The Role of Pathogenic Microbes and Commensal Bacteria in Irritable Bowel Syndrome
The Role of Pathogenic Microbes and Commensal Bacteria in Irritable Bowel Syndrome
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DOI：
10.1159/000268126
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发表时间：
2009-01-01
影响因子：
2.3
通讯作者：
Bercik, Premsyl
中科院分区：
文献类型：
--
作者：
Collins, Stephen;Verdu, Elena;Bercik, Premsyl
背景：肠易激综合征（IBS）反映了几种致病实体，包括一个亚组与低度结肠炎症。我们认为致病菌是触发因素，肠道细菌的紊乱维持了低度炎症，这反过来又导致肠道或大脑功能障碍。方法：在无特定病原体的条件下在小鼠中进行研究。内脏疼痛通过内脏反应进行评估，运动通过体内荧光透视和体外肌肉收缩进行评估。脑化学通过原位杂交进行评估，行为通过标准测试进行评估。使用基于16 s的RT-PCR和DGGE监测微生物群。结果如下：短暂感染旋毛虫线虫的小鼠表现出运动性和内脏知觉的变化，持续到感染后6周。这伴随着微生物群的改变和环氧合酶-2的上调，这可以通过抗炎剂或选定的益生菌治疗来逆转。为了研究微生物群的贡献，我们用口服抗生素治疗小鼠，并监测内脏感知和行为。抗生素治疗使微生物群发生了实质性变化，炎症活动略有增加，P物质或疼痛感知增加。口服而非全身性抗生素治疗会导致脑化学变化和焦虑样行为增加。结论：这些研究提供了概念证据，即病原微生物可诱导持续的肠道功能障碍，肠道微生物组成的变化可维持肠道功能障碍，并诱导行为变化，使人联想到高达60%的肠易激综合征患者中发生的精神共病。版权所有（C）2010 S. Karger AG，巴塞尔
Background: Irritable bowel syndrome (IBS) reflects several pathogenetic entities including a subgroup with low-grade colonic inflammation. We propose that pathogenic bacteria act as triggers and that disturbances of commensal bacteria maintain low-grade inflammation, that in turn leads to dysfunction in the gut or brain. Methods: Studies were performed in mice under specific pathogen-free conditions. Visceral pain was assessed by the visceromotor response and motility was assessed by in vivo fluoroscopy and in vitro by muscle contractility. Brain chemistry was assessed by in situ hybridization and behavior by standard tests. The microbiota was monitored using 16s-based RT-PCR and DGGE. Results: Mice transiently infected with the nematode Trichinella spiralis exhibited changes in motility and in visceral perception that persisted for up to 6 weeks post-infection. This was accompanied by alterations in the microbiota and an upregulation of cyclooxygenase-2 which could be reversed by treatment with anti-inflammatory agents or selected probiotics. To investigate the contribution of the microbiota, we treated mice with oral antibiotics and monitored visceral perception and behavior. Antibiotic therapy produced substantial changes in the microbiota, a small increment in inflammatory activity and an increase in substance P or pain perception. Oral, but not systemic antibiotic treatment, produced changes in brain chemistry and an increase in anxiety-like behavior. Conclusion: These studies provide proof of concept that pathogenic microbes can induce persistent gut dysfunction and that changes in microbial composition of the gut can maintain gut dysfunction as well as induce behavioral changes reminiscent of the psychiatric comorbidity that occurs in up to 60% of irritable bowel syndrome patients. Copyright (C) 2010 S. Karger AG, Basel