Human Intestinal Organoid as model for Alcohol Use Disorder (AUD)
Scope of the method
- Human health
- Basic Research
- Translational - Applied Research
- In vitro - Ex vivo
- Human derived cells / tissues / organs
- Human Intestinal Organoid
- Gut epithelium Organoid
- Alcohol Use Disorder (AUD)
- Human Stem cells
More than 3 million deaths worldwide are linked to excessive alcohol consumption. Alcohol abuse associated gut barrier dysfunction is thought to play an important role in the development of alcohol-associated liver disease. Although some aspects that contribute to this process have been elucidated, the role of intestinal epithelium, a major component of the gut barrier, and its alterations in gut barrier failure in Alcohol Use Disorder (AUD) remain poorly understood. Our preliminary data on duodenal epithelium in humans showed a disturbed proliferation-differentiation process in AUD patients. In this project, Intestinal Organoids (Enteroids) are used to model this disease. The Enteroids are generated from crypts originating from control and patient’s duodenum biopsies. Interestingly, they are able to growth, differentiate and later display crypt and villi architecture mimicking in vivo condition. In addition, they keep their host phenotype in culture during first passages allowing us to study the different alterations occurring in the host epithelium. Moreover, we could determine the gene expression of differentiated epithelial cells represented in the model.
Cell culture incubator, Laminar Flow, Hood.
- Still in development
Pros, cons & Future potential
Intestinal organoids recapitulate more closely the in vivo architecture and can reproduce some special functions for instance mucus production. They keep their host phenotype which is a major advantage in studying and understanding a disease.
Time is a limiting factor since Intestinal Organoids grow and differentiate in two weeks. Additionally, the phenotype is lost after several passages.
Human Intestinal Organoid can be used to study Microbiota and the Intestinal Epithelium interactions. Colon Organoids could be used to study Crohn's disease.
References, associated documents and other information
Mahe MM, Aihara E, Schumacher MA, Zavros Y, Montrose MH, Helmrath MA, Sato T, Shroyer NF. Establishment of Gastrointestinal Epithelial Organoids. Curr Protoc Mouse Biol. 2013. 3(4):217-40. DOI: 10.1002/9780470942390.mo130179.
Lin M, Hartl K, Heuberger J, et al. Establishment of gastrointestinal assembloids to study the interplay between epithelial crypts and their mesenchymal niche. Nat Commun. 2023. 14(1):3025. DOI:10.1038/s41467-023-38780-3
Qu M, Xiong L, Lyu Y, et al. Establishment of intestinal organoid cultures modeling injury-associated epithelial regeneration. Cell Res. 2021. 31(3):259-271. DOI:10.1038/s41422-020-00453-x
Contact personAmi Gloria Toulehohoun
OrganisationsUniversité Catholique de Louvain (UCL)