Data_Sheet_1_Probiotic VSL#3 Treatment Reduces Colonic Permeability and Abdominal Pain Symptoms in Patients With Irritable Bowel Syndrome.pdf

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：目前关于益生菌VSL#3（probiotic VSL#3）的治疗方案及疗程对肠易激综合征（irritable bowel syndrome, IBS）患者肠道与微生物组功能的临床影响仍知之甚少。作为一项安全性试验的组成部分，本研究评估了VSL#3的治疗时长对腹痛、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干预。每日记录不良事件、腹痛症状及排便模式。分别于基线及治疗结束后，对肠道通透性、粪便胆汁酸水平及微生物组组成进行检测与分析。
结果：共计15名受试者完成本试验（4周组：n=8；8周组：n=7）。两组患者的腹痛发作次数均较基线减少（4周组P=0.049，8周组P=0.034）。通过全鸟枪法宏基因组测序分析，可在受试者粪便中检出VSL#3所含的益生菌菌株；试验结束时，嗜热链球菌（Streptococcus thermophilus）、动物双歧杆菌（Bifidobacterium animalis）、植物乳杆菌（Lactobacillus plantarum）及副干酪乳杆菌副干酪亚种（Lactobacillus casei subsp. paraccasei）的相对丰度与腹痛症状改善及结肠通透性改善呈显著相关。尽管试验结束时腹痛症状与益生菌菌株的检出情况呈显著相关，但肠道微生物组结构的整体分析显示，VSL#3干预后群落多样性及组成未发生明显变化。
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呈显著相关，提示未来可开展更大规模的随机对照试验，以探究VSL#3及结肠通透性在肠易激综合征病理生理过程中的作用机制。
临床试验注册：www.clinicaltrials.gov，标识符：NCT00971711。