Heneghan Aaron F, Pierre Joseph F, Tandee Kanokwan, Shanmuganayagam Dhanansayan, Wang Xinying, Reed Jess D, Steele James L, Kudsk Kenneth A
Surgical Service of the William S. Middleton Veteran Memorial Hospital, Madison WI, USA.
Department of Surgery, University of Wisconsin-Madison, Madison, WI, USA.
JPEN J Parenter Enteral Nutr. 2014 Sep;38(7):817-824. doi: 10.1177/0148607113497514. Epub 2013 Jul 26.
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.
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.
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.
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).
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.
肠外营养（PN）会增加肠内营养禁忌患者的感染风险。潘氏细胞产生并分泌抗菌产物，保护黏膜免受病原体侵害。其缺失与宿主-病原体相互作用增加、黏膜炎症及微生物群组成改变有关。
我们假设PN会降低潘氏细胞产物表达，这些变化会降低胆碱能刺激后组织分泌物的杀菌特性，增加黏膜肠侵袭，并改变肠道微生物群。
实验1：雄性ICR小鼠随机分为正常饮食组（n = 8）或PN组（n = 8）。收集回肠组织，用逆转录聚合酶链反应（RT-PCR）检测潘氏细胞抗菌表达，用胆碱能激动剂刺激使潘氏细胞脱颗粒以检测杀菌活性，或用于评估在体外侵袭性小肠结肠炎模型（EVISC）中的细菌肠侵袭情况。实验2：小鼠随机分为正常饮食组（n = 11）或PN组（n = 8），收集回肠冲洗液进行16S焦磷酸测序分析。
与正常饮食组相比，PN降低了再生胰岛衍生蛋白3γ（REGIII-g）（p < 0.002）、溶菌酶（p < 0.002）和隐窝抗菌肽-4（p < 0.03）的组织表达。在门水平上，PN降低了厚壁菌门的总量，但增加了拟杆菌门和变形菌门的总量。在功能上，PN组织的分泌物杀菌能力较弱（p < 0.03），并且对大肠杆菌的肠侵袭敏感性增加（p < 0.02）。
无肠内营养的PN会损害先天性黏膜免疫功能。潘氏细胞抗菌蛋白的组织表达降低，与微生物群组成变化、黏膜分泌物杀菌活性降低以及对大肠杆菌肠侵袭的易感性增加有关。这些变化可能部分解释了接受肠外营养患者感染风险增加的原因。
