Kühbacher T, Ott S J, Helwig U, Mimura T, Rizzello F, Kleessen B, Gionchetti P, Blaut M, Campieri M, Fölsch U R, Kamm M A, Schreiber S
Department of General Internal Medicine, Kiel, Germany.
Gut. 2006 Jun;55(6):833-41. doi: 10.1136/gut.2005.078303. Epub 2006 Jan 9.
The intestinal microbiota plays a critical role in the pathophysiology of pouchitis, a major complication after ileal pouch anal anastomosis in patients with ulcerative colitis. Recently, controlled trials have demonstrated that probiotics are effective in maintenance of remission in pouchitis patients. However, the mechanism by which therapy with probiotics works remains elusive. This study explores the role of the bacterial and fungal flora in a controlled trial for maintenance of remission in pouchitis patients with the probiotic VSL#3 compound.
The mucosa associated pouch microbiota was investigated before and after therapy with VSL#3 by analysis of endoscopic biopsies using ribosomal DNA/RNA based community fingerprint analysis, clone libraries, real time polymerase chain reaction (PCR), and fluorescence in situ hybridisation. Patients were recruited from a placebo controlled remission maintenance trial with VSL#3.
Patients who developed pouchitis while treated with placebo had low bacterial and high fungal diversity. Bacterial diversity was increased and fungal diversity was reduced in patients in remission maintained with VSL#3 (p = 0.001). Real time PCR experiments demonstrated that VSL#3 increased the total number of bacterial cells (p = 0.002) and modified the spectrum of bacteria towards anaerobic species. Taxa specific clone libraries for Lactobacilli and Bifidobacteria showed that the richness and spectrum of these bacteria were altered under probiotic therapy.
Probiotic therapy with VSL#3 increases the total number of intestinal bacterial cells as well as the richness and diversity of the bacterial microbiota, especially the anaerobic flora. The diversity of the fungal flora is repressed. Restoration of the integrity of a "protective" intestinal mucosa related microbiota could therefore be a potential mechanism of probiotic bacteria in inflammatory barrier diseases of the lower gastrointestinal tract.
肠道微生物群在袋炎的病理生理学中起关键作用,袋炎是溃疡性结肠炎患者回肠袋肛管吻合术后的一种主要并发症。最近,对照试验表明益生菌对维持袋炎患者的缓解有效。然而,益生菌治疗起作用的机制仍不清楚。本研究在一项使用益生菌VSL#3化合物维持袋炎患者缓解的对照试验中,探讨细菌和真菌菌群的作用。
通过基于核糖体DNA/RNA的群落指纹分析、克隆文库、实时聚合酶链反应(PCR)和荧光原位杂交分析内镜活检样本,研究VSL#3治疗前后与袋相关的黏膜微生物群。患者来自一项使用VSL#3的安慰剂对照缓解维持试验。
在接受安慰剂治疗时发生袋炎的患者细菌多样性低而真菌多样性高。用VSL#3维持缓解的患者细菌多样性增加而真菌多样性降低(p = 0.001)。实时PCR实验表明,VSL#3增加了细菌细胞总数(p = 0.002),并使细菌谱向厌氧菌种改变。针对乳酸杆菌和双歧杆菌的分类群特异性克隆文库显示,在益生菌治疗下这些细菌的丰富度和谱发生了改变。
用VSL#3进行益生菌治疗可增加肠道细菌细胞总数以及细菌微生物群的丰富度和多样性,尤其是厌氧菌群。真菌菌群的多样性受到抑制。因此,恢复与“保护性”肠道黏膜相关微生物群的完整性可能是益生菌在下消化道炎症性屏障疾病中的潜在作用机制。