Stress and antibiotics alter luminal and wall-adhered microbiota and enhance the local expression of visceral sensory-related systems in mice
Stress and antibiotics alter luminal and wall-adhered microbiota and enhance the local expression of visceral sensory-related systems in mice
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DOI：
10.1111/nmo.12154
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发表时间：
2013-08-01
影响因子：
3.5
通讯作者：
Martinez, V.
中科院分区：
文献类型：
--
作者：
Aguilera, M.;Vergara, P.;Martinez, V.
背景应激导致胃肠道神经免疫反应改变。我们描述了应激和肠道共生微生物区系之间的相互作用，以及它们在调节结肠对应激反应、炎症诱导、感觉相关标记物的表达和内脏敏感性方面的作用。方法给C57BL/6N雌性小鼠(7日龄，PO)注射广谱抗生素(杆菌素/新霉素，0.4 mg/只，每日1次)。同时，小鼠接受每天1h(7天)的心理应激(回避水应激)。用荧光原位杂交法对管腔和壁贴壁微生物区系进行了表征。用逆转录定量实时聚合酶链式反应(RT-qPCR)检测大麻素受体1和2(CB1/2)、色氨酸羟化酶1和2(TPH1/2)，用酶联免疫吸附试验(EL ISA)检测分泌型免疫球蛋白A(S-IgA)。在结肠内注射辣椒素后，评估内脏敏感性。关键结果抗生素不影响对压力的排便和内分泌反应。然而，抗生素使细菌总数减少了2.5倍，导致了特定的微生物失调，并有利于细菌壁的粘连。抗生素和压力的结合导致细菌数量的进一步减少和生物失调，并增强了细菌壁的粘附性。低氧小鼠体内S-Ig A水平升高。然而，没有观察到与诱导结肠炎相一致的变化。生物失调可上调CB2的表达，胁迫可上调CB2和TPH1的表达。应激可增强内脏疼痛相关反应，这一效应可通过抗生素治疗加以预防。结论：推论共生微生物区系和宿主-微生物区系的相互作用能够调节结肠内神经免疫内分泌系统的局部表达，从而导致内脏敏感性的调节。这些机制可能与微生物区系在胃肠道内稳态中的致病和保护作用有关。
Background Stress leads to altered gastrointestinal neuro-immune responses. We characterized the interaction between stress and gut commensal microbiota and their role modulating colonic responses to stress, the induction of inflammation, the expression of sensory-related markers, and visceral sensitivity. Methods C57BL/6N female mice were treated (7days, PO) with non-absorbable-broad spectrum antibiotics (bacitracin/neomycin, 0.4mg per mouse per day). Simultaneously, mice were subjected to a 1h per day (7days) session of psychological stress (water avoidance stress, WAS). Luminal and wall-adhered microbiota were characterized by fluorescent in situ hybridization. Cannabinoid receptors 1 and 2 (CB1/2), tryptophan hydroxylase 1 and 2 (TPH1/2), and inflammatory markers were quantified by reverse transcription-quantitative real-time PCR (RT-qPCR) and secretory-IgA (s-IgA) by ELISA. Visceral sensitivity was assessed after the intracolonic administration of capsaicin. Key Results Antibiotics did not affect the defecatory and endocrine responses to stress. However, antibiotics diminished by 2.5-folds total bacterial counts, induced a specific dysbiosis and favored bacterial wall adherence. Combining antibiotics and stress resulted in further reductions in bacterial counts and a dysbiosis, with enhanced bacterial wall adherence. Luminal s-IgA levels increased in dysbiotic mice. Nevertheless, no alterations consistent with the induction of colonic inflammation were observed. Dysbiosis upregulated CB2 expression and stress upregulated CB2 and TPH1 expression. Stress enhanced visceral pain-related responses, an effect prevented by antibiotic treatment. Conclusions & Inferences Manipulations of the commensal microbiota and the interaction host-microbiota are able to modulate the local expression of neuro-immune-endocrine systems within the colon, leading to a modulation of visceral sensitivity. These mechanisms might contribute to the pathogenic and protective roles of microbiota in gastrointestinal homeostasis.