Intestinal Osteopontin Protects From Alcohol-induced Liver Injury by Preserving the Gut Microbiome and the Intestinal Barrier Function.
Intestinal Osteopontin Protects From Alcohol-induced Liver Injury by Preserving the Gut Microbiome and the Intestinal Barrier Function.
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DOI：
10.1016/j.jcmgh.2022.06.012
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发表时间：
2022
影响因子：
7.2
通讯作者：
Nieto, Natalia
中科院分区：
文献类型：
--
作者：
Das, Sukanta;Song, Zhuolun;Han, Hui;Ge, Xiaodong;Desert, Romain;Athavale, Dipti;Komakula, Sai Santosh Babu;Magdaleno, Fernando;Chen, Wei;Lantvit, Daniel;Guzman, Grace;Nieto, Natalia
肠肝轴在酒精性肝病(ALD)的发病机制中起着关键作用。我们证明OPN-/-比野生型(WT)小鼠的ALD更严重；然而，肠道骨桥蛋白(OPN)在ALD中的作用仍不清楚。我们推测，在肠上皮细胞(IECS)中过表达OPN可以通过保护肠道微生物群和肠道屏障功能来改善ALD。OpnΔIEC、OPN Lieber IEC和WT小鼠分别饲喂对照组或乙醇饲料6周。OpnKI IEC而不是opnΔIEC小鼠表现出改善的肠屏障功能和对ALD的保护作用。与WT小鼠相比，酒精喂养的OpnKI IEC的致病细菌更少，有益细菌更多。从OpnKI IEC到WT小鼠的粪便微生物组移植(FMT)对ALD具有保护作用。从乙醇喂养的WT到OpnKI IEC小鼠的FMT未能诱导ALD。空肠IEC中抗菌肽、IL33、pSTAT3、芳香烃受体(AhR)和紧密连接蛋白的表达均高于WT小鼠。与WT小鼠相比，乙醇喂养的OpnKI IEC在门静脉血清中显示更多的色氨酸代谢物和短链脂肪酸。从OpnKI IEC到WT小鼠的FMT增强了IECS AhR和紧密连接蛋白的表达。口服牛奶OPN可复制OpnKI IEC小鼠对ALD的保护作用。在IECS中过表达OPN或给予牛奶OPN可通过肠道抗菌肽维持肠道微生物群。IECS中色氨酸代谢物和短链脂肪酸通过AhR信号的增加，保护了肠屏障功能，保护了ALD。
The gut-liver axis plays a key role in the pathogenesis of alcohol-associated liver disease (ALD). We demonstrated that Opn-/- develop worse ALD than wild-type (WT) mice; however, the role of intestinal osteopontin (OPN) in ALD remains unknown. We hypothesized that overexpression of OPN in intestinal epithelial cells (IECs) could ameliorate ALD by preserving the gut microbiome and the intestinal barrier function. OpnKI IEC, OpnΔIEC, and WT mice were fed control or ethanol Lieber-DeCarli diet for 6 weeks. OpnKI IEC but not OpnΔIEC mice showed improved intestinal barrier function and protection from ALD. There were less pathogenic and more beneficial bacteria in ethanol-fed OpnKI IEC than in WT mice. Fecal microbiome transplant (FMT) from OpnKI IEC to WT mice protected from ALD. FMT from ethanol-fed WT to OpnKI IEC mice failed to induce ALD. Antimicrobial peptides, Il33, pSTAT3, aryl hydrocarbon receptor (Ahr), and tight-junction protein expression were higher in IECs from jejunum of ethanol-fed OpnKI IEC than of WT mice. Ethanol-fed OpnKI IEC showed more tryptophan metabolites and short-chain fatty acids in portal serum than WT mice. FMT from OpnKI IEC to WT mice enhanced IECs Ahr and tight-junction protein expression. Oral administration of milk OPN replicated the protective effect of OpnKI IEC mice in ALD. Overexpression of OPN in IECs or administration of milk OPN maintain the intestinal microbiome by intestinal antimicrobial peptides. The increase in tryptophan metabolites and short-chain fatty acids signaling through the Ahr in IECs, preserve the intestinal barrier function and protect from ALD.
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DOI：
10.1002/hep.30093
发表时间：
2018-12
期刊：
Hepatology (Baltimore, Md.)
影响因子：
--
作者：
Ge X;Arriazu E;Magdaleno F;Antoine DJ;Dela Cruz R;Theise N;Nieto N
通讯作者：
Nieto N
影响因子：
2.9
作者：
Chang SC;Shen MH;Liu CY;Pu CM;Hu JM;Huang CJ
通讯作者：
Huang CJ
DOI：
10.1038/ismej.2012.8
发表时间：
2012-08
期刊：
The ISME journal
影响因子：
--
作者：
通讯作者：
--
影响因子：
13.5
作者：
Ge, Xiaodong;Leung, Tung-Ming;Arriazu, Elena;Lu, Yongke;Urtasun, Raquel;Christensen, Brian;Fiel, Maria Isabel;Mochida, Satoshi;Sorensen, Esben S.;Nieto, Natalia
通讯作者：
Nieto, Natalia
DOI：
10.1152/ajpgi.00014.2013
发表时间：
2013-05-01
影响因子：
4.5
作者：
Ge, Xiaodong;Lu, Yongke;Nieto, Natalia
通讯作者：
Nieto, Natalia