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益生菌菌株 LKM512 对成人特应性皮炎的止痒作用。

Antipruritic effects of the probiotic strain LKM512 in adults with atopic dermatitis.

机构信息

Dairy Science and Technology Institute, Kyodo Milk Industry Co Ltd, Hinode, Tokyo, Japan.

Chitofuna Dermatology Clinic, Setagaya, Tokyo, Japan.

出版信息

Ann Allergy Asthma Immunol. 2014 Aug;113(2):209-216.e7. doi: 10.1016/j.anai.2014.05.002. Epub 2014 Jun 2.

Abstract

BACKGROUND

Evidence suggests that intestinal microbiota play an important role in the pathogenesis of atopic dermatitis (AD) through induction of immunosuppression and immune tolerance; however, the exact underlying mechanism is unclear. Few studies to date have examined the effects of probiotics on adult-type AD.

OBJECTIVE

To examine the effects of the probiotic Bifidobacterium animalis subsp lactis LKM512 on adult-type AD and the expression of metabolites that are known to be influenced by gut microbiota in fecal samples.

METHODS

Forty-four patients were randomly assigned to receive LKM512 or a placebo and underwent medical examinations. Fecal microbiota were analyzed with real-time polymerase chain reaction. Metabolomic analysis was conducted to search for antipruritic metabolites produced by intestinal bacteria using feces derived from 3 patients whose itch scores had improved using capillary electrophoresis with time-of-flight mass spectrometry. Antipruritic effects of kynurenic acid were observed using AD-induced NC/Nga mice.

RESULTS

LKM512 administration alleviated itch in AD patients compared with controls and improved the dermatology-specific quality-of-life scores when compared with the controls. Administration of LKM512 also increased the expression of the antipruritic and antinociceptive metabolite kynurenic acid (KYNA) in patients whose itch score had improved after LKM512 treatment. In mouse experiments, scratching behavior counts tended to be decreased by KYNA injection when compared with no treatment.

CONCLUSION

LKM512 administration may exert antipruritic effects by increasing KYNA production. LKM512 could therefore be a potentially effective therapeutic candidate for the reduction of pruritus.

TRIAL REGISTRATION

umin.ac.jp/ctr Identifier: UMIN000005695.

摘要

背景

有证据表明,肠道微生物群通过诱导免疫抑制和免疫耐受在特应性皮炎(AD)的发病机制中发挥重要作用;然而,其确切的潜在机制尚不清楚。迄今为止,很少有研究检查益生菌对成人型 AD 的影响。

目的

研究双歧杆菌亚种 lactis LKM512 对成人型 AD 的影响,以及对粪便样本中已知受肠道微生物影响的代谢物的表达。

方法

44 名患者被随机分配接受 LKM512 或安慰剂,并接受体检。实时聚合酶链反应分析粪便微生物群。使用毛细管电泳飞行时间质谱法从 3 名瘙痒评分改善的患者的粪便中寻找肠道细菌产生的止痒代谢物,进行代谢组学分析。使用 AD 诱导的 NC/Nga 小鼠观察犬尿氨酸的止痒作用。

结果

与对照组相比,LKM512 给药减轻了 AD 患者的瘙痒,并与对照组相比改善了皮肤病特定的生活质量评分。与 LKM512 治疗后瘙痒评分改善的患者相比,LKM512 给药还增加了止痒和镇痛代谢物犬尿氨酸(KYNA)的表达。在小鼠实验中,与未治疗相比,KYNA 注射时搔抓行为计数趋于减少。

结论

LKM512 给药可能通过增加 KYNA 的产生发挥止痒作用。因此,LKM512 可能是减少瘙痒的一种潜在有效治疗候选药物。

试验注册

umin.ac.jp/ctr 标识符:UMIN000005695。

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