Abstract
The antimicrobial peptides (AMP) produced by intestinal epithelial cells (IEC) play crucial roles in the regulation of intestinal homeostasis by controlling microbiota. Gut microbiota has been shown to promote IEC expression of RegIII3 and certain defensins. However, the mechanisms involved are still not completely understood. In this report, we found that IEC expression levels of RegIII 3 and β-defensins 1, 3, and 4 were lower in G protein-coupled receptor (GPR)43 '/' mice compared to that of wild-type (WT) mice. Oral feeding with short-chain fatty acids (SCFA) promoted IEC production of RegIII 3 and defensins in mice. Furthermore, SCFA induced RegIII 3 and β-defensins in intestinal epithelial enteroids generated from WT but not GPR43 '/' mice. Mechanistically, SCFA activated mTOR and STAT3 in IEC, and knockdown of mTOR and STAT3 impaired SCFA induction of AMP production. Our studies thus demonstrated that microbiota metabolites SCFA promoted IEC RegIII 3 and β-defensins in a GPR43-dependent manner. The data thereby provide a novel pathway by which microbiota regulates IEC expression of AMP and intestinal homeostasis.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 752-762 |
| Number of pages | 11 |
| Journal | Mucosal Immunology |
| Volume | 11 |
| Issue number | 3 |
| DOIs | |
| State | Published - May 1 2018 |
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ASJC Scopus subject areas
- Immunology and Allergy
- Immunology
Cite this
GPR43 mediates microbiota metabolite SCFA regulation of antimicrobial peptide expression in intestinal epithelial cells via activation of mTOR and STAT3. / Zhao, Ye; Chen, Feidi; Wu, Wei; Sun, Mingming; Bilotta, Anthony J.; Yao, Suxia; Xiao, Yi; Huang, Xiangsheng; Eaves-Pyles, Tonyia; Golovko, George; Fofanov, Yuriy; D'Souza, Warren; Zhao, Qihong; Liu, Zhanju; Cong, Yingzi.
In: Mucosal Immunology, Vol. 11, No. 3, 01.05.2018, p. 752-762.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - GPR43 mediates microbiota metabolite SCFA regulation of antimicrobial peptide expression in intestinal epithelial cells via activation of mTOR and STAT3
AU - Zhao, Ye
AU - Chen, Feidi
AU - Wu, Wei
AU - Sun, Mingming
AU - Bilotta, Anthony J.
AU - Yao, Suxia
AU - Xiao, Yi
AU - Huang, Xiangsheng
AU - Eaves-Pyles, Tonyia
AU - Golovko, George
AU - Fofanov, Yuriy
AU - D'Souza, Warren
AU - Zhao, Qihong
AU - Liu, Zhanju
AU - Cong, Yingzi
PY - 2018/5/1
Y1 - 2018/5/1
N2 - The antimicrobial peptides (AMP) produced by intestinal epithelial cells (IEC) play crucial roles in the regulation of intestinal homeostasis by controlling microbiota. Gut microbiota has been shown to promote IEC expression of RegIII3 and certain defensins. However, the mechanisms involved are still not completely understood. In this report, we found that IEC expression levels of RegIII 3 and β-defensins 1, 3, and 4 were lower in G protein-coupled receptor (GPR)43 '/' mice compared to that of wild-type (WT) mice. Oral feeding with short-chain fatty acids (SCFA) promoted IEC production of RegIII 3 and defensins in mice. Furthermore, SCFA induced RegIII 3 and β-defensins in intestinal epithelial enteroids generated from WT but not GPR43 '/' mice. Mechanistically, SCFA activated mTOR and STAT3 in IEC, and knockdown of mTOR and STAT3 impaired SCFA induction of AMP production. Our studies thus demonstrated that microbiota metabolites SCFA promoted IEC RegIII 3 and β-defensins in a GPR43-dependent manner. The data thereby provide a novel pathway by which microbiota regulates IEC expression of AMP and intestinal homeostasis.
AB - The antimicrobial peptides (AMP) produced by intestinal epithelial cells (IEC) play crucial roles in the regulation of intestinal homeostasis by controlling microbiota. Gut microbiota has been shown to promote IEC expression of RegIII3 and certain defensins. However, the mechanisms involved are still not completely understood. In this report, we found that IEC expression levels of RegIII 3 and β-defensins 1, 3, and 4 were lower in G protein-coupled receptor (GPR)43 '/' mice compared to that of wild-type (WT) mice. Oral feeding with short-chain fatty acids (SCFA) promoted IEC production of RegIII 3 and defensins in mice. Furthermore, SCFA induced RegIII 3 and β-defensins in intestinal epithelial enteroids generated from WT but not GPR43 '/' mice. Mechanistically, SCFA activated mTOR and STAT3 in IEC, and knockdown of mTOR and STAT3 impaired SCFA induction of AMP production. Our studies thus demonstrated that microbiota metabolites SCFA promoted IEC RegIII 3 and β-defensins in a GPR43-dependent manner. The data thereby provide a novel pathway by which microbiota regulates IEC expression of AMP and intestinal homeostasis.
UR - http://www.scopus.com/inward/record.url?scp=85048026863&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85048026863&partnerID=8YFLogxK
U2 - 10.1038/mi.2017.118
DO - 10.1038/mi.2017.118
M3 - Article
C2 - 29411774
AN - SCOPUS:85048026863
VL - 11
SP - 752
EP - 762
JO - Mucosal Immunology
JF - Mucosal Immunology
SN - 1933-0219
IS - 3
ER -