Reduction of colitis by prebiotics in HLA-1327 transgenic rats is associated with microflora changes and immunomodulation
Reduction of colitis by prebiotics in HLA-1327 transgenic rats is associated with microflora changes and immunomodulation
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DOI：
10.1097/01.mib.0000183421.02316.d5
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发表时间：
2005-11-01
影响因子：
4.9
通讯作者：
Dieleman, LA
中科院分区：
文献类型：
--
作者：
Hoentjen, F;Welling, GW;Dieleman, LA
HLA-B27 转基因大鼠在特定的无病原体条件 (SPF) 下会出现自发性结肠炎，但无菌大鼠仍然没有疾病，这强调了肠道细菌在慢性肠道炎症发病机制中的作用。益生元是通过刺激潜在健康促进细菌的生长和/或活性来影响宿主的膳食物质。本研究的目的是探讨益生元是否可以预防 SPF HLA-B27 大鼠的结肠炎，其次探讨其保护机制。 SPF HLA-B27 转基因大鼠在出现临床可检测的结肠炎之前口服或不口服益生元组合长链菊粉和低聚果糖（协同 1）。七周后，收集盲肠和结肠组织进行盲肠总评分（GCS）、组织学炎症评分（0-4 级）和粘膜细胞因子测量。收集盲肠和结肠内容物，通过 PCR 变性梯度凝胶电泳 (PCR-DGGE) 和荧光原位杂交 (FISH) 分析肠道微生物群，并分析短链脂肪酸组成。益生元治疗显着降低了盲肠和结肠的 GCS 和炎症组织学评分。益生元治疗还降低了盲肠IL-1β，但增加了盲肠TGF-β浓度。菊粉/低聚果糖改变了盲肠和结肠 PCR-DGGE 谱，FISH 分析显示，与水处理的大鼠相比，益生元治疗后盲肠乳酸杆菌和双歧杆菌数量显着增加。总之，益生元组合 Synergy I 可减轻 HLA-B27 转基因大鼠的结肠炎，其效果与肠道微生物群的改变、组织促炎细胞因子的减少和免疫调节分子的增加有关。这些结果表明益生元有望作为慢性炎症性肠病的主要或辅助维持疗法。
HLA-B27 transgenic rats develop spontaneous colitis under specific pathogen-free conditions (SPF) but germ-free rats remain disease-free, emphasizing a role for intestinal bacteria in the pathogenesis of chronic intestinal inflammation. Prebiotics are dietary substances that affect the host by stimulating growth and/or activity of potentially health promoting bacteria. The aims of this study were to investigate whether prebiotics can prevent colitis in SPF HLA-B27 rats, and secondly, to explore mechanisms of protection. SPF HLA-B27 transgenic rats received orally the prebiotic combination long-chain inulin and oligofructose (Synergy 1), or not, prior to the development of clinically detectable colitis. After seven weeks, cecal and colonic tissues were collected for gross cecal scores (GCS), histologic inflammatory scores (scale 0-4), and mucosal cytokine measurement. Cecal and colonic contents were collected for analysis of the gut rnicrobiota by PCR-denaturing gradient gel electrophoresis (PCR-DGGE) and fluorescent in-situ hybridization (FISH), and analysis of short-chain fatty acid composition. Prebiotic treatment significantly decreased GCS and inflammatory histologic scores in the cecum and colon. Prebiotic treatment also decreased cecal IL-I beta, but increased cecal TGF-beta concentrations. Inulin/oligofructose altered the cecal and colonic PCR-DGGE profiles, and FISH analysis showed significant increases in cecal Lactobacillus and Bifidobacterium populations after prebiotic treatment compared with water-treated rats. In conclusion, the prebiotic combination Synergy I reduced colitis in HLA-B27 transgenic rats, which effect was associated with alterations to the gut microbiota, decreased tissue proinflammatory cytokines and increased immunomodulatory molecules. These results show promise for prebiotics as primary or adjuvant maintenance therapy for chronic inflammatory bowel diseases.