2018-01-012024-05-13https://scholars.lib.ntu.edu.tw/handle/123456789/648341摘要：隨著基因體解序及健康大數據來臨，科學家因此握有疾病解密的鑰匙，並極可能創造新預防與治療方式。因應第二基因體微生物叢、新興代謝疾病、感染症的崛起，臨床、基礎與資訊專家主動組成團隊科學，提出三項子計畫來發展微生物叢體與總體基因體學分析平台，期待解析疾病關聯性，探究微生物叢與健康、疾病及治療的關係與應用，先導主題共同以愛滋病毒感染者腸內菌叢變化來建立微生物培養體學與宏基因體學，並延伸至生殖醫學與過敏兒之臨床低基因性難題。計畫人員跨台大醫院、醫與電資學院，具各自領域專長，亦長期密切合作，並服務於相關核心實驗室、溝通良好，三項子計畫如下：一、探討愛滋病毒感染者接受高效能抗病毒療法前後腸內微菌變化與免疫重建之相關性，以提昇療效二、發展微生物培養體學在微生物叢醫學與疾病關聯性的解析及應用，企圖解決人工生殖低受孕率問題三、發展使用者容易操作的線上分析總體基因體學平台及健康台灣民眾之菌相資料庫 緊密結合微生物培養體學及宏基因體學兩類分析方法，確定其與健康和疾病的動態關係、優化其對個人化診斷學和醫學，提供未滿足需求新治療、預防策略，為人體微生物叢、健康促進與疾病的機制研究、應用及產業活絡帶來重大影響。<br> Abstract: After the first human genomes were sequenced and scientists felt they were delivered the abilities to unlocking numerous puzzles about disease. However, there are still low genetic penetrance health conditions, such as emergent infectious diseases, modern metabolic disorders, remain as urgent unmet clinical needs. Notably, with the recognition of microbiota as the human 2nd genome and it intimate relations with our health/disease states, microbita might offer the last piece of the puzzle to personalized healthcare. Toward this goal and with a team science approach consist of competent clinician, basic, information scientists and microbiologists, we aim to develop analytic platforms, including sequencing, culturomics and identification ones, for microbiota and metagenomics to scrutinize first the disease association and then clinical applications. A microbita dysbiosis has been demonstrated to lead to diseases of many organs and systems, such as respiratory, gastrointestinal, hepatic, metabolic, and cardiovascular systems. Nevertheless, gut microbiota and the dynamic immune system of HIV-infected patients remain unclear. Specific commensal species were reported to contribute to immune activation during HIV infection and correeponding malfunction of intestinal immune barrier, translocation of immune-stimulatory microbial products, and chronic systemic inflammation are thought to drive disease progression of AIDS. Each patient indeed leads to different clinical courses with the highly active anti-retroviral therapy (HAART) and responses with discrete immune profiles. We thus hypothesize the mis-regulation of immunopathology in patients relies on his/her own gut microbiota signatures those cross-talk with the intestinal immunity then circulate to impact the whole body. Here, we will focus on exploring the relation between the gut microbiota signature changes and the dynamic immune profiles of HIV-infected patients during the anti-retroviral therapy as an initiative and three centralized subprojects are as the followings:Subproject 1: The modulation of gut microbiota and immune reconstitution among HIV-infected patients receive highly active anti-retroviral therapy – This subproject is consist of excellent clinician scientists aiming to provide a NGS service and genomic approaches platform as well as to identify of unmet clinical needs and providing clinical consultations. In cooperation with subproject 3, the alteration of gut microbiota in HIV-infected patients will be revealed. With supports from Subproject 2, the beneficial and/or unfavorable bacteria of HIV-infected patients receiving HAART treatment will also be identified.Subproject 2: Development and Application of Microbial Culturomics in the Analysis of Microbiota and Disease Relation – By bringing the expertise in microbial culturomics, MALDI-TOF MS and in vitro fertilization, this Subproject 2 focuses first on the isolation of previous identified infant allergy-causing R. gnavus and the potential beneficial and/or causative bacteria isolated from Subproject 1. Then the platform might then extend to solve the poor success pregnant rate of IVF-ET treatment.Subproject 3: Development of a user-friendly online analytic platform for metagenomics data and database for healthy individuals in Taiwan – A group of experienced researchers in the fields of bioinformatics and metagenomics will provide the bioinformatcs and metgenomic analytic pipelines for this pioneering project. With trainings of the dataset from subprojects, the Subproject 3 aims to establish a user-friendly online analytic platform for metagenomics data.愛滋病人類免疫不全病毒感染腸內微菌免疫微生物培養體學宏基因體學MALDI-TOF質譜儀總體基因體學線上分析平台資料庫HIVAIDSGut microbiotaImmunityCulturomicsMetagenomicsMatrix-assisted laser desorption ionization-tie of flight mass spectrometrymetagenomicsonline analytic platformdatabase