Tryptophan-synthesizing bacteria enhance colonic motility.
Tryptophan-synthesizing bacteria enhance colonic motility.
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色氨酸合成细菌增强结肠蠕动。
DOI：
10.1111/nmo.14629
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发表时间：
2023
影响因子：
3.5
通讯作者：
Mawe,GaryM
中科院分区：
文献类型：
--
作者：
Legan,TheresaB;Lavoie,Brigitte;Norberg,Emilia;Ley,IsabellaC;Tack,Stephanie;Tompkins,ThomasA;Wargo,MatthewJ;Mawe,GaryM
背景一种新兴的治疗胃肠道（GI）动力障碍症状的策略是使用分离的细菌。然而，这些细菌剂的潜在作用机制尚未完全确立。在这里，我们阐明了一种新的方法，以促进肠道蠕动，利用特定细菌的生化能力，产生5-羟色胺（5-HT）前体，色氨酸（Trp）。枯草芽孢杆菌（R 0179）、热灭活的R 0179或B.枯草芽孢杆菌（1A 2）。测量Trp、5-HT和5-羟基吲哚乙酸（5-HIAA）的组织水平，并评估运动性的变化。与溶媒处理的小鼠相比，枯草杆菌R 0179表现出更高的Trp和5-HT分解产物5-HIAA的结肠组织水平。此外，B.枯草杆菌治疗加速了健康小鼠和便秘小鼠模型的结肠运动。在热灭活R 0179或不表达色氨酸合酶的活1A 2菌株中未观察到这些效应。最后，我们发现B.枯草杆菌R 0179被5-HT 4受体（5-HT 4 R）拮抗剂的共同给药所阻断，并且在5-HT 4 R敲除小鼠中不存在。结论和推论总之，这些数据表明，肠蠕动可以通过用合成Trp的细菌处理来增强，这可能是通过增加5-HT信号传导和/或Trp代谢物的作用以及5-HT 4 R的参与。我们的研究结果提供了一个短暂的和可预测的细菌策略，以促进胃肠道运动机制的见解。
BackgroundAn emerging strategy to treat symptoms of gastrointestinal (GI) dysmotility utilizes the administration of isolated bacteria. However, the underlying mechanisms of action of these bacterial agents are not well established. Here, we elucidate a novel approach to promote intestinal motility by exploiting the biochemical capability of specific bacteria to produce the serotonin (5‐HT) precursor, tryptophan (Trp).MethodsMice were treated daily for 1 week by oral gavage ofBacillus (B.) subtilis(R0179), heat‐inactivated R0179, or a tryptophan synthase‐null strain ofB. subtilis(1A2). Tissue levels of Trp, 5‐HT, and 5‐hydroxyindoleacetic acid (5‐HIAA) were measured and changes in motility were evaluated.Key resultsMice treated withB. subtilisR0179 exhibited greater colonic tissue levels of Trp and the 5‐HT breakdown product, 5‐HIAA, compared to vehicle‐treated mice. Furthermore,B. subtilistreatment accelerated colonic motility in both healthy mice as well as in a mouse model of constipation. These effects were not observed with heat‐inactivated R0179 or the live 1A2 strain that does not express tryptophan synthase. Lastly, we found that the prokinetic effects ofB. subtilisR0179 were blocked by coadministration of a 5‐HT4receptor (5‐HT4R) antagonist and were absent in 5‐HT4R knockout mice.Conclusions and inferencesTaken together, these data demonstrate that intestinal motility can be augmented by treatment with bacteria that synthesize Trp, possibly through increased 5‐HT signaling and/or actions of Trp metabolites, and involvement of the 5‐HT4R. Our findings provide mechanistic insight into a transient and predictable bacterial strategy to promote GI motility.