Aryl hydrocarbon receptor/IL-22/Stat3 signaling pathway is involved in the modulation of intestinal mucosa antimicrobial molecules by commensal microbiota in mice.
Aryl hydrocarbon receptor/IL-22/Stat3 signaling pathway is involved in the modulation of intestinal mucosa antimicrobial molecules by commensal microbiota in mice.
复制标题
DOI：
10.1177/1753425918785016
复制
发表时间：
2018-07
期刊：
影响因子：
3.2
通讯作者：
Wang X
中科院分区：
文献类型：
--
作者：
Wang J;Wang P;Tian H;Tian F;Zhang Y;Zhang L;Gao X;Wang X
令人信服的证据证明了共生微生物群在宿主生理中的关键作用以及抗生素治疗后其扰动的有害影响。然而，共生菌群对肠道黏膜抗菌分子的影响尚未得到系统的阐明。在这里，我们研究了抗生素诱导的肠道菌群耗竭和随后的肠道菌群恢复对小鼠肠道黏膜中抗菌分子的影响。我们的研究结果表明，共生微生物群的消耗导致肠黏膜萎缩和抗菌分子的减少，包括溶菌酶、再生胰岛衍生蛋白3 γ (RegIIIγ)和隐tdin 5mrna，而随后通过粪便微生物群移植（FMT）重建肠道微生物群可以恢复粘膜形态和抗菌药物。重要的是，我们的研究表明，芳烃受体（AhR）、白细胞介素-22 （IL-22）和磷酸化Stat3 （p-Stat3）的下调与抗菌素减少有关，这可能介导抗生素相关的肠黏膜损伤。最后，AhR激动剂6-甲酰基林多洛（3,2-b）咔唑（Ficz）外源激活AhR/IL-22/Stat3信号通路，使抗生素治疗后的抗菌分子水平显著恢复到与FMT重建肠道微生物群后的水平相似。总之，我们的研究结果表明，AhR/IL-22/Stat3信号通路参与了共生菌群对肠黏膜抗菌分子的调节，并表明该途径是治疗抗生素相关肠道屏障损伤的一个有希望的靶点。
Compelling evidence demonstrates the crucial role of the commensal microbiota in host physiology and the detrimental effects of its perturbations following antibiotic treatment. However, the effects of commensal microbiota on intestinal mucosa antimicrobial molecules have not been elucidated systematically. Here, we investigate the impacts of antibiotic-induced depletion and subsequent restoration of the intestinal microbiota on the murine antimicrobial molecules in intestinal mucosa. Our results demonstrate that depletion of commensal microbiota leads to intestinal mucosa atrophy and reduction of antimicrobial molecules, including lysozyme, regenerating islet-derived protein 3 gamma (RegIIIγ), and cryptdin 5 mRNA, whereas subsequent reconstitution of intestinal microbiota by fecal microbiota transplantation (FMT) rescues mucosa morphology and antimicrobials. Importantly, our study shows that down-regulation of aryl hydrocarbon receptor (AhR), interleukin-22 (IL-22), and phosphorylated Stat3 (p-Stat3) is associated with decreased antimicrobials, which might mediate the antibiotic-associated intestinal mucosa injury. Last, exogenous activation of the AhR/IL-22/Stat3 signaling pathway with the AhR agonist 6-formylindolo(3,2-b)carbazole (Ficz) rescued antimicrobial molecule levels markedly after antibiotic treatment to levels similar to those following reconstitution of intestinal microbiota by FMT. Together, our results demonstrate that the AhR/IL-22/Stat3 signaling pathway is involved in the modulation of intestinal mucosa antimicrobial molecules by commensal microbiota and suggest this pathway as a promising target in the treatment of antibiotic-associated gut barrier damage.
登录
查看更多内容
影响因子：
3.5
作者：
Grover M;Kashyap PC
通讯作者：
Kashyap PC
影响因子：
7.8
作者：
Cella M;Colonna M
通讯作者：
Colonna M
DOI：
10.1073/pnas.0808723105
发表时间：
2008-12-30
影响因子：
11.1
作者：
Vaishnava, Shipra;Behrendt, Cassie L.;Hooper, Lora V.
通讯作者：
Hooper, Lora V.
DOI：
10.1126/science.1221789
发表时间：
2012-06-08
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Iliev ID;Funari VA;Taylor KD;Nguyen Q;Reyes CN;Strom SP;Brown J;Becker CA;Fleshner PR;Dubinsky M;Rotter JI;Wang HL;McGovern DP;Brown GD;Underhill DM
通讯作者：
Underhill DM
影响因子：
7.3
作者：
Ekmekciu I;von Klitzing E;Fiebiger U;Escher U;Neumann C;Bacher P;Scheffold A;Kühl AA;Bereswill S;Heimesaat MM
通讯作者：
Heimesaat MM