Article ; Online: Transplant of microbiota from Crohn's disease patients to germ-free mice results in colitis.
2024 Volume 16, Issue 1, Page(s) 2333483
Abstract: Although the role of the intestinal microbiota in the pathogenesis of inflammatory bowel disease (IBD) is beyond debate, attempts to verify the causative role of IBD-associated dysbiosis have been limited to reports of promoting the disease in ... ...
Abstract | Although the role of the intestinal microbiota in the pathogenesis of inflammatory bowel disease (IBD) is beyond debate, attempts to verify the causative role of IBD-associated dysbiosis have been limited to reports of promoting the disease in genetically susceptible mice or in chemically induced colitis. We aimed to further test the host response to fecal microbiome transplantation (FMT) from Crohn's disease patients on mucosal homeostasis in ex-germ-free (xGF) mice. We characterized and transferred fecal microbiota from healthy patients and patients with defined Crohn's ileocolitis (CD_L3) to germ-free mice and analyzed the resulting microbial and mucosal homeostasis by 16S profiling, shotgun metagenomics, histology, immunofluorescence (IF) and RNAseq analysis. We observed a markedly reduced engraftment of CD_L3 microbiome compared to healthy control microbiota. FMT from CD_L3 patients did not lead to ileitis but resulted in colitis with features consistent with CD: a discontinued pattern of colitis, more proximal colonic localization, enlarged isolated lymphoid follicles and/or tertiary lymphoid organ neogenesis, and a transcriptomic pattern consistent with epithelial reprograming and promotion of the Paneth cell-like signature in the proximal colon and immune dysregulation characteristic of CD. The observed inflammatory response was associated with persistently increased abundance of |
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MeSH term(s) | Humans ; Mice ; Animals ; Crohn Disease/microbiology ; Clostridioides difficile ; Gastrointestinal Microbiome ; Colitis ; Microbiota ; Fecal Microbiota Transplantation ; Dysbiosis/microbiology |
Language | English |
Publishing date | 2024-03-27 |
Publishing country | United States |
Document type | Journal Article |
ZDB-ID | 2575755-6 |
ISSN | 1949-0984 ; 1949-0984 |
ISSN (online) | 1949-0984 |
ISSN | 1949-0984 |
DOI | 10.1080/19490976.2024.2333483 |
Database | MEDical Literature Analysis and Retrieval System OnLINE |
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