No Gut No Gain! Enteral Bile Acid Treatment Preserves Gut Growth but Not Parenteral Nutrition-Associated Liver Injury in a Novel Extensive Short Bowel Animal Model.
No Gut No Gain! Enteral Bile Acid Treatment Preserves Gut Growth but Not Parenteral Nutrition-Associated Liver Injury in a Novel Extensive Short Bowel Animal Model.
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DOI：
10.1002/jpen.1167
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发表时间：
2018-11
期刊：
影响因子：
--
通讯作者：
Kumar Jain A
中科院分区：
文献类型：
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作者：
Villalona G;Price A;Blomenkamp K;Manithody C;Saxena S;Ratchford T;Westrich M;Kakarla V;Pochampally S;Phillips W;Heafner N;Korremla N;Greenspon J;Guzman MA;Kumar Jain A
肠外营养（PN）通过静脉提供营养;然而，这种挽救生命的治疗与严重的肝脏疾病有关。最近的证据表明，在用肠内胆汁酸（BA）、鹅去氧胆酸（CDCA）和肠道法尼醇X受体（FXR）激动剂治疗的具有完整肠道的动物中，PN相关损伤得到改善，这驱动了肠道-肝脏串扰（GLCT）。我们假设，类似的改善可以在短肠综合征（SBS）的动物。使用仔猪，我们开发了一种新的90%肠切除SBS模型。15头接受PN的SBS仔猪给予CDCA或对照（溶媒对照）2周。安乐死后分析组织和血清。CDCA增加肠道FXR（定量聚合酶链反应; P = 0.008），但不增加下游FXR靶点。肠成纤维细胞生长因子19（FGF 19; P = 0.28）或肝脏FXR（P = 0.75）、FGF 19（P = 0.86）、FGFR 4（P = 0.53）或胆固醇7 α-羟化酶（P = 0.61）无差异。PN导致胆汁淤积;然而，CDCA未观察到改善。肝纤维化或Ki 67、CD 3或细胞角蛋白7的免疫染色与CDCA无差异。PN导致肠道萎缩。CDCA保留（P = 0.04 vs对照）肠道质量和绒毛/隐窝比。对照组肠道质量的中位数（四分位距）为0.28（0.17-0.34），CDCA为0.33（0.26-0.46）。我们注意到，与具有完整肠道的动物不同，在SBS动物模型中，CDCA诱导的肠道源性信号传导的激活不足以引起肝脏改善。因此，似乎GLCT的激活严重依赖于足够肠道的存在。这具有临床相关性，因为它表明BA治疗可能对SBS患者无效。
Parenteral nutrition (PN) provides nutrition intravenously; however, this life-saving therapy is associated with significant liver disease. Recent evidence indicates improvement in PN-associated injury in animals with intact gut treated with enteral bile acid (BA), chenodeoxycholic acid (CDCA), and a gut farnesoid X receptor (FXR) agonist, which drives the gut–liver cross talk (GLCT). We hypothesized that similar improvement could be translated in animals with short bowel syndrome (SBS). Using piglets, we developed a novel 90% gut-resected SBS model. Fifteen SBS piglets receiving PN were given CDCA or control (vehicle control) for 2 weeks. Tissue and serum were analyzed posteuthanasia. CDCA increased gut FXR (quantitative polymerase chain reaction; P = .008), but not downstream FXR targets. No difference in gut fibroblast growth factor 19 (FGF19; P = .28) or hepatic FXR (P = .75), FGF19 (P = .86), FGFR4 (P = .53), or Cholesterol 7 α-hydroxylase (P = .61) was noted. PN resulted in cholestasis; however, no improvement was noted with CDCA. Hepatic fibrosis or immunostaining for Ki67, CD3, or Cytokeratin 7 was not different with CDCA. PN resulted in gut atrophy. CDCA preserved (P = .04 vs control) gut mass and villous/crypt ratio. The median (interquartile range) for gut mass for control was 0.28 (0.17–0.34) and for CDCA was 0.33 (0.26–0.46). We note that, unlike in animals with intact gut, in an SBS animal model there is inadequate CDCA-induced activation of gut-derived signaling to cause liver improvement. Thus, it appears that activation of GLCT is critically dependent on the presence of adequate gut. This is clinically relevant because it suggests that BA therapy may not be as effective for patients with SBS.
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影响因子：
3.7
作者：
Cipriani S;Mencarelli A;Chini MG;Distrutti E;Renga B;Bifulco G;Baldelli F;Donini A;Fiorucci S
通讯作者：
Fiorucci S
DOI：
10.4103/1319-3767.141688
发表时间：
2014-09
期刊：
Saudi journal of gastroenterology : official journal of the Saudi Gastroenterology Association
影响因子：
--
作者：
Alkharfy TM;Ba-Abbad R;Hadi A;Sobaih BH;AlFaleh KM
通讯作者：
AlFaleh KM
影响因子：
16.2
作者：
Gerhard GS;Styer AM;Wood GC;Roesch SL;Petrick AT;Gabrielsen J;Strodel WE;Still CD;Argyropoulos G
通讯作者：
Argyropoulos G
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
3.3
作者：
Burrin D;Stoll B;Moore D
通讯作者：
Moore D