Gut Microbiota as a Modulator of Paneth Cells During Parenteral Nutrition in Mice
Gut Microbiota as a Modulator of Paneth Cells During Parenteral Nutrition in Mice
复制标题
DOI：
10.1002/jpen.1162
复制
发表时间：
2018-11
影响因子：
3.4
通讯作者：
Jiwei Wang;F. Tian;Peng Wang;Huijun Zheng;Ying Zhang;H. Tian;Li Zhang;Xuejin Gao;Xinying Wang
中科院分区：
文献类型：
--
作者：
Jiwei Wang;F. Tian;Peng Wang;Huijun Zheng;Ying Zhang;H. Tian;Li Zhang;Xuejin Gao;Xinying Wang
背景肠外营养（PN）导致潘氏细胞衍生的抗微生物肽的产生减少，并伴随着肠道的生态失调。肠外营养期间肠道微生物群在调节潘氏细胞功能中的作用尚不清楚。方法雄性C57 BL/6小鼠在饮用水中接受抗生素鸡尾酒（Abx）或不含抗生素（Normal）2周，然后喂食标准实验室食物（Abx-Chow和Normal-Chow）或连续输注PN溶液（Abx-PN和Normal-PN）7天。在一项单独的实验中，通过管饲法将已接受7天饲料或PN的小鼠的肠内容物转移至无菌（GF）小鼠。结果抗生素处理可降低溶菌酶和RegIIIγ的蛋白水平及α-防御素5的mRNA水平，而PN处理对上述蛋白水平无进一步影响。然而，这些测量值在Abx-PN小鼠中高于在Normal-PN小鼠中。与Chow→GF小鼠相比，PN→GF小鼠体重减轻，小肠长度缩短，回肠绒毛严重萎缩，溶菌酶、RegIIIγ蛋白和α-防御素5 mRNA水平降低。回肠中白细胞介素（IL）-22和IL-17 mRNA水平下降。主成分分析显示，Chow和PN以及Chow→GF和PN→GF组的代谢物组成之间存在重大差异，这似乎表明色氨酸代谢异常。结论肠道菌群在PN相关的潘氏细胞功能障碍中起着重要作用。PN期间的菌群失调可能会改变微生物代谢产物的产生，从而影响潘氏细胞衍生的抗菌肽的产生。
BACKGROUND Parenteral nutrition (PN) leads to decreased production of Paneth cell-derived antimicrobial peptides and is accompanied by dysbiosis of the gut. The role of gut microbiota in regulating Paneth cell function during PN is unknown. METHODS Male C57BL/6 mice received either an antibiotic cocktail (Abx) or nothing (Normal) in their drinking water for 2 weeks before being fed either standard laboratory chow (Abx-Chow and Normal-Chow) or a continuous infusion of PN solution (Abx-PN and Normal-PN) for 7 days. In a separate experiment, the intestinal contents of mice having received 7 days of Chow or PN were transferred by gavage to germ-free (GF) mice. RESULTS Antibiotic treatment decreased the protein levels of lysozyme and RegIIIγ and the mRNA level of α-defensin 5, with no further effect by PN compared with chow. However, these measurements were higher in Abx-PN mice than in Normal-PN mice. When compared with Chow→GF, PN→GF mice demonstrated lower body weight, shorter intestinal length, severe atrophy of the ileum villus, and lower levels of lysozyme and RegIIIγ protein and α-defensin 5 mRNA. Interleukin (IL)-22 and IL-17 mRNA levels declined in the ileum. Principal component analysis revealed major differences between the metabolite compositions of the Chow and PN, as well as the Chow→GF and PN→GF groups that appears to indicate aberrant tryptophan metabolism. CONCLUSIONS Gut microbiota plays a vital role in PN-related Paneth cell dysfunction. Dysbiosis during PN might alter the production of microbial metabolites, thereby influencing the production of Paneth cell-derived antimicrobial peptides.