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Oral administration of Lactobacillus plantarum 299v modulates gene expression in the ileum of pigs: prediction of crosstalk between intestinal immune cells and sub-mucosal adipocytes

机译:口服植物乳杆菌299v调节猪回肠中的基因表达:预测肠道免疫细胞与粘膜下脂肪细胞之间的串扰

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To study host–probiotic interactions in parts of the intestine only accessible in humans by surgery (jejunum, ileum and colon), pigs were used as model for humans. Groups of eight 6-week-old pigs were repeatedly orally administered with 5?×?1012 CFU Lactobacillus plantarum 299v (L. plantarum 299v) or PBS, starting with a single dose followed by three consecutive daily dosings 10?days later. Gene expression was assessed with pooled RNA samples isolated from jejunum, ileum and colon scrapings of the eight pigs per group using Affymetrix porcine microarrays. Comparison of gene expression profiles recorded from L. plantarum 299v-treated pigs with PBS-treated pigs indicated that L. plantarum 299v affected metabolic and immunological processes, particularly in the ileum. A higher expression level of several B cell-specific transcription factors/regulators was observed, suggesting that an influx of B cells from the periphery to the ileum and/or the proliferation of progenitor B cells to IgA-committed plasma cells in the Peyer’s patches of the ileum was stimulated. Genes coding for enzymes that metabolize leukotriene B4, 1,25-dihydroxyvitamin D3 and steroids were regulated in the ileum. Bioinformatics analysis predicted that these metabolites may play a role in the crosstalk between intestinal immune cells and sub-mucosal adipocytes. Together with regulation of genes that repress NFKB- and PPARG-mediated transcription, this crosstalk may contribute to tempering of inflammatory reactions. Furthermore, the enzyme adenosine deaminase, responsible for the breakdown of the anti-inflammatory mediator adenosine, was strongly down-regulated in response to L. plantarum 299v. This suggested that L. plantarum 299v-regulated production of adenosine by immune cells like regulatory T cells may also be a mechanism that tempers inflammation in the ileum, and perhaps also in other parts of the pig’s body.
机译:为了研究只能通过手术(空肠,回肠和结肠)在人体内只能进入人体的肠道部分的宿主-益生菌相互作用,将猪用作人类的模型。每组8只6周龄的猪被重复口服5?×?1012 CFU植物乳杆菌299v(L. plantarum 299v)或PBS,从单剂开始,然后连续10天后连续3次每日给药。使用Affymetrix猪微阵列,从每组八只猪的空肠,回肠和结肠刮下分离的RNA样本中评估基因表达。从植物乳杆菌299v处理的猪与PBS处理的猪记录的基因表达谱比较表明,植物乳杆菌299v影响代谢和免疫过程,特别是在回肠中。观察到较高的几种B细胞特异性转录因子/调节剂的表达水平,这表明在淋巴结的Peyer斑中,B细胞从外周流入回肠和/或祖细胞B细胞增殖到IgA赋予浆细胞。回肠受到刺激。回肠中调控着编码可代谢白三烯B4、1,25-二羟基维生素D3和类固醇的酶的基因。生物信息学分析预测,这些代谢物可能在肠道免疫细胞与粘膜下脂肪细胞之间的串扰中起作用。与抑制NFKB和PPARG介导的转录的基因的调节一起,这种串扰可能有助于炎症反应的缓解。此外,响应于植物乳杆菌299v,负责消炎介质腺苷分解的酶腺苷脱氨酶被强烈下调。这表明植物乳杆菌299v通过调节性T细胞之类的免疫细胞调节腺苷的产生,也可能是缓解回肠甚至猪体其他部位炎症的机制。

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