Centre of Microbial and Plant Genetics, University Hospital, K. U. Leuven, Belgium.
Clin Exp Immunol. 2010 Nov;162(2):306-14. doi: 10.1111/j.1365-2249.2010.04228.x. Epub 2010 Aug 20.
While some probiotic strains might have adjuvant effects in the therapy for inflammatory bowel diseases (IBD), these effects remain controversial and cannot be generalized. In this study, a dltD mutant of the model probiotic Lactobacillus rhamnosus GG (LGG), having a drastic modification in its lipoteichoic acid (LTA) molecules, was analysed for its effects in an experimental colitis model. Dextran sulphate sodium (DSS) was used to induce either moderate to severe or mild chronic colitis in mice. Mice received either phosphate-buffered saline (PBS), LGG wild-type or the dltD mutant via the drinking water. Macroscopic parameters, histological abnormalities, cytokine and Toll-like receptor (TLR) expression were analysed to assess disease activity. LGG wild-type did not show efficacy in the different experimental colitis set-ups. This wild-type strain even seemed to exacerbate the severity of colitic parameters in the moderate to severe colitis model compared to untreated mice. In contrast, mice treated with the dltD mutant showed an improvement of some colitic parameters compared to LGG wild-type-treated mice in both experimental models. In addition, treatment with the dltD mutant correlated with a significant down-regulation of Toll-like receptor-2 expression and of downstream proinflammatory cytokine expression in the colitic mice. These results show that molecular cell surface characteristics of probiotics are crucial when probiotics are considered for use as supporting therapy in IBD.
虽然一些益生菌菌株可能在炎症性肠病(IBD)的治疗中有辅助作用,但这些作用仍存在争议,不能一概而论。在这项研究中,我们分析了模型益生菌鼠李糖乳杆菌 GG(LGG)的 dltD 突变体在实验性结肠炎模型中的作用,该突变体的脂磷壁酸(LTA)分子发生了剧烈改变。我们使用葡聚糖硫酸钠(DSS)诱导小鼠发生中度至重度或轻度慢性结肠炎。通过饮用水,小鼠分别接受磷酸盐缓冲盐水(PBS)、LGG 野生型或 dltD 突变体。分析宏观参数、组织学异常、细胞因子和 Toll 样受体(TLR)表达,以评估疾病活动度。LGG 野生型在不同的实验性结肠炎模型中均未显示出疗效。与未治疗的小鼠相比,该野生型菌株甚至在中度至重度结肠炎模型中似乎加重了结肠炎参数的严重程度。相比之下,在两种实验模型中,与 LGG 野生型治疗的小鼠相比,用 dltD 突变体治疗的小鼠的一些结肠炎参数有所改善。此外,用 dltD 突变体治疗与 TLR-2 表达和结肠炎小鼠下游促炎细胞因子表达的显著下调相关。这些结果表明,当考虑将益生菌作为 IBD 的辅助治疗时,益生菌的分子细胞表面特征至关重要。