Interactions Between Commensal Bacteria and Enteric Neurons, via FPR1 Induction of ROS, Increase Gastrointestinal Motility in Mice.
Interactions Between Commensal Bacteria and Enteric Neurons, via FPR1 Induction of ROS, Increase Gastrointestinal Motility in Mice.
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DOI：
10.1053/j.gastro.2019.03.045
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发表时间：
2019-07
期刊：
影响因子：
29.4
通讯作者：
Neish AS
中科院分区：
文献类型：
--
作者：
Chandrasekharan B;Saeedi BJ;Alam A;Houser M;Srinivasan S;Tansey M;Jones R;Nusrat A;Neish AS
胃肠道（GI）运动减少是与肠道生态失调和有益微生物丧失相关的疾病的一个特征。目前尚不清楚食用有益的共生微生物（以益生菌销售）如何影响肠道神经系统（ENS）。我们研究了广泛使用的益生菌及其共生菌鼠李糖乳杆菌GG （LGG）对小鼠ENS和GI运动的影响。用LGG灌胃常规和无菌C57B6小鼠，收集肠道组织；采用实时荧光定量PCR、免疫印迹和免疫染色检测肠道神经元亚型的变化。采用免疫印迹和免疫染色检测空肠肌丛活性氧（ROS）的产生和肠神经节中丝裂原活化蛋白激酶1 （MAPK1）的磷酸化(p)。用探针对空肠冷冻切片进行荧光原位杂交检测甲酰基肽受体1 （FPR1）。常规小鼠每天灌胃LGG 1周后，观察其胃肠运动。给小鼠喂食LGG刺激了肌内ROS的产生，增加了磷酸化MAPK1的水平，增加了神经元胆碱乙酰转移酶的表达（P< 0.001）。在给予n-乙酰半胱氨酸（一种ROS抑制剂）或LGGΩSpaC（一种LGG黏附突变株）或fpr1敲除小鼠的小鼠中没有观察到这些影响。在离体实验中，LGG灌胃1周显著增加了小鼠的大便次数，减少了胃肠道总转运时间，并增加了回肠环状肌条的收缩（P< 0.05）。通过小鼠模型，我们发现ENS中lgg介导的信号通路需要细菌粘附、氧化还原机制和FPR1。这一途径可能被激活以增加患者的胃肠道运动。LGG通过FPR1诱导的ROS激活粘膜下肠神经元和肌肠丛神经元p44/42 MAPK/Erk 1/2)的磷酸化，导致神经元分化，有利于胆碱能神经元（ChAT）并增强GI运动。NAC， ROS抑制剂和pilin缺陷突变体LGGΩSpaC，消除了LGG的作用，不能诱导ROS和下游Erk 1/2磷酸化以及随后的GI运动改善。
Reduced gastrointestinal (GI) motility is a feature of disorders associated with intestinal dysbiosis and loss of beneficial microbes. It is not clear how consumption of beneficial commensal microbes, marketed as probiotics, affects the enteric nervous system (ENS). We studied the effects of the widely used probiotic and the commensal Lactobacillus rhamnosus GG (LGG) on ENS and GI motility in mice. Conventional and germ-free C57B6 mice were gavaged with LGG and intestinal tissues were collected; changes in the enteric neuronal subtypes were assessed by real-time PCR, immunoblots and immunostaining. Production of reactive oxygen species (ROS) in the jejunal myenteric plexi and phosphorylation (p) of mitogen-activated protein kinase 1 (MAPK1) in the enteric ganglia were assessed by immunoblots and immunostaining. Fluorescence in situ hybridization was performed on jejunal cryosections with probes to detect formyl peptide receptor 1 (FPR1). GI motility in conventional mice was assessed after daily gavage of LGG for 1 week. Feeding of LGG to mice stimulated myenteric production of ROS, increased levels of phosphorylated MAPK1, and increased expression of choline acetyl transferase by neurons (P<.001). These effects were not observed in mice given N-acetyl cysteine (a ROS inhibitor) or LGGΩSpaC (an adhesion-mutant strain of LGG) or FPR1-knockout mice. Gavage of mice with LGG for 1 week significantly increased stool frequency, reduced total GI transit time, and increased contractions of ileal circular muscle strips in ex vivo experiments (P<.05). Using mouse models, we found that LGG-mediated signaling in the ENS requires bacterial adhesion, redox mechanisms, and FPR1. This pathway might be activated to increase GI motility in patients. LGG induced ROS via FPR1 activates phosphorylation of p44/42 MAPK/Erk 1/2) in the enteric neurons in sub mucosal and myenteric plexi neurons leading to neuronal differentiation that favors cholinergic neurons (ChAT) and enhances GI motility. NAC, the ROS inhibitor, and the pilin defective mutant LGGΩSpaC, abolishes the effects of LGG, and fails to induce ROS and downstream Erk 1/2 phosphorylation and subsequent improvements in GI motility.
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DOI：
10.1523/jneurosci.6684-10.2011
发表时间：
2011-06-15
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Li Z;Chalazonitis A;Huang YY;Mann JJ;Margolis KG;Yang QM;Kim DO;Côté F;Mallet J;Gershon MD
通讯作者：
Gershon MD
影响因子：
7.4
作者：
Lin, Patricia W.;Myers, Loren E. S.;Ray, Laurie;Song, Shuh-Chyung;Nasr, Tala R.;Berardinelli, Andrew J.;Kundu, Kousik;Murthy, Niren;Hansen, Jason M.;Neish, Andrew S.
通讯作者：
Neish, Andrew S.
影响因子：
8
作者：
通讯作者：
--
影响因子：
16.6
作者：
Mao, Yu-Kang;Kasper, Dennis L.;Kunze, Wolfgang A.
通讯作者：
Kunze, Wolfgang A.
DOI：
10.1073/pnas.0908876106
发表时间：
2009-10-06
影响因子：
11.1
作者：
Kankainen, Matti;Paulin, Lars;de Vos, Willem M.
通讯作者：
de Vos, Willem M.