the gut microbial composition and rhythmicity. Besides, light is also an environmental cue, which influences the composition and rhythmicity of the gut microbiota. By keeping the WT and Lrrk2G2019S mice under different light-dark cycle, we demonstrate the epithelium cells in the ileum may potentially participate in the gut microbiota rhythmicity regulation via NOD2 pathway. Furthermore, our preliminary results showed that the gut microbial variation initiates before the presence of motor disability in SNCAA53T mice, a Parkinson’s disease (PD) mice model. And the gut microbial difference between PD and control mice increases with PD progression. Overall, our study validates the role of the gut microbiota in the CR-induced memory enhancement. We also demonstrate the possible reciprocal regulation between the gut microbiota and the aberrant α-synuclein accumulation in PD subjects. In addition, this study reveals a novel perspective in the regulation of the gut microbiota rhythmicity by the host.
參考文獻
延伸閱讀
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