Parenteral Nutrition Decreases Paneth Cell Function and Intestinal Bactericidal Activity While Increasing Susceptibility to Bacterial Enteroinvasion
Parenteral Nutrition Decreases Paneth Cell Function and Intestinal Bactericidal Activity While Increasing Susceptibility to Bacterial Enteroinvasion
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DOI：
10.1177/0148607113497514
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发表时间：
2014-09-01
影响因子：
3.4
通讯作者：
Kudsk, Kenneth A.
中科院分区：
文献类型：
--
作者：
Heneghan, Aaron F.;Pierre, Joseph F.;Kudsk, Kenneth A.
引言：肠外营养（PN）增加了禁忌肠内喂养患者的感染风险。潘氏细胞产生并分泌保护粘膜免受病原体侵害的抗菌产物。它们的损失与宿主-病原体相互作用增加、粘膜炎症和微生物组组成改变有关。假设：我们假设PN降低了潘氏细胞产物表达，这些变化将降低胆碱能刺激后组织分泌物的杀菌特性，增加肠粘膜侵袭，并改变肠道微生物组。方法：实验1：雄性ICR小鼠随机分为两组：普通饲料组（n = 8）和肠外营养组（n = 8）。收集回肠组织，使用RT-PCR进行潘氏细胞抗微生物表达，用胆碱能激动剂刺激潘氏细胞杀菌活性，或用于评估EVISC中的细菌肠侵袭。实验2：将小鼠随机分配至饲料（n = 11）或PN（n = 8），并收集回肠洗涤物用于16 s焦磷酸测序分析。结果：与普通饲料相比，PN降低了REGIII-g（p < 0.002）、溶菌酶（p < 0.002）和cryptdin-4（p < 0.03）的组织表达。在门的水平上，PN减少了厚壁菌门的总数，但增加了拟杆菌门和变形菌门的总数。在功能上，PN组织分泌物的杀菌性较低（p < 0.03），并表现出对大肠杆菌肠侵袭的易感性增加（p < 0.02）。结论：非肠内营养的肠外营养可损害肠粘膜固有免疫功能。潘氏细胞抗微生物蛋白的组织表达降低与微生物组的组成变化、粘膜分泌物的杀菌活性降低以及对大肠杆菌肠侵袭的更大易感性相关。这些变化可以部分解释肠外喂养患者感染风险增加的原因。
Introduction: Parenteral nutrition (PN) increases the risk of infection in patients with contraindication to enteral feeding. Paneth cells produce and secrete antimicrobial products that protect the mucosa from pathogens. Their loss is associated with increased host-pathogen interactions, mucosal inflammation, and altered microbiome composition. Hypothesis: We hypothesized that PN reduces Paneth cell product expression, and these changes would reduce bactericidal properties of tissue secretions following cholinergic stimulation, increase mucosal enteroinvasion, and shift the intestinal microbiome. Method: Experiment 1: Male ICR mice were randomized to Chow (n = 8) or PN (n = 8). Ileum tissue was collected for Paneth cell antimicrobial expression using RT-PCR, stimulated with a cholinergic agonist degranulate Paneth cells bactericidal activity, or used to assess bacterial enteroinvasion in EVISC. Experiment 2: Mice were randomized to Chow (n = 11) or PN (n = 8) and ileum washing was collected for 16s pyrosequencing analysis. Results: Compared to Chow, PN decreased tissue expression of REGIII-g (p < 0.002), lysozyme (p < 0.002), and cryptdin-4 (p < 0.03). At the phylum level, PN decreased total Firmicutes but increased total Bacteroidetes, and Proteobacteria. Functionally, secretions from PN tissue was less bactericidal (p < 0.03) and demonstrated increased susceptibility to enteroinvasion by E coli (p < 0.02). Conclusion: PN without enteral nutrition impairs innate mucosal immune function. Tissue expression of Paneth cell antimicrobial proteins decreases associated with compositional shifts to the microbiome, decreased bactericidal activity of mucosal secretions and greater susceptibility of to enteroinvasion by E coli. These changes may explain in-part the increased risk of infection in parenterally fed patients.