Lactobacillus reuteri increases mucus thickness and ameliorates dextran sulphate sodium-induced colitis in mice
Lactobacillus reuteri increases mucus thickness and ameliorates dextran sulphate sodium-induced colitis in mice
复制标题
DOI：
10.1111/apha.12695
复制
发表时间：
2016-08-01
影响因子：
6.3
通讯作者：
Holm, L.
中科院分区：
文献类型：
--
作者：
Ahl, D.;Liu, H.;Holm, L.
目的探讨瑞氏乳杆菌R2LC和ATCC PTA 4659(4659)对小鼠结肠炎的保护作用及其机制。通过临床观察、组织学评价和酶联免疫吸附试验(ELISA)检测结肠组织髓过氧化物酶(MPO)和促炎性细胞因子来评估疾病的严重程度。用微量吸管测量粘液厚度，用免疫组织化学方法检测紧密连接蛋白的表达。结果从临床和组织学两方面评价，路氏乳杆菌R2LC或4659均能显著减轻结肠炎的严重程度。DSS可使炎症标志物MPO、IL-1、IL-6和小鼠角质形成细胞趋化因子(MKC)升高，而路氏乳杆菌株则显著降低。在对照组和DSS处理的小鼠中，DSS显著降低了小鼠的粘液厚度，而路氏乳杆菌显著增加了小鼠的粘液厚度。结论两株不同来源的罗氏乳杆菌对小鼠结肠炎均有保护作用，其中一株来源于人，一株来源于大鼠。这种保护背后的机制至少可以部分解释为粘液厚度的增加以及隐窝干细胞区域的上皮变紧。
AimThe aim of this study was to investigate whether two Lactobacillus reuteri strains (rat-derived R2LC and human-derived ATCC PTA 4659 (4659)) could protect mice against colitis, as well as delineate the mechanisms behind this protection.MethodsMice were given L.reuteri R2LC or 4659 by gavage once daily for 14days, and colitis was induced by addition of 3% DSS (dextran sulphate sodium) to drinking water for the last 7days of this period. The severity of disease was assessed through clinical observations, histological evaluation and ELISA measurements of myeloperoxidase (MPO) and pro-inflammatory cytokines from colonic samples. Mucus thickness was measured invivo with micropipettes, and tight junction protein expression was assessed using immunohistochemistry.ResultsColitis severity was significantly reduced by L.reuteri R2LC or 4659 when evaluated both clinically and histologically. The inflammation markers MPO, IL-1, IL-6 and mKC (mouse keratinocyte chemoattractant) were increased by DSS and significantly reduced by the L.reuteri strains. The firmly adherent mucus thickness was reduced by DSS, but significantly increased by L.reuteri in both control and DSS-treated mice. Expression of the tight junction proteins occludin and ZO-1 was significantly increased in the bottom of the colonic crypts by L.reuteri R2LC.ConclusionThese results demonstrate that each of the two different L. reuteri strains, one human-derived and one-rat-derived, protects against colitis in mice. Mechanisms behind this protection could at least partly be explained by the increased mucus thickness as well as a tightened epithelium in the stem cell area of the crypts.