- 學位論文
第2 型糖尿病人腸道微生物相及與GLP-1 RA 交互作用研究
Characterization of gut microbiota and its interactions with GLP-1 RA in type 2 diabetic patients
摘要
人類腸道微生物與宿主長期共演化在人類健康扮演重要的角色，一些疾病的發展證實和腸道微生物相不平衡有關，如近年來盛行率快速竄起的第2型糖尿病。過去橫斷性研究比較第2型糖尿病人、與健康人、及使用傳統藥物病人的腸道微生物相的差異，找出一些特定微生物與疾病發展有關，但部分研究觀察到的結果相反，因此不僅找出特定微生物與疾病狀態的關係，也需從生態的觀點探討微生態系裡核心腸道微生物群與宿主的交互影響，此外，只有部分研究有納入亞洲族群。為了處理這些問題，我們的研究在台灣林口長庚醫院取樣第2型糖尿病人。首先，比較使用新興糖尿病藥物第1型類升糖素胜肽受體促效劑(Glucagon-like peptide-1 receptor agonist，簡稱 GLP-1 RA)後，有療效與無療效反應兩群病人其腸道微生物相的特徵及差異，其次是探討病人用藥前後的腸道微生物相的變化，找出宿主-腸道微生物相-藥物在第2型糖尿病人的可能因果關係。本研究結果顯示有療效和無療效反應的腸道微生物相有顯著差異，但病人於GLP-1 RA用藥前後的腸道微生物相並無變化，推論第2型糖尿病人的腸道微生物組成與GLP-1 RA療效反應有關。無療效反應的病人可能有微生態失調(dysbiosis)，包括具有高豐度的微生物群，如，戴阿利斯特桿菌屬(Dialister)、戴阿里斯氏屬(Alistipes)、病毒丁酸單胞菌(Butyricimonas virosa)、光岡菌屬(Mitsuokella)及莫亞拉屬(Moryella)，以及失去或減少核心微生物群，糞桿菌屬(Faecalibacterium)、厭氧棒狀菌屬(Anaerostipes)、糞球菌屬(Coprococcus)及布勞特氏菌屬(Blautia)。我們的發現將有助於預測糖尿病人對於GLP-1 RA的療效反應，使健康照護者提供病人個人化治療選項。
並列摘要
The Human gut microbiota which co-evolved with the host plays an important role in human health. Evidence has showed that the imbalance in the microbial community is associated with the development of some diseases such as type 2 diabetes (T2D), of which prevalence has been rising rapidly in recent years. Previous cross-sectional and comparison studies had characterized the difference in gut microbiota between T2D patients, and healthy people, as well as T2D patients who received traditional treatment. Some specific microbes which may be linked to disease development were identified, however several studies observed opposite results for these specific microbes. Therefore, there is a need to take an ecological view of gut microbiota in this micro-ecosystem, to investigate relationships not only between several microbes and a diseased state but also a cluster of core gut microbiota and their interactions with the host. Furthermore, limited work was done in Asian populations. Thus, our studies to address these questions and to sample a set of T2D patients were conducted at Chang Gung Memorial Hospital, Taiwan. Firstly, we characterized and compared gut microbiota of T2D patients who had a response or non-response to an emerging anti-diabetic drug, Glucagon-like peptide-1 receptor agonist (GLP-1 RA) after treatment. Secondly, we explored the gut microbiota changes between before and after patients taking GLP-1 RA, and to identify potential casual relationships of host-microbiota-drug interactions in T2D patients. This study results showed that gut microbiota significantly differed between responders and non-responders but no change before and after taking GLP-1 RA, which suggested that the microbial composition in T2D patients were associated with treatment response to GLP-1 RA. Non-responders may have gut microbiota dysbiosis, including harbored high abundance of identified microbial features, e.g., Dialister, Alistipes, Butyricimonas virosa, Mitsuokella and Moryella, and lost or decreased abundance of core genera Faecalibacterium, Anaerostipes, Coprococcus and Blautia. Our findings may be helpful for predicting T2D patients’ responses to GLP-1 RA, enabling healthcare providers to offer personalized treatment options to patients.