Dietary Interventions Ameliorate Infectious Colitis by Restoring the Microbiome and Promoting Stem Cell Proliferation in Mice
| Autor: | Ishfaq Ahmed, Kafayat Yusuf, Badal C. Roy, Jason Stubbs, Shrikant Anant, Thomas M. Attard, Venkatesh Sampath, Shahid Umar |
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| Rok vydání: | 2021 |
| Předmět: |
lgr5
Transcription Genetic QH301-705.5 colitis gut microbiome Article short-chain-fatty-acids (SCFAs) Epithelium Catalysis Receptors G-Protein-Coupled intestinal stem cells Citrobacter rodentium Pectin Tributyrin bacterial infection dietary intervention Inorganic Chemistry Animals Humans Regeneration Biology (General) Physical and Theoretical Chemistry Promoter Regions Genetic QD1-999 Molecular Biology Triglycerides Spectroscopy Cell Proliferation Mucin-2 Gene Expression Profiling Microbiota Stem Cells Organic Chemistry Enterobacteriaceae Infections Biodiversity General Medicine Diet Computer Science Applications Mice Inbred C57BL Chemistry Butyrates HEK293 Cells Gene Expression Regulation Fermentation Pectins |
| Zdroj: | International Journal of Molecular Sciences; Volume 23; Issue 1; Pages: 339 International Journal of Molecular Sciences International Journal of Molecular Sciences, Vol 23, Iss 339, p 339 (2022) |
| ISSN: | 1422-0067 |
| DOI: | 10.3390/ijms23010339 |
| Popis: | Decreases in short-chain-fatty-acids (SCFAs) are linked to inflammatory bowel disease (IBD). Yet, the mechanisms through which SCFAs promote wound healing, orchestrated by intestinal stem cells, are poorly understood. We discovered that, in mice with Citrobacter rodentium (CR)-induced infectious colitis, treatment with Pectin and Tributyrin diets reduced the severity of colitis by restoring Firmicutes and Bacteroidetes and by increasing mucus production. RNA-seq in young adult mouse colon (YAMC) cells identified higher expression of Lgr4, Lgr6, DCLK1, Muc2, and SIGGIR after Butyrate treatment. Lineage tracing in CR-infected Lgr5-EGFP-IRES-CreERT2/ROSA26-LacZ (Lgr5-R) mice also revealed an expansion of LacZ-labeled Lgr5(+) stem cells in the colons of both Pectin and Tributyrin-treated mice compared to control. Interestingly, gut microbiota was required for Pectin but not Tributyrin-induced Lgr5(+) stem cell expansion. YAMC cells treated with sodium butyrate exhibited increased Lgr5 promoter reporter activity due to direct Butyrate binding with Lgr5 at −4.0 Kcal/mol, leading to thermal stabilization. Upon ChIP-seq, H3K4me3 increased near Lgr5 transcription start site that contained the consensus binding motif for a transcriptional activator of Lgr5 (SPIB). Thus, a multitude of effects on gut microbiome, differential gene expression, and/or expansion of Lgr5(+) stem cells seem to underlie amelioration of colitis following dietary intervention. |
| Databáze: | OpenAIRE |
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