Abstract：
Alterations in the composition of the commensal microbiota (dysbiosis) seem to be a pathogenic component of functional gastrointestinal disorders, mainly irritable bowel syndrome (IBS), and might participate in the secretomotor and sensory alterations observed in these patients.We determined if a state antibiotics-induced intestinal dysbiosis is able to modify colonic pain-related and motor responses and characterized the neuro-immune mechanisms implicated in mice. A 2-week antibiotics treatment induced a colonic dysbiosis (increments in Bacteroides spp, Clostridium coccoides and Lactobacillus spp and reduction in Bifidobacterium spp). Bacterial adherence was not affected. Dysbiosis was associated with increased levels of secretory-IgA, up-regulation of the antimicrobial lectin RegIIIγ, and toll-like receptors (TLR) 4 and 7 and down-regulation of the antimicrobial-peptide Resistin-Like Molecule-β and TLR5. Dysbiotic mice showed less goblet cells, without changes in the thickness of the mucus layer. Neither macroscopical nor microscopical signs of inflammation were observed. In dysbiotic mice, expression of the cannabinoid receptor 2 was up-regulated, while the cannabinoid 1 and the mu-opioid receptors were down-regulated. In antibiotic-treated mice, visceral pain-related responses elicited by intraperitoneal acetic acid or intracolonic capsaicin were significantly attenuated. Colonic contractility was enhanced during dysbiosis. Intestinal dysbiosis induce changes in the innate intestinal immune system and modulate the expression of pain-related sensory systems, an effect associated with a reduction in visceral pain-related responses. Commensal microbiota modulates gut neuro-immune sensory systems, leading to functional changes, at least as it relates to viscerosensitivity. Similar mechanisms might explain the beneficial effects of antibiotics or certain probiotics in the treatment of IBS.
摘要：
共生微生物群（生态失调）组成的改变似乎是功能性胃肠道疾病的致病成分，主要是肠易激综合征（IBS），并可能参与在这些患者中观察到的分泌运动和感觉改变。我们确定了状态抗生素诱导的肠道生态失调是否能够改变结肠疼痛相关和运动反应，并表征了小鼠中涉及的神经免疫机制。为期2周的抗生素治疗引起结肠菌群失调（拟杆菌属的增加，球梭菌和乳杆菌属和双歧杆菌属的减少）。细菌粘附没有受到影响。菌群失调与分泌型IgA水平升高有关，抗微生物凝集素RegIIIγ的上调，和toll样受体（TLR）4和7以及抗微生物肽抵抗素样分子β和TLR5的下调。低生小鼠的杯状细胞较少，粘液层的厚度没有变化。未观察到炎症的宏观或微观迹象。在生态失调小鼠中，大麻素受体2的表达上调，而大麻素1和μ阿片受体下调。在抗生素治疗的小鼠中，腹膜内乙酸或结肠内辣椒素引起的内脏疼痛相关反应显著减弱.菌群失调期间结肠收缩力增强。肠道菌群失调会引起肠道先天免疫系统的变化，并调节疼痛相关感觉系统的表达，与内脏疼痛相关反应减少相关的效果。共生微生物群调节肠道神经免疫感觉系统，导致功能变化，至少与内脏敏感性有关.类似的机制可能解释了抗生素或某些益生菌在治疗IBS中的有益作用。
