武汉云克隆科技股份有限公司

Abstract

BACKGROUND & AIMS:

Probiotics can reduce symptoms of irritable bowel syndrome (IBS), but little is known about their effects on psychiatric comorbidities. We performed a prospective study to evaluate the effects of Bifidobacterium longum NCC3001 (BL) on anxiety and depression in patients with IBS.

METHODS:

We performed a randomized, double-blind, placebo-controlled study of 44 adults with IBS and diarrhea or a mixed-stool pattern (based on Rome III criteria) and mild to moderate anxiety and/or depression (based on the Hospital Anxiety and Depression scale) at McMaster University in Canada, from March 2011 to May 2014. At the screening visit, clinical history and symptoms were assessed and blood samples were collected. Patients were then randomly assigned to groups and given daily BL (n = 22) or placebo (n = 22) for 6 weeks. At weeks 0, 6, and 10, we determined patients' levels of anxiety and depression, IBS symptoms, quality of life, and somatization using validated questionnaires. At weeks 0 and 6, stool, urine and blood samples were collected, and functional magnetic resonance imaging (fMRI) test was performed. We assessed brain activation patterns, fecal microbiota, urine metabolome profiles, serum markers of inflammation, neurotransmitters, and neurotrophin levels.

RESULTS:

At week 6, 14 of 22 patients in the BL group had reduction in depression scores of 2 points or more on the Hospital Anxiety and Depression scale, vs 7 of 22 patients in the placebo group (P = .04). BL had no significant effect on anxiety or IBS symptoms. Patients in the BL group had a mean increase in quality of life score compared with the placebo group. The fMRI analysis showed that BL reduced responses to negative emotional stimuli in multiple brain areas, including amygdala and fronto-limbic regions, compared with placebo. The groups had similar fecal microbiota profiles, serum markers of inflammation, and levels of neurotrophins and neurotransmitters, but the BL group had reduced urine levels of methylamines and aromatic amino acids metabolites. At week 10, depression scores were reduced in patients given BL vs placebo.

CONCLUSION:

In a placebo-controlled trial, we found that the probiotic BL reduces depression but not anxiety scores and increases quality of life in patients with IBS. These improvements were associated with changes in brain activation patterns that indicate that this probiotic reduces limbic reactivity. ClinicalTrials.gov no. NCT01276626.

摘要

背景和目的：

益生菌可以减少肠易激综合症（IBS）的症状，但它们对精神并发症的影响人们知之甚少。我们进行了一项前瞻性研究，以评估长双歧杆菌NCC3001（BL）对肠易激综合症患者的焦虑和抑郁情绪的影响。

方法：

我们从2011年3月至2014年5月在加拿大麦克马斯特大学进行了一项随机、双盲、安慰剂对照研究，针对44名患有肠易激综合症和腹泻的成年人或混合粪便模式（基于罗马III标准），并伴有轻度到中度焦虑和/或抑郁（基于医院的焦虑和抑郁量表）。在筛查访问中，对临床病史和症状进行了评估，并采集了血样。然后，病人被随机分配到不同组别中，并持续6周每天给BL（n=22）或安慰剂（n=22）。在第0、6和10周，通过经过验证的问卷调查，我们确定了患者的焦虑和抑郁程度、肠易激综合症症状、生活质量、以及躯体症状。在第0和6周，收集了粪便、尿液和血液样本，并进行了功能性核磁共振成像（fMRI）检测。我们评估了大脑激活模式、粪便微生物群、尿代谢组概况、炎症的血清标志物、神经递质和神经营养因子水平。

结果：

在第6周，BL组的22名患者中，根据医院焦虑和抑郁量表，有14名患者的抑郁分值减少了2分或更多，而在安慰剂组的22名患者中有7例（P=0.04）。BL对焦虑或肠易激综合症症状没有显著影响。与安慰剂组相比，BL组患者的生活质量平均得分增加。功能性核磁共振成像分析显示，与安慰剂相比，在多个大脑区域，包括杏仁核和额叶边缘区域，BL组对负面情绪刺激的反应减少了。这两组有类似的粪便微生物群概况，炎症的血清标志物，以及神经营养因子和神经递质的水平，但是BL组尿液中的甲胺和芳香族氨基酸代谢物的水平减少了。在第10周，和服用安慰剂的患者相比，服用BL的患者抑郁得分有所降低。

结论：

在一项安慰剂对照试验中，我们发现益生菌长双歧杆菌可以减少抑郁，但不能减少焦虑得分，并提高肠易激综合症患者的生活质量。这些改善与大脑激活模式的变化有关，这表明这些益生菌可以减少边缘反应。ClinicalTrials.gov no. NCT01276626.

使用试剂原文信息：Plasma neurotransmitters were quantified using following kits: 5-HT: IBL, Hamburg, Germany; Substance P: Abcam, Cambridge,UK; CGRP: Cloud-Clone Corp, Houston, TX.