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多发酵芽孢杆菌通过促进结肠炎小鼠的细胞保护作用来改善结肠炎症。

Bacillus polyfermenticus ameliorates colonic inflammation by promoting cytoprotective effects in colitic mice.

作者信息

Im Eunok, Choi Yoon Jeong, Pothoulakis Charalabos, Rhee Sang Hoon

机构信息

Division of Digestive Diseases, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA.

出版信息

J Nutr. 2009 Oct;139(10):1848-54. doi: 10.3945/jn.109.108613. Epub 2009 Aug 12.

Abstract

Although human consumption of Bacillus polyfermenticus provides several health benefits, the probiotic effect of this bacterium against colonic inflammation has not yet, to our knowledge, been studied. Therefore, we induced colitis in mice by oral or intrarectal administration of dextran sodium sulfate (DSS) or trinitrobenzenosulfonic acid (TNBS), respectively, and investigated the effect of B. polyfermenticus on colitis. We found that mice treated with DSS or TNBS along with B. polyfermenticus had reduced mortality and severity of colitis (weight loss, diarrhea, and mucosal damages) than mice treated with DSS or TNBS alone. B. polyfermenticus also reduced the expression of inflammatory molecules, including chemokine (C-X-C motif) ligand 1, intercellular adhesion molecule, and tumor necrosis factor-alpha, but enhanced the expression of the antiinflammatory cytokine interleukin-10 in the inflamed mouse colon. Moreover, B. polyfermenticus suppressed apoptosis both in vivo in inflamed colonic mucosa and in vitro in colonic epithelial cells stimulated with apoptosis-inducing agents (FasL or Clostridium difficile Toxin A) when the apoptotic response was determined by a terminal deoxynucleotidyl transferase dUTP nick end labeling assay and cleavage of poly(ADP-ribose) polymerase or caspase-3, respectively. Treating colonic epithelial cells with B. polyfermenticus-conditioned medium (BPCM) enhanced cell proliferation and induced the phosphoinositide 3-kinases/Akt signaling pathway, suggesting that this bacterium can promote epithelial cell proliferation. BPCM also promoted the migration of colonic epithelial cells. These data suggest that B. polyfermenticus ameliorates colonic inflammation by suppressing apoptosis and promoting epithelial cell proliferation and migration.

摘要

尽管人类食用多发酵芽孢杆菌对健康有诸多益处,但据我们所知,这种细菌对结肠炎症的益生菌作用尚未得到研究。因此,我们分别通过口服或直肠内给予葡聚糖硫酸钠(DSS)或三硝基苯磺酸(TNBS)诱导小鼠结肠炎,并研究了多发酵芽孢杆菌对结肠炎的影响。我们发现,与单独用DSS或TNBS处理的小鼠相比,用DSS或TNBS联合多发酵芽孢杆菌处理的小鼠死亡率降低,结肠炎严重程度(体重减轻、腹泻和黏膜损伤)减轻。多发酵芽孢杆菌还降低了炎症分子的表达,包括趋化因子(C-X-C基序)配体1、细胞间黏附分子和肿瘤坏死因子-α,但增强了炎症小鼠结肠中抗炎细胞因子白细胞介素-10的表达。此外,当通过末端脱氧核苷酸转移酶dUTP缺口末端标记测定法以及分别通过聚(ADP-核糖)聚合酶或半胱天冬酶-3的裂解来确定凋亡反应时,多发酵芽孢杆菌在体内炎症结肠黏膜和体外受凋亡诱导剂(FasL或艰难梭菌毒素A)刺激的结肠上皮细胞中均抑制了凋亡。用多发酵芽孢杆菌条件培养基(BPCM)处理结肠上皮细胞可增强细胞增殖并诱导磷酸肌醇3-激酶/蛋白激酶B信号通路,这表明这种细菌可以促进上皮细胞增殖。BPCM还促进了结肠上皮细胞的迁移。这些数据表明,多发酵芽孢杆菌通过抑制凋亡以及促进上皮细胞增殖和迁移来改善结肠炎症。

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