E Durans Strain M4-5 Isolated From Human Colonic Flora Attenuates Intestinal Inflammation
E Durans Strain M4-5 Isolated From Human Colonic Flora Attenuates Intestinal Inflammation
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DOI：
10.1007/dcr.0b013e3181f4b148
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发表时间：
2010-12-01
影响因子：
3.9
通讯作者：
Schwartz, Betty
中科院分区：
文献类型：
--
作者：
Avram-Hananel, Liraz;Stock, Julia;Schwartz, Betty
目得：本研究的目的是评价从人类结肠植物群中分离的一种独特的高产丁酸盐的细菌菌株--坚固肠球菌（Enterococcus durans）在预防和治疗肠道炎症中的体外和体内作用。采用区室化Caco-2/白细胞共培养模型，检测了E durans及其代谢产物丁酸盐对基础和大肠杆菌刺激的促炎免疫因子分泌的体外影响（IL-8、IL-6和TNF-α）和抗炎细胞因子IL-10。阿葡聚糖硫酸钠诱导的结肠炎的小鼠模型被用来检查在体内的预防和治疗与E durans的临床，生化和组织学参数的inflammation.RESULTS：在共培养模型中，治疗与E durans和丁酸盐减少的基础，以及大肠杆菌刺激分泌IL-8，IL-6，和TNF-α和IL-10的分泌增加。在体内小鼠模型中，预防性给予硬肠球菌显著改善了临床疾病活动指数（体重减轻、粪便出血和粪便稠度），降低了结肠组织提取物中的髓过氧化物酶浓度，改善了结肠炎症的组织学评分，并抑制了促炎免疫因子的结肠转录。单独治疗对这些参数的影响更为温和，但仍然显着。我们得出结论，E durans菌株M4至5及其代谢产物丁酸盐诱导显著的抗炎作用，通过调节促炎和抗炎免疫因子以及保护肠上皮完整性介导，这表明这种新的抗炎细菌可能是避免炎性肠病的优选有用的预防性治疗。
PURPOSE: The aim of this study was to evaluate in vitro and in vivo effects of a unique high-butyrate-producing bacterial strain from human colonic flora, Enterococcus durans, in prevention and treatment of intestinal inflammation.METHODS: A compartmentalized Caco-2/leukocyte coculture model was used to examine the in vitro effects of E durans and its metabolite butyrate on basal and Escherichia coli-stimulated secretion of proinflammatory immune factors (IL-8, IL-6, and TNF-alpha) and the anti-inflammatory cytokine IL-10. A murine model of dextran sodium sulfate-induced colitis was used to examine in vivo effects of prevention and therapy with E durans on clinical, biochemical, and histologic parameters of inflammation.RESULTS: In the coculture model, treatment with E durans and with butyrate reduced basal as well as E coli stimulated secretion of IL-8, IL-6, and TNF-alpha and increased secretion of IL-10. In the in vivo murine model, preventive administration of E durans significantly ameliorated clinical disease activity index (weight loss, fecal bleeding, and stool consistency), reduced myeloperoxidase concentration in colon tissue extracts, improved histologic scores of colonic inflammation, and inhibited colonic transcription of proinflammatory immune factors. The effect of therapeutic treatment alone on these parameters was more moderate but still significant.CONCLUSIONS: We conclude that E durans strain M4 to 5 and its metabolic product butyrate induce significant anti-inflammatory effects, mediated by regulation of pro- and anti-inflammatory immune factors as well as preservation of intestine epithelial integrity, suggesting that this novel anti-inflammatory bacterium may be preferentially a useful prophylactic treatment to avoid inflammatory bowel disease.