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长双歧杆菌 NCC3001 益生菌可降低抑郁评分并改变大脑活动:一项在肠易激综合征患者中的初步研究。

Probiotic Bifidobacterium longum NCC3001 Reduces Depression Scores and Alters Brain Activity: A Pilot Study in Patients With Irritable Bowel Syndrome.

机构信息

Department of Medicine, Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, ON, Canada.

Department of Psychology, Neuroscience, and Behavior, McMaster University, Hamilton, ON, Canada.

出版信息

Gastroenterology. 2017 Aug;153(2):448-459.e8. doi: 10.1053/j.gastro.2017.05.003. Epub 2017 May 5.

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

背景与目的

益生菌可以减轻肠易激综合征(IBS)的症状,但对其治疗精神共病的效果知之甚少。我们进行了一项前瞻性研究,以评估长双歧杆菌 NCC3001(BL)对 IBS 患者焦虑和抑郁的影响。

方法

我们在加拿大麦克马斯特大学进行了一项随机、双盲、安慰剂对照的研究,纳入了 44 名符合罗马 III 标准的 IBS 腹泻或混合排便模式(IBS-D 或 IBS-M)且伴有轻至中度焦虑和/或抑郁(基于医院焦虑和抑郁量表)的成年人。在筛选就诊时,评估了临床病史和症状并采集了血样。然后,患者被随机分配到 BL 组(n=22)或安慰剂组(n=22),并接受为期 6 周的每日 BL 或安慰剂治疗。在第 0、6 和 10 周时,我们使用经过验证的问卷评估了患者的焦虑和抑郁程度、IBS 症状、生活质量和躯体化。在第 0 和 6 周时,采集了粪便、尿液和血液样本,并进行了功能磁共振成像(fMRI)检查。我们评估了大脑激活模式、粪便微生物群、尿液代谢组谱、血清炎症标志物、神经递质和神经营养因子水平。

结果

在第 6 周时,BL 组有 14 名患者的医院焦虑和抑郁量表评分下降了 2 分或更多,而安慰剂组只有 7 名患者(P=0.04)。BL 对焦虑或 IBS 症状没有显著影响。与安慰剂组相比,BL 组患者的生活质量评分平均升高。fMRI 分析显示,与安慰剂相比,BL 组可降低杏仁核和额-边缘区域等多个脑区对负面情绪刺激的反应。两组粪便微生物群谱、血清炎症标志物以及神经营养因子和神经递质水平相似,但 BL 组尿液中甲基胺和芳香族氨基酸代谢物水平降低。在第 10 周时,与安慰剂相比,BL 组患者的抑郁评分降低。

结论

在一项安慰剂对照试验中,我们发现益生菌 BL 可降低 IBS 患者的抑郁评分,但不能降低焦虑评分,并提高其生活质量。这些改善与大脑激活模式的变化有关,表明这种益生菌可降低边缘反应性。ClinicalTrials.gov 注册号:NCT01276626。

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