Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China.
J Dig Dis. 2013 Oct;14(10):526-35. doi: 10.1111/1751-2980.12079.
This study aimed to analyze the effects of 5-aminosalicylic acid (5-ASA) on intestinal microbiota and immune regulation in inflammatory bowel disease (IBD) and to investigate the correlation between intestinal microbiota and immune factors.
Colitis in mice was induced by oxazolone. The community composition of luminal and mucosal microbiota was analyzed by a terminal restriction fragment length polymorphism. The expression of occludin, toll-like receptor (TLR)-2, TLR-4 and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) p65 proteins were measured by immunohistochemistry and Western blot. Linear correlation between intestinal microbial community and the severity of the colitis or intestinal microbial community and expressions of immune factors were determined.
Protective bacteria decreased while aggressive bacteria increased in the colitis group. The richness and diversity of both luminal and mucosal microbiota decreased in the colitis group the decrease was enhanced in the 5-ASA-treated group. The diversity of mucosal microbiota significantly correlated with the extent of the colitis. Expressions of occludin, TLR-2, TLR-4, tumor necrosis factor-α and NF-κB p65 were significantly correlated with the diversity of mucosal microbiota.
Mucosal microbiota are important in the pathogenesis of IBD. 5-ASA increases protective bacteria but decreases aggressive bacteria, thus inducing the new intestinal microbial homeostasis.
本研究旨在分析 5-氨基水杨酸(5-ASA)对炎症性肠病(IBD)中肠道微生物群和免疫调节的影响,并探讨肠道微生物群与免疫因子之间的相关性。
通过氧化偶氮甲烷诱导小鼠结肠炎。通过末端限制性片段长度多态性分析腔和黏膜微生物群落的组成。通过免疫组织化学和 Western blot 测定紧密连接蛋白、 toll 样受体(TLR)-2、TLR-4 和核因子 kappa-轻链增强子的活化 B 细胞(NF-κB)p65 蛋白的表达。通过线性相关性分析确定肠道微生物群落与结肠炎严重程度之间的关系以及肠道微生物群落与免疫因子表达之间的关系。
结肠炎组中保护性细菌减少而侵袭性细菌增加。结肠炎组中腔和黏膜微生物群落的丰富度和多样性降低,而 5-ASA 治疗组的降低更为明显。黏膜微生物群落的多样性与结肠炎的严重程度显著相关。紧密连接蛋白、TLR-2、TLR-4、肿瘤坏死因子-α和 NF-κB p65 的表达与黏膜微生物群落的多样性显著相关。
黏膜微生物群在 IBD 的发病机制中起重要作用。5-ASA 增加保护性细菌而减少侵袭性细菌,从而诱导新的肠道微生物群稳态。