IRSD, Université de Toulouse, INSERM, INRA, INP-ENVT, Université de Toulouse 3 Paul Sabatier, 31024, Toulouse, France.
CHU Toulouse, Hôpital Purpan, Service de bactériologie-hygiène, 31024, Toulouse, France.
Nat Commun. 2017 Nov 3;8(1):1314. doi: 10.1038/s41467-017-01403-9.
Administration of the probiotic Escherichia coli strain Nissle 1917 (EcN) decreases visceral pain associated with irritable bowel syndrome. Mutation of clbA, a gene involved in the biosynthesis of secondary metabolites, including colibactin, was previously shown to abrogate EcN probiotic activity. Here, we show that EcN, but not an isogenic clbA mutant, produces an analgesic lipopeptide. We characterize lipoamino acids and lipopeptides produced by EcN but not by the mutant by online liquid chromatography mass spectrometry. One of these lipopeptides, C12AsnGABAOH, is able to cross the epithelial barrier and to inhibit calcium flux induced by nociceptor activation in sensory neurons via the GABA receptor. C12AsnGABAOH inhibits visceral hypersensitivity induced by nociceptor activation in mice. Thus, EcN produces a visceral analgesic, which could be the basis for the development of new visceral pain therapies.
益生菌大肠杆菌菌株 Nissle 1917（EcN）的给药可减轻与肠易激综合征相关的内脏疼痛。先前的研究表明，参与包括 colibactin 在内的次生代谢物生物合成的 clbA 基因的突变会消除 EcN 的益生菌活性。在这里，我们表明 EcN 但不是同源的 clbA 突变体产生一种镇痛脂肽。我们通过在线液相色谱质谱法对 EcN 产生但突变体不产生的脂氨酸和脂肽进行了表征。这些脂肽之一，C12AsnGABAOH，能够穿过上皮屏障并通过 GABA 受体抑制感觉神经元中伤害感受器激活诱导的钙通量。C12AsnGABAOH 抑制小鼠中由伤害感受器激活引起的内脏敏感性。因此，EcN 产生一种内脏镇痛剂，这可能是开发新的内脏疼痛疗法的基础。
