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，口服益生菌和合生菌可能是有益的，因为肠道内容物和细菌相关的免疫异常被认为涉及。在CD中，观察到炎性细胞因子如TNF-α、IL-1β和IL-6的过度产生，并应用生物制剂和免疫抑制剂来抑制或正常化这种过度产生。在这里，我们探讨了口服含有益生菌和曲剂的发酵曲(Aspergillusorizae NK-Koji)预防和治疗炎症性肠病的可能性。材料和方法：收集10例CD患者外周血白细胞，用基因芯片技术分析其基因表达。大约有一万个基因被用于分析。用克罗恩S疾病活动性指数、C反应蛋白、血沉等指标评价病情和炎症指标。结果：与正常对照组比较，治疗前上调基因约40个，下调基因约50个。在处理过程中，一些基因的表达发生了变化，其中约有50个基因的表达可能与镉的活性有关。这些基因包括THF-α、IL-1β、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剂的曲发酵成分可以改善CD的病情。机制之一将是抑制Th-1细胞因子。应用基因芯片技术分析炎症细胞因子等基因的表达，可望为CD的诊断和治疗提供新的手段和方法。

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.