Specific microbiome changes in a mouse model of parenteral nutrition associated liver injury and intestinal inflammation.
Specific microbiome changes in a mouse model of parenteral nutrition associated liver injury and intestinal inflammation.
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DOI：
10.1371/journal.pone.0110396
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Sokol RJ
中科院分区：
文献类型：
--
作者：
Harris JK;El Kasmi KC;Anderson AL;Devereaux MW;Fillon SA;Robertson CE;Wagner BD;Stevens MJ;Pace NR;Sokol RJ
肠外营养（PN）一直是对肠内喂养不耐受的婴儿的救命治疗。然而，在相当数量的PN依赖婴儿中，PN与肝损伤（PN相关肝损伤：PNALI）相关。我们以前曾报道过一种新的PNALI小鼠模型，其中PN输注结合肠损伤导致肝损伤。在该模型中，脂多糖激活Toll样受体4信号传导、大豆油衍生的植物甾醇和库普弗细胞（KCs）的促炎激活发挥了关键作用。本研究的目的是探索与PNALI相关的肠道微生物组的变化。PNALI小鼠中的微生物组分析鉴定了与PNALI相关的结肠微生物群内的特定改变，以及这些群落与PN溶液的脂质组成的进一步关联。肠道炎症或单独使用基于豆油的PN输注（在没有肠内喂养的情况下）导致肠道微生物群发生变化。然而，该组合导致PNALI小鼠中特定分类群丹毒丝菌科的积累（23.8%对盐水输注对照中的1.7%）。此外，肠内抗生素治疗显著减弱了PNALI，这也与丹毒丝菌科（0.6%）和革兰氏阴性成分（拟杆菌属的S24-7谱系）（PNALI中53.5%对0.8%）的显著减少相关。重要的是，从PN溶液中去除基于豆油的脂肪乳剂导致丹毒丝菌科的显著减少以及PNALI的减弱。最后，除了大豆衍生的植物甾醇（豆甾醇），鱼油为基础的PN恢复丹毒丰富和PNALI。大豆油衍生的植物甾醇和结肠微生物群中相关的特定细菌群与PNALI相关。来自这些细菌的产物可直接触发KCs的活化并促进PNALI。此外，结果表明，PN溶液的脂质修饰可能会改变与PNALI相关的特定肠道细菌种类，从而提出了PNALI管理策略。
Parenteral nutrition (PN) has been a life-saving treatment in infants intolerant of enteral feedings. However, PN is associated with liver injury (PN Associated Liver Injury: PNALI) in a significant number of PN-dependent infants. We have previously reported a novel PNALI mouse model in which PN infusion combined with intestinal injury results in liver injury. In this model, lipopolysaccharide activation of toll-like receptor 4 signaling, soy oil-derived plant sterols, and pro-inflammatory activation of Kupffer cells (KCs) played key roles. The objective of this study was to explore changes in the intestinal microbiome associated with PNALI. Microbiome analysis in the PNALI mouse identified specific alterations within colonic microbiota associated with PNALI and further association of these communities with the lipid composition of the PN solution. Intestinal inflammation or soy oil-based PN infusion alone (in the absence of enteral feeds) caused shifts within the gut microbiota. However, the combination resulted in accumulation of a specific taxon, Erysipelotrichaceae (23.8% vs. 1.7% in saline infused controls), in PNALI mice. Moreover, PNALI was markedly attenuated by enteral antibiotic treatment, which also was associated with significant reduction of Erysipelotrichaceae (0.6%) and a Gram-negative constituent, the S24-7 lineage of Bacteroidetes (53.5% in PNALI vs. 0.8%). Importantly, removal of soy oil based-lipid emulsion from the PN solution resulted in significant reduction of Erysipelotrichaceae as well as attenuation of PNALI. Finally, addition of soy-derived plant sterol (stigmasterol) to fish oil-based PN restored Erysipelotrichaceae abundance and PNALI. Soy oil-derived plant sterols and the associated specific bacterial groups in the colonic microbiota are associated with PNALI. Products from these bacteria may directly trigger activation of KCs and promote PNALI. Furthermore, the results indicate that lipid modification of PN solutions may alter specific intestinal bacterial species associated with PNALI, and thus suggest strategies for management of PNALI.
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影响因子：
3.4
作者：
Buchman, A
通讯作者：
Buchman, A
影响因子：
25.7
作者：
Fouts, Derrick E.;Torralba, Manolito;Nelson, Karen E.;Brenner, David A.;Schnabl, Bernd
通讯作者：
Schnabl, Bernd
影响因子：
17.1
作者：
El Kasmi KC;Anderson AL;Devereaux MW;Vue PM;Zhang W;Setchell KD;Karpen SJ;Sokol RJ
通讯作者：
Sokol RJ
DOI：
10.1002/hep.25500
发表时间：
2012-05
期刊：
Hepatology (Baltimore, Md.)
影响因子：
--
作者：
El Kasmi KC;Anderson AL;Devereaux MW;Fillon SA;Harris JK;Lovell MA;Finegold MJ;Sokol RJ
通讯作者：
Sokol RJ
影响因子：
4.4
作者：
Harris, J. Kirk;Sahl, Jason W.;Spear, John R.
通讯作者：
Spear, John R.