Elucidation of Mechanism for Preventive and Therapeutic of Koji(Aspergillus orizae NK-Koji)Fermentation Components on Inflammatory Bowel Disease in Terms of Gene Expresssion

目的：克罗恩病（CD）的病因尚不清楚。然而，口服益生菌和合生元可能是有益的，因为肠道内容物和细菌相关的免疫异常被认为是相关的。在CD中，观察到炎性细胞因子如TNF-α、IL-1 β和IL-6的过度产生，并且已经施用生物制剂和免疫抑制剂来抑制或使这种过度产生正常化。在这里，我们研究了预防和治疗炎症性肠病的可能性，口服曲（曲霉菌NK-曲）发酵成分含有益生菌和koji.SUBJECTS和方法：我们收集了10 CD患者的外周血白细胞和基因表达谱芯片的方法进行分析。大约一万个基因被用于分析。克罗恩病活动指数（CDAI）和CRP、红细胞沉降率等分别用于疾病状态和炎症指数，结果：与使用健康对照基因的分析相比，在治疗前有大约40个上调基因和大约50个下调基因。在处理过程中，一些基因的表达发生了变化，大约有50个基因的表达可能与CD活性有关。这些基因包括THF-alpha，IL-1 β，IL-4和IL-12，结果与以前报道的结果相似。结论：口服含有益生菌和曲的曲发酵成分导致CD疾病状态的改善。其机制之一是抑制Th-1细胞因子。通过基因芯片技术检测CD患者炎性细胞因子等基因的表达，有望为CD的诊断和治疗提供新的工具。

PURPOSE : The causes of Crohn's disease (CD) are unknown. However oral administration of probiotics and synbiotics may be beneficial, since intestinal contents-and bacteria-related abnormality of immunity is proposed to be involved. In CD, there was obsereved overproduction of inflammatory cytikine such as TNF-alpha, IL-1 beta and IL-6, and biological preparations and immunosuppressive agents have been administered for restraint or normalization of such overproduction. Here we examined the possibility of prevention and therapy of inflammatory bowel disease by oral administration of koji (Aspergillus orizae NK-Koji) fermentation components containing probiotics and koji.SUBJECTS AND METHODS : We collected the peripheral leucocytes from ten CD patients and analyzed the gene expression using cDNA microarray method. Approximately ten thousands genes were used for the analysis. Crohn' s Disease Activity Index (CDAI) and CRP, erythrocyte sedimentation rate and others were used for disease status and inflammatory index, respectively.RESULTS : There were about 40 up-regulated genes and about 50 down-regulated genes prior to the treatment, compared to the analysis using genes from healthy controls. The expression of some genes was changed during the treatment, and there were about 50 genes whose gene expression might be changed in relation to CD activity. Those genes included THF-alpha, IL-1 beta, IL-4 and IL-12, and the results were similar to those reported previously.CONCLUSIONS : Oral administration of koji fermentation components containing probiotics and koji resulted in the improvement of CD disease status. One of the mechanisms will be suppression of Th-1 cytokines. It is expected to develop novel diagnosis tools and therapies for CD by the analysis of gene expression of inflammatory cytokines and other genes detected by cDNA microarray method.