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抗生素驱动的肠道运动变化提示对肠神经系统的直接调节。

Antibiotic Driven Changes in Gut Motility Suggest Direct Modulation of Enteric Nervous System.

作者信息

Delungahawatta Thilini, Amin Jessica Y, Stanisz Andrew M, Bienenstock John, Forsythe Paul, Kunze Wolfgang A

机构信息

Department of Medical Science, McMaster University, Hamilton, ON, Canada.

McMaster Brain-Body Institute, St. Joseph's Healthcare, Hamilton, ON, Canada.

出版信息

Front Neurosci. 2017 Oct 20;11:588. doi: 10.3389/fnins.2017.00588. eCollection 2017.

Abstract

Antibiotic-mediated changes to the intestinal microbiome have largely been assumed to be the basis of antibiotic-induced neurophysiological and behavioral changes. However, relatively little research has addressed whether antibiotics act directly on the host nervous system to produce these changes. We aimed to identify whether acute exposure of the gastrointestinal tract to antibiotics directly modulates neuronally dependent motility reflexes, . Motility of colon and jejunum segments in a perfusion organ bath was recorded by video and alterations to neuronally dependent propagating contractile clusters (PCC), measured using spatiotemporal maps of diameter changes. Short latency (<10 min) changes to PCC serve as an index of putative effects on the host nervous system. Bacitracin, penicillin V, and neomycin, all produced dose-dependent alterations to the velocity, frequency, and amplitude of PCC. Most significantly, colonic PCC velocity increased by 53% [probability of superiority (PS) = 87%] with 1.42 mg/ml bacitracin, 19% (PS = 81%) with 0.91 mg/ml neomycin, and 19% (PS = 86%) with 3.88 mg/ml penicillin V. Colonic frequency increased by 16% (PS = 73%) with 1.42 mg/ml bacitracin, 21% (PS = 79%) with 0.91 mg/ml neomycin, and 34% (PS = 85%) at 3.88 mg/ml penicillin V. Conversely, colonic amplitude decreased by 41% (PS = 79%) with 1.42 mg/ml bacitracin, 30% (PS = 80%) with 0.27 mg/ml neomycin and 25% (PS = 79%) at 3.88 mg/ml penicillin V. In the jejunum, antibiotic-specific changes were identified. Taken together, our findings provide evidence that acute exposure of the gastrointestinal lumen to antibiotics modulates neuronal reflexes. Future work should acknowledge the importance of this mechanism in mediating antibiotic-driven changes on gut-brain signaling.

摘要

抗生素介导的肠道微生物群变化在很大程度上被认为是抗生素诱导神经生理和行为变化的基础。然而,相对较少的研究探讨了抗生素是否直接作用于宿主神经系统以产生这些变化。我们旨在确定胃肠道急性暴露于抗生素是否直接调节神经元依赖性运动反射。通过视频记录灌注器官浴中结肠和空肠段的运动,并使用直径变化的时空图测量神经元依赖性传播收缩簇(PCC)的变化。PCC的短潜伏期(<10分钟)变化作为对宿主神经系统假定影响的指标。杆菌肽、青霉素V和新霉素均对PCC的速度、频率和幅度产生剂量依赖性改变。最显著的是,1.42mg/ml杆菌肽使结肠PCC速度增加53%[优势概率(PS)=87%],0.91mg/ml新霉素使结肠PCC速度增加19%(PS=81%),3.88mg/ml青霉素V使结肠PCC速度增加19%(PS=86%)。1.42mg/ml杆菌肽使结肠频率增加16%(PS=73%),0.91mg/ml新霉素使结肠频率增加21%(PS=79%),3.88mg/ml青霉素V使结肠频率增加34%(PS=85%)。相反,1.42mg/ml杆菌肽使结肠幅度降低41%(PS=79%),0.27mg/ml新霉素使结肠幅度降低30%(PS=80%),3.88mg/ml青霉素V使结肠幅度降低25%(PS=79%)。在空肠中,发现了抗生素特异性变化。综上所述,我们的研究结果提供了证据,表明胃肠道管腔急性暴露于抗生素会调节神经元反射。未来的工作应认识到这一机制在介导抗生素驱动的肠-脑信号变化中的重要性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb38/5655012/bc291596ddcc/fnins-11-00588-g0001.jpg

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