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嗜酸乳杆菌 NCFM 影响功能性腹痛患者结肠黏膜阿片受体表达:一项随机临床研究。

Lactobacillus acidophilus NCFM affects colonic mucosal opioid receptor expression in patients with functional abdominal pain - a randomised clinical study.

机构信息

Department of Maternal and Child Health, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.

出版信息

Aliment Pharmacol Ther. 2014 Jul;40(2):200-7. doi: 10.1111/apt.12800. Epub 2014 May 22.

Abstract

BACKGROUND

In a recent double-blinded clinical trial, the probiotic combination of Lactobacillus acidophilus NCFM (L-NCFM) and B-LBi07 reduced bloating symptoms in patients with functional bowel disorders; an effect more evident in those who reported abdominal pain. In mice, L-NCFM but not B-LBi07 induced colonic mu-opioid receptor (MOR) and cannabinoid receptor 2 (CB2) expression, and reduced visceral sensitivity.

AIMS

To determine if L-NCFM was the active component in the clinical trial and to investigate the mechanism of action in humans with mild to moderate abdominal pain.

METHODS

Caucasian women (n = 20) 18-70 years with mild to moderate abdominal pain were enrolled in a double-blind, two-armed, single-centre study. Patients were given either L-NCFM alone or in combination with B-LBi07 for 21 days at a total dose of 2 × 10(10) CFU b.d. Colonic biopsies were collected during unsedated, unprepped flexible sigmoidoscopy before and at the end of probiotic consumption. mRNA and immunostaining were then performed on these biopsies. Patients kept symptom diaries for the 7 days prior to starting probiotic therapy and for the last 7 days of therapy.

RESULTS

L-NCFM alone, but not with B-LBi07, induced colonic MOR mRNA and protein expression, as well as downstream signalling, as measured by enterocyte STAT3-phosphorylation. In contrast, CB2 expression was decreased. Both treatment groups trended towards improvement in symptoms, but the study was insufficiently powered to draw meaningful conclusions.

CONCLUSIONS

Lactobacillus acidophilus NCFM modulates mu-opioid receptor expression and activity, while the combination of L-NCFM and B-LBi07 does not. This study provides a possible mechanism for action by which probiotics modulates pain sensation in humans (Clinical Trial Number: NCT01064661).

摘要

背景

在最近的一项双盲临床试验中,嗜酸乳杆菌 NCFM(L-NCFM)和 B-LBi07 的益生菌组合减少了功能性肠病患者的腹胀症状;在报告腹痛的患者中,这种效果更为明显。在小鼠中,L-NCFM 而不是 B-LBi07 诱导了结肠 μ-阿片受体(MOR)和大麻素受体 2(CB2)的表达,并降低了内脏敏感性。

目的

确定 L-NCFM 是否是临床试验中的活性成分,并研究其在轻度至中度腹痛患者中的作用机制。

方法

招募了 20 名 18-70 岁的白人女性,这些女性有轻度至中度腹痛,参与了一项双盲、双臂、单中心研究。患者在 21 天内每天接受 L-NCFM 单独或与 B-LBi07 联合治疗,剂量为 2×10(10) CFU b.d. 在未使用镇静剂、未准备好的软性乙状结肠镜检查期间收集结肠活检,在开始益生菌治疗前和治疗结束时。然后对这些活检进行 mRNA 和免疫染色。患者在开始益生菌治疗前的 7 天和治疗的最后 7 天内保持症状日记。

结果

仅 L-NCFM,而不是 L-NCFM 与 B-LBi07 的组合,诱导了结肠 MOR mRNA 和蛋白表达,以及下游信号,如肠细胞 STAT3 磷酸化所测量的。相比之下,CB2 表达减少。两组患者的症状均有改善趋势,但由于研究样本量不足,无法得出有意义的结论。

结论

嗜酸乳杆菌 NCFM 调节 μ-阿片受体的表达和活性,而 L-NCFM 和 B-LBi07 的组合则没有。本研究为益生菌调节人类疼痛感知的作用机制提供了可能(临床试验编号:NCT01064661)。

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