Carlsson Anders H, Yakymenko Olena, Olivier Isabelle, Håkansson Fathima, Postma Emily, Keita Asa V, Söderholm Johan D
Department of Clinical and Experimental Medicine, Linköping University, and Department of Surgery, County Council of Östergötland , Linköping , Sweden.
Scand J Gastroenterol. 2013 Oct;48(10):1136-44. doi: 10.3109/00365521.2013.828773. Epub 2013 Aug 26.
OBJECTIVE. The intestinal microbiota plays a substantial role in the pathogenesis of inflammatory bowel disease (IBD). Faecalibacterium prausnitzii (FP) is underrepresented in IBD patients and have been suggested to have anti-inflammatory effects in mice. Increased intestinal permeability is common in IBD but the relationship between FP and intestinal barrier function has not been investigated. Our aim was to study treatment with FP supernatant on intestinal barrier function in a dextran sodium sulfate (DSS) colitis mice model. MATERIAL AND METHODS. C57BL/6 mice received 3% DSS in tap water ad libitum during five days to induce colitis. From day 3 the mice received a daily gavage with FP supernatant or broth during seven days. Ileum and colon were mounted in Ussing chambers for permeability studies with (51)Cr-EDTA and Escherichia coli K-12. Colon was saved for Western blot analyses of tight junction proteins. RESULTS. DSS-treated mice showed significant weight loss and colon shortening. Gavage with FP supernatant resulted in a quicker recovery after DSS treatment and less extensive colonic shortening. Ileal mucosa of DSS mice showed a significant increase in (51)Cr-EDTA-passage compared to controls. (51)Cr-EDTA passage was significantly decreased in mice receiving FP supernatant. No significant differences were observed in passage of E. coli K12. Western blots showed a trend to increased claudin-1 and claudin-2 expressions in DSS mice. CONCLUSIONS. Supernatant of FP enhances the intestinal barrier function by affecting paracellular permeability, and may thereby attenuate the severity of DSS-induced colitis in mice. These findings suggest a potential role of FP in the treatment of IBD.
目的。肠道微生物群在炎症性肠病（IBD）的发病机制中起重要作用。普拉梭菌（FP）在IBD患者中数量减少，且在小鼠中已被证明具有抗炎作用。肠道通透性增加在IBD中很常见，但FP与肠道屏障功能之间的关系尚未得到研究。我们的目的是在葡聚糖硫酸钠（DSS）诱导的结肠炎小鼠模型中研究FP上清液对肠道屏障功能的治疗作用。材料与方法。C57BL/6小鼠在5天内自由饮用含3% DSS的自来水以诱导结肠炎。从第3天起，小鼠连续7天每天接受FP上清液或肉汤灌胃。将回肠和结肠安装在尤斯灌流小室中，用（51）铬-乙二胺四乙酸（51Cr-EDTA）和大肠杆菌K-12进行通透性研究。保留结肠用于紧密连接蛋白的蛋白质印迹分析。结果。DSS处理的小鼠体重显著减轻，结肠缩短。用FP上清液灌胃导致DSS处理后恢复更快，结肠缩短程度更小。与对照组相比，DSS小鼠的回肠黏膜（51）Cr-EDTA通过率显著增加。接受FP上清液的小鼠（51）Cr-EDTA通过率显著降低。在大肠杆菌K12的通过率方面未观察到显著差异。蛋白质印迹显示DSS小鼠中闭合蛋白-1和闭合蛋白-2表达有增加趋势。结论。FP上清液通过影响细胞旁通透性增强肠道屏障功能，从而可能减轻DSS诱导的小鼠结肠炎的严重程度。这些发现提示FP在IBD治疗中可能具有潜在作用。
