Abstract
摘要:腸道菌叢發出的訊息對於免疫系統的發育極為重要,腸道菌叢的改變會使得免疫失調,導致過敏及自體免疫疾病。在此整合計畫中,我們將分別以孩童特發性關節炎、原發性膽汁性膽管炎和異位性皮膚炎為研究的對象,以瞭解是否這些微生物菌叢是否與患者或是動物模式的發炎相關,或是與免疫調節的機轉有關。而在異位性皮膚炎的患嬰也將分析皮膚和母乳的微生物菌叢,此外母親的飲食是否與母乳的微生物菌叢是否有關,也進一步影響到異位性皮膚炎的疾病發生。以分析病人檢體及使用動物模式的方式探討微生物菌叢在免疫疾病包括原發性膽汁性膽管炎(PBC),兒童特發性關節炎(JIA)及嬰兒的異位性皮膚炎(AD)的免疫調節機轉。子計畫一:腸道菌叢在兒童特發性關節炎角色之研究:孩童特發性關節炎以機轉來說,是一種慢性的發炎疾病,目前對真正的致病機轉仍不是很清楚。所以我們將釐清不同分型及不同疾病程度的JIA的關係,進一步探討不同治療藥物對JIA的腸道菌叢的影響,再以疾病動物模式探討腸道菌叢在JIA之病理角色。 子計畫二:腸道菌叢在引起原發性膽汁性膽管炎角色之研究:由於目前有愈來愈多的證據顯示引起原發性膽汁性膽管炎的抗粒腺體抗體(anti-mitochrondral antibodies, AMA)的產生與腸道細菌有關,所以利來進行腸道微生物菌相與免疫調節之間的關係。我們將探討正常腸道菌叢的改變是否影響或引發PBC,進一步鑑定此特殊的微生物菌種以及探討腸道菌叢的改變影響或引發PBC的細胞及分子機轉。子計畫三:微生物菌叢對嬰兒異位性皮膚炎之影響:我們將開始出生世代研究的收案及分析異位性皮膚炎嬰兒食用的母乳的成分、親餵母親胸部皮膚微生物菌叢、以及AD嬰兒的腸道菌叢與正常嬰兒的差異,並且我們將已先前建立之異位性皮膚炎的動物模式探討其機轉。子計畫四:微生物菌叢資料分析和鑑定:目前研究微生物菌叢最大的癥結在於進行這些相關的資料分析,並進一步鑑定甚至分離這些在統計上有意義的微生物,所以需要一個能夠進行這方面分析的核心子計畫是此一整合計畫不可或缺的。所以,此一整合計畫我們結合臨床免疫疾病的臨床醫師、基礎免疫學研究的老師、專長營養免疫的研究者和專長於微生物研究的學者,可以讓我們對腸道、皮膚和甚至母乳的微生物菌叢與發炎反應和免疫調控之間的相關性有更清楚的了解。
Abstract: Signals derived from gut microbiota are critical for the development of the immune system and alterations of these gut microbial communities can cause immune dysregulation, leading to allergies and autoimmune disorders. It has been suggested that intestinal microbiota was correlated with inflammatory process and immune regulation in a variety of immunological diseases. In this integrated project, we like to clarify the role of microbiota in immunological diseases including primary biliary cholangitis (PBC), juvenile idiopathic arthritis (JIA), and infantile atopic dermatitis (AD) by analyzing patients’ samples and disease mouse models. Sub-project 1: The role of gut microbiome in juvenile idiopathic arthritis: Juvenile idiopathic arthritis has been found to be associated with chronic inflammatory responses of the joints and systemic organs. We will identify the association between gut microbiome and juvenile idiopathic arthritis of different subtypes and different disease activity, clarify the effects of therapeutic agents (DMARDs or TNF-αinhibitor) on gut microbiome in juvenile idiopathic arthritis, and explore the pathogenic role of gut microbiome in juvenile idiopathic arthritis by mouse model. Sub-project 2: The role of gut microbiota in the initiation of primary biliary cholangitis: It has been documented that anti-mitochondral antibodies (AMA) are correlated with the development of primary biliary cholangitis. Further, the development of AMA has been found to be associated with intestinal bacteria. We will assess whether and how modification of normal gut commensal microflora would influence the induction and development of PBC, identify specific species of microbiome in the development of PBC and clarify the mechanisms of how the modification of gut microbiota affects PBC development. Sub-project 3. The influence of microbiome on infantile atopic dermatitis: Intestinal microbiota has bee suggested to be critical in the pathogenesis of atopic dermatitis. In addition, nutrient composition of breast mile has been found to be very important in the development of atopic dermatitis. We will conduct a prospective study to determine the differences of components in the breast milk, the differences of skin microbiota from mother’s breast, and also the differences of intestinal micriobiota between AD and healthy infants, and use our established mouse model of AD for the mechanical study.Sub-project 4. Core unit for the analysis and identification of microbiota. Methods to assess and define the profile of microbiota such as next generation sequence has been developed with success. However, the most important work in the project actually is the core group to analyze the data derived from the next generation sequence and also identify the species of bacteria. We like to establish the core unit in this integrated project for the future experiments. In this integrated project, we included experienced physicians expertise at immunological diseases, well-trained basic immunologist, researcher of nutritional immunologist and microbiologist to collaborate in the project. We believe that this study will not only allow us to understand the pathogenesis of PBC, JIA, and infantile AD but will also provide us new foundations for the design of novel immuno- or microbe- based therapies.
Keyword(s)
微生物菌叢
免疫疾病
原發性膽汁性膽管炎
兒童特發性關節炎
異位性皮膚炎
microbiota
immunological disease
primary biliary cholangitis
juvenile idiopathic arthritis
atopic dermatitis