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Published on: January 5, 2017
Intestinal epithelial SETD2 maintains gut microbial homeostasis to attenuate colitis
Jing Feng1,2,3, Ziyi Wang4,5, Yue Xu4,5
1Department of Gastroenterology, Shanghai Ninth People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
The epigenetic regulator SET domain containing 2 (SETD2) is crucial for maintaining gut microbial balance. SETD2 deficiency disrupts this balance, leading to colitis, but restoring healthy gut microbiota can improve the condition.
Area of Science:
- Epigenetics
- Microbiome research
- Gastroenterology
Background:
- Inflammatory bowel disease (IBD) pathogenesis involves disrupted host-microbiota homeostasis.
- Epigenetic modifications influence gut microbial composition.
- The role of SET domain containing 2 (SETD2) in intestinal microbial ecology and colitis is unknown.
Purpose of the Study:
- Investigate SETD2's role in maintaining gut microbial homeostasis.
- Determine SETD2's function in modulating colitis progression.
Main Methods:
- Utilized RNA-seq, ATAC-seq, and CUT&Tag-seq on colonic epithelial cells from SETD2 knockout mice.
- Analyzed fecal samples using 16S rRNA sequencing and metabolomics.
- Performed molecular experiments and fecal microbiome transplantation.
Main Results:
- SETD2 deficiency caused Reg3 lectin overproduction and altered gut microbiota.
- Beneficial bacteria decreased, and dysregulated metabolites accumulated in SETD2-deficient mice.
- Gut microbiota transplantation ameliorated colitis severity.
Conclusions:
- SETD2 plays a previously unrecognized role in maintaining microbial homeostasis.
- Epigenetic regulation by SETD2 preserves intestinal homeostasis.
- Findings suggest novel therapeutic strategies for IBD.
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