臺灣博碩士論文加值系統

中風為中樞神經系統因血管損傷而導致的急性局部神經功能缺損，其位居全球十大死因中第二位，所伴隨之高失能比例也造成社會負擔的增加。中風會導致認知功能障礙、運動損傷、營養不良等併發症，此外也會使腸道菌相失衡。過去研究指出龍根菌 (Bifidobacterium longum) 有改善認知功能、運動表現及增加腸道菌相豐富度等作用，但對於中風患者補充龍根菌之影響尚未確認。本研究目的探討補充龍根菌OLP-01 (Bifidobacterium longum OLP-01) 對中風患者認知功能、運動表現、營養狀態及腸道菌相之影響。本研究為單盲隨機對照試驗，招募22位中風患者，隨機分至OLP-01組 (n=12) 與安慰劑組 (n=10)，連續12週每日補充劑量2 × 1010 colony-forming unit (CFU) 龍根菌OLP-01或安慰劑。結果顯示OLP-01組顯著增加蒙特利爾認知評估量表分數、減少路徑描繪測驗時間及增加史楚普叫色測驗非一致 (incongrument) 正確率，並能改變腸道菌相組成，營養狀態部分顯示迷你營養評估量表分數顯著下降，但介於無營養不良狀態，運動表現顯示安慰劑組顯著增加六分鐘行走測驗距離。本研究顯示中風患者連續12週補充2 × 1010 CFU的龍根菌OLP-01後能提升中風患者認知功能，並可能與影響腸道菌相組成改變具有潛在關係。

Stroke is a syndrome of acute, focal neurological deficit attributed to vascular injury of the central nervous system. It was the 2nd leading cause of death worldwide and accompanied by high disability rate also increases the social burden. Stroke can lead to some complications such as cognitive dysfunction, motor impairment, malnutrition, and also gut dysbiosis. Some previous study showed that Bifidobacterium longum could improve cognitive function, exercise performance and change the abundance of gut microbiota. However, the effects of Bifidobacterium longum OLP-01 among stroke patients are still unknown. This study was to investigate that the effects of Bifidobacterium longum OLP-01 on cognitive function, physical performance, nutritional status and gut microbiota in stroke patients. This study was a single blind, randomized, placebo-controlled trial. We recruited 22 stroke patients and allocated to supplement with either 2 × 1010 colony-forming unit (CFU) of Bifidobacterium longum OLP-01 powder per day (OLP-01 group, n=12) or placebo (placebo group, n=10) for 12 weeks. After 12 weeks of supplementation, the Montreal cognitive assessment (MoCA) score was significantly increased, the complete time of trail making tests (TMTs) A and B was significantly decreased, and correct percentage of incongruent in Stroop color naming test was significantly increased in OLP-01 group. The gut microbiota also showed significant differences between groups. Mini nutritional assessment (MNA) score showed significantly decreased in OLP-01 group but was within normal ranges. Physical performance showed significantly increased distance of 6-min walking test in placebo group. This study suggested that the supplementation of Bifidobacterium longum OLP-01 for 12 weeks could improve cognitive functions which might have the potential with the changes of gut mictobiota in stroke patients.

中文摘要 I
Abstract II
致謝 IV
圖目次 IX
表目次 X
第一章 緒論 1
第二章 文獻回顧 2
第一節 中風之介紹 2
第二節 中風之生理機制及臨床症狀 4
第三節 中風流行病學資料 6
第四節 中風的治療 7
第五節 認知功能與中風之關係 9
第六節 運動表現與中風之關係 11
第七節 營養狀態與中風之關係 12
第八節 腸道菌相與中風之關係 14
第九節 益生菌與腸道菌相之調節作用 16
第十節 龍根菌之相關研究 19
第十一節 研究動機與目的 22
第三章 實驗設計與材料方法 23
第一節 實驗設計 23
一、受試者招募條件與人數 23
二、受試者分組 26
三、實驗介入物 26
四、實驗流程 29
五、受試者生活型態、飲食、復健運動及用藥習慣之管理 30
六、受試者依從度之管理 30
第二節 檢測項目與方法 31
一、體位、身體組成及血壓測量 31
二、血液生化檢測 31
三、腸道菌相分析 34
四、認知功能評估 35
五、運動表現評估 37
六、迷你營養評估量表 38
七、三日飲食記錄 38
第三節 統計分析 39
第四章 結果 40
第一節 受試者依從度 40
第二節 受試者基本資料與中風相關特徵 40
一、受試者基本資料 40
二、受試者中風相關特徵 41
第三節 受試者體位測量、身體組成與血壓 44
一、體位測量 44
二、身體組成 46
三、血壓 49
第四節 受試者營養狀態 52
第五節 受試者血液生化分析 55
一、蛋白質營養狀態指標 55
二、血脂相關指標 56
三、血糖相關指標 57
四、C-反應蛋白 58
五、血球計數指標 60
六、細胞激素 60
第六節 受試者認知功能 64
一、MoCA測驗 64
二、TMTs與Stroop color naming test測驗 66
第七節 受試者運動表現 71
一、TUGT測驗 71
二、六分鐘行走測驗 71
第八節 受試者營養素攝取 73
一、熱量、三大營養素及膳食纖維攝取量 73
二、維生素攝取量 76
三、礦物質攝取量 78
第九節 受試者腸道菌相分析 80
一、相對豐富度與LEfSe分析 80
二、α-多樣性 81
三、β-多樣性 81
第五章 討論 95
第一節 中風患者體位、身體組成及血壓 95
第二節 中風患者營養狀態 97
第三節 中風患者血糖、血脂指標及血球計數 99
第四節 中風患者認知功能 101
第五節 中風患者運動表現 104
第六節 中風患者腸道菌相 106
第七節 研究優勢與限制 111
第六章 結論 112
第七章 參考文獻 113
附錄一、TMU-JIRB通過證明函 122
附錄二、疾病史、用藥習慣及生活習慣問卷 123
附錄三、蒙特利爾認知評估量表 125
附錄四、史楚普叫色測驗 126
附錄五、路徑描繪測驗 127
附錄六、迷你營養評估量表 129


圖目次
圖一、益生菌對於腸-腦軸之調控機制 18
圖二、Bifidobacterium longum於顯微鏡下影像 21
圖三、實驗流程圖 25
圖四、龍根菌OLP-01產品分析 28
圖五、龍根菌OLP-01對於中風受試者菌門相對豐富度之影響 82
圖六、龍根菌OLP-01對於中風受試者菌綱相對豐富度之影響 83
圖七、龍根菌OLP-01對於中風受試者菌科相對豐富度之影響 84
圖八、龍根菌OLP-01對於中風受試者菌屬相對豐富度之影響 85
圖九、安慰劑組受試者之組內LEfSe分析 86
圖十、OLP-01組受試者之組內LEfSe分析 87
圖十一、安慰劑組與OLP-01組受試者之組間LEfSe分析 88
圖十二、龍根菌OLP-01對於中風受試者α-多樣性之影響 89
圖十三、龍根菌OLP-01對於中風受試者β-多樣性在unweighted UniFrac distance之影響 90
圖十四、龍根菌OLP-01對於中風受試者β-多樣性在weighted UniFrac distance之影響 91
圖十五、龍根菌OLP-01對於中風受試者β-多樣性在variance adjusted weighted UniFrac distance之影響 92
圖十六、龍根菌OLP-01對於中風受試者β-多樣性在GUniFrac distance之影響 93
圖十七、龍根菌OLP-01對於中風受試者β-多樣性在Bray-Curtis distance之影響 94


表目次
表一、中風之危險因子 3
表二、介入物之營養成分 27
表三、中風患者之基本資料 42
表四、中風患者之中風相關特徵 43
表五、中風患者之體位測量與身體組成 48
表六、中風患者之血壓與脈搏 51
表七、中風患者之營養狀態 54
表八、中風患者之營養狀態、血脂、血糖及C-反應蛋白血液生化指標 59
表九、中風患者之血球計數指標 62
表十、中風患者之血液細胞激素 63
表十一、中風患者之蒙特利爾量表認知評估 65
表十二、中風患者之路徑描繪測驗與史楚普叫色測驗 70
表十三、中風患者之運動表現 72
表十四、中風患者之熱量、三大營養素及膳食纖維攝取量 75
表十五、中風患者之維生素攝取量 77
表十六、中風患者之礦物質攝取量 79

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