Establishment of Human Organoid Lines as a Tool to Dissect Molecular Pathways of Host-microbiota Interactions
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 100
- 试验地点
- 1
- 主要终点
- Host-Microbiota interaction - Stem cell maintenance and Cell Differentiation
研究概览
简要总结
The human body inhabits a complex consortium of different microbes which together form the microbiota. Virtually every surface of the human body is colonized by a distinct microbiota, forming complex communities. An increasing number of research results indicates that changes in the microbiota can have vast effects on the health of its host.
Most studies investigating the microbiota were conducted on animals, as many interventions and investigations cannot be performed on humans due to ethical considerations. This raises the question if findings from experimental studies are translational and can benefit patients. That becomes especially apparent when trying to dissect molecular mechanisms involved in this fine-tuned interplay between nutrients, the microbiota, and its host.
By establishing human organoid cultures from the large and small intestine that can be exposed to microbes and/or microbial products with subsequent transcriptomic, epigenetic and immunological analysis, the investigators aim to generate findings with high translational potential with new insights into the complex interaction of the microbiota, the host and its immune system.
详细描述
- Data obtained from participants will be recorded in the database Redcap to ensure high-quality data recording
- Establishment of human organoid cultures are standardized by published protocols (Pleguezuelos-Manzano et al. 2020)
研究设计
- 研究类型
- Observational
- 观察模型
- Case Only
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Signed informed consent
- •Indication for upper or lower endoscopic procedure
- •Ability to understand and follow study procedures and understand informed consent
- •Age 18-80 years
- •Negative pregnancy test result prior to study enrollment of female study participants (test will be performed prior to enrollment)
- •BMI between 18.5 and 30 kg/m2
排除标准
- •Disease known to chronically affect gut microbiota, gut epithelium or gut-associated immune system, namely inflammatory bowel disease, diverticulitis, microscopic colitis, liver cirrhosis, malignancy within the digestive tract, systemic sclerosis, coeliac disease, common-variable immunodeficiency, diabetes mellitus
- •Medication with immunosuppressants (e.g. corticoids, biological therapy)
- •Current diagnosis of a hematological disorder (e.g. anemia with hemoglobin <7 g/dl, leukemia) or any other absolute contraindication for blood draw
- •Women who are pregnant
- •Serious coagulation disorder, relevant thrombocytopenia (<50'000/ul), double platelet-inhibition, oral anticoagulation (ASS therapy is possible)
- •Known or suspected non-compliance, drug, or alcohol abuse
- •Inability to follow the procedures of the study, e.g., due to language problems, psychological disorders, dementia, etc. of the participant
- •Previous enrolment into the current study
- •Enrolment of the investigator, his/her family members, employees, and other dependent persons
- •Inability or unwillingness to provide blood samples and tissue samples (biopsies)
- •Participants taking oral anticoagulant or with bleeding disorders who would be at much higher risk of bleeding after biopsy samples or who are contraindicated for an endoscopic examination
- •Patients unable to give informed consent
- •Patients that have been under antibiotic therapy in the last 4 weeks
- •Participation in other clinical study interfering with study procedures
- •Potential study participants that wish not to be informed about random results acquired during the study (e.g., during endoscopy or genetic analysis) relevant for their health and for prevention of diseases
结局指标
主要结局
Host-Microbiota interaction - Stem cell maintenance and Cell Differentiation
时间窗: 3 Years
Determining effects of microbial-derived metabolites on epithelial cell differentiation and stem cell maintenance
Transcriptomic and Epigenomic Landscape of host-microbiota Interaction
时间窗: 3 Years
Determining effects of microbial-derived metabolites on the transcriptomic and epigenomic landscape of human organoids treated with the respective metabolite
Assessment of changes in the transcriptomic profile of epithelial cells before and after organoid culture
时间窗: 3 Years
Assessment of changes in the transcriptomic profile of epithelial cells before and after organoid culture is established by RNA-sequencing and quantitative polymerase chain reaction (qPCR)
Assessment of changes in the epigenome of epithelial cells before and after organoid culture
时间窗: 3 Years
Assessment of changes in the epigenome of epithelial cells before and after organoid culture is established by whole genome bisulphite sequencing and chromatin immunoprecipitation sequencing
次要结局
- Gut-on-a-chip(3 Years)
- 3D-to-2D Transwell System(3 Years)