Zheng B, van Bergenhenegouwen J, van de Kant H J G, Folkerts G, Garssen J, Vos A P, Morgan M E, Kraneveld A D
1 Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, Universiteitsweg 99, 3584 CG Utrecht, the Netherlands.
2 Nutricia Research, Uppsalalaan 12, 3584 CT Utrecht, the Netherlands.
Benef Microbes. 2016;7(2):205-13. doi: 10.3920/bm2015.0037. Epub 2015 Dec 8.
Although interest in using probiotics to prevent and treat intestinal diseases is increasing, the effects of specific probiotic strains still remain unclear. Here, we assess the therapeutic effects of two probiotic strains, Lactobacillus rhamnosus NutRes 1 and Bifidobacterium breve NutRes 204 on a dextran sodium sulphate (DSS)-induced chronic murine colitis model. The chronic colitis was induced by two DSS treatment cycles with a rest period of 10 days (the remission or resolution phase). The probiotic supplementation was started during the resolution phase, after the first DSS treatment cycle, and continued until the end of the experiment. In addition to clinical observations made during the experiment, cellular infiltration was measured along with mRNA expression of pro-inflammatory cytokines, T cell-associated cytokines, and Toll like receptors (TLR) in the inflamed colon after second DSS treatment cycle. L. rhamnosus, but not B. breve, rapidly and effectively improved the DSS-induced bloody diarrhoea during the resolution phase. However, a contradictory effect by both probiotic strains on the faecal condition was found after re-induction of colitis. The worsening of the faecal condition was accompanied by a reduced number of neutrophils and increased expression of interferon-γ in the colons of DSS-treated mice. Furthermore, an increased expression of TLR2, TLR6 and pro-inflammatory markers including chemokine (C-C motif) ligand 2, interleukin (IL)-1β, tumour necrosis factor α and IL-6 was found in DSS-treated mice with L. rhamnosus supplementation. These results indicate that therapeutic administration of specific probiotics might be beneficial during the resolution phase of colitis. However, caution should be taken as specific probiotic treatments reduce neutrophil influx, which may be the reason of exacerbation of chronic colitis.
尽管使用益生菌预防和治疗肠道疾病的关注度日益增加,但特定益生菌菌株的效果仍不明确。在此,我们评估了两种益生菌菌株——鼠李糖乳杆菌NutRes 1和短双歧杆菌NutRes 204对葡聚糖硫酸钠(DSS)诱导的慢性小鼠结肠炎模型的治疗效果。慢性结肠炎通过两个DSS治疗周期诱导产生,中间有10天的休息期(缓解或消退期)。在第一个DSS治疗周期后的消退期开始补充益生菌,并持续至实验结束。除了在实验过程中进行临床观察外,在第二个DSS治疗周期后,还测量了炎症结肠中的细胞浸润情况以及促炎细胞因子、T细胞相关细胞因子和Toll样受体(TLR)的mRNA表达。鼠李糖乳杆菌而非短双歧杆菌在消退期迅速且有效地改善了DSS诱导的血性腹泻。然而,在结肠炎再次诱导后,发现两种益生菌菌株对粪便状况均产生了矛盾的影响。粪便状况的恶化伴随着DSS处理小鼠结肠中中性粒细胞数量的减少和干扰素-γ表达的增加。此外,在补充鼠李糖乳杆菌的DSS处理小鼠中,发现TLR2、TLR6以及包括趋化因子(C-C基序)配体2、白细胞介素(IL)-1β、肿瘤坏死因子α和IL-6在内的促炎标志物的表达增加。这些结果表明,在结肠炎的消退期给予特定益生菌进行治疗可能有益。然而,应谨慎使用,因为特定的益生菌治疗会减少中性粒细胞的流入,这可能是慢性结肠炎加重的原因。