Table_3_Probiotic VSL#3 Treatment Reduces Colonic Permeability and Abdominal Pain Symptoms in Patients With Irritable Bowel Syndrome.docx

Background: Little is known regarding the clinical impact of treatment and treatment duration of probiotic VSL#3 on gut and microbiome function in irritable bowel syndrome (IBS). As part of a safety trial, we assessed the effect of VSL#3 treatment duration on abdominal pain, stooling, gut permeability, microbiome composition and function.
Methods: Adults with IBS were randomized into an open label trial to receive the probiotic VSL#3 for 4 or 8 weeks. Adverse events, abdominal pain, and stooling patterns were recorded daily. Gut permeability, fecal bile acid levels, and microbiome composition were profiled at baseline and after treatment.
Results: Fifteen subjects completed the trial (4-week: n = 8; 8-week: n = 7). Number of pain episodes decreased in both groups (P = 0.049 and P = 0.034; 4- vs. 8-week, respectively). Probiotic organisms contained in VSL#3 were detected in feces by whole shotgun metagenomic sequencing analysis and relative abundances of Streptococcus thermophilus, Bifidobacterium animalis, Lactobacillus plantarum, and Lactobacillus casei subsp. paraccasei correlated significantly with improved abdominal pain symptoms and colonic permeability at study completion. Although abdominal pain correlated significantly with the detection of probiotic species at study completion, a composite view of gut microbiome structure showed no changes in community diversity or composition after VSL#3 treatment.
Conclusions: Probiotic organisms identified in stool correlated significantly with improvement in colonic permeability and clinical symptoms, prompting future studies to investigate the mechanistic role of VSL#3 and colonic permeability in IBS pathophysiology in a larger randomized controlled trial.
Clinical Trial Registration:www.clinicaltrials.gov, Identifier: NCT00971711.

背景：目前对于益生菌VSL#3的治疗方案及治疗时长在肠易激综合征（IBS）患者肠道及微生物组功能中的临床影响尚不清楚。本研究作为一项安全性试验的一部分，评估了VSL#3治疗时长对腹痛、排便情况、肠道通透性、微生物组组成与功能的影响。
方法：将肠易激综合征成年患者随机纳入开放标签试验，分别接受为期4周或8周的益生菌VSL#3治疗。每日记录不良事件、腹痛及排便模式。在基线及治疗结束后，对肠道通透性、粪便胆汁酸水平及微生物组组成进行检测分析。
结果：共计15名受试者完成本试验（4周组：n=8；8周组：n=7）。两组患者的疼痛发作次数均有所减少（4周组P=0.049，8周组P=0.034；分别对应两组）。通过全鸟枪宏基因组测序分析，在受试者粪便中检测到VSL#3所含的益生菌菌株；嗜热链球菌（Streptococcus thermophilus）、动物双歧杆菌（Bifidobacterium animalis）、植物乳杆菌（Lactobacillus plantarum）及干酪乳杆菌副干酪亚种（Lactobacillus casei subsp. paracasei）的相对丰度，在试验结束时与腹痛症状改善及结肠通透性改善显著相关。尽管试验结束时腹痛与益生菌菌株的检出显著相关，但对肠道微生物组结构的综合分析显示，VSL#3治疗后群落多样性及组成均无明显变化。
结论：粪便中检出的益生菌菌株与结肠通透性及临床症状的改善显著相关，这提示未来需开展更大样本量的随机对照试验，以探究VSL#3及结肠通透性在肠易激综合征病理生理学中的机制作用。
临床试验注册：www.clinicaltrials.gov，标识符：NCT00971711。