Institute of Medical Research, Northwestern Polytechnical University, Xi`an, Shaanxi, 710072, P. R. China.
Department of Human Anatomy, Histology and Embryology & K.K. Leung Brain Research Centre, The Air Force Medical University, No. 169 Changle West Road, Xi'an, 710032, China.
Mol Brain. 2021 Mar 6;14(1):49. doi: 10.1186/s13041-021-00759-w.
Antibiotics affect gut microbial composition, leading to Gut-Brain-Axis imbalance and neurobehavioral changes. However, the intestinal dysbacteriosis associated behavior changes are not consistently reported. It is not clear whether these changes are transient or permanent. The neuroprotective effect of probiotics against intestinal dysbacteriosis induced alternations needs to be determined either. In the present study, oral antibiotic mixture including Ampicillin, Streptomycin, and Clindamycin was utilized to induce intestinal dysbacteriosis in mice. Antibiotics application triggered mechanical allodynia in von frey test and spontaneous pain in open field test. It also resulted in increased anxiety and depressive-like behaviors and damaged spatial memory performance. After application of probiotics, the mechanical allodynia and spontaneous pain were alleviated significantly. The anxiety behaviors, depressive-like behaviors and recognitive performance were ameliorative as well. By using Fos protein as a marker, it is found that the sensory, emotion and memory related brain regions were activated in mice with intestinal dysbacteriosis. Our study is not only helpful for enriching our basic knowledge for understanding the changed pain responses and related brain disorders in antibiotics-induced dysbacteriosis mice, but also beneficial for providing a more comprehensive mechanistic explanation for the regulation of antibiotics and probiotics on gut microbiota and relevant alternations in animal neurological behaviors.
抗生素会影响肠道微生物组成,导致“肠-脑轴”失衡和神经行为改变。然而,与肠道菌群失调相关的行为变化并不总是被报道。这些变化是暂时的还是永久性的尚不清楚。益生菌对肠道菌群失调引起的改变的神经保护作用也需要确定。在本研究中,使用氨苄青霉素、链霉素和克林霉素的混合抗生素溶液来诱导小鼠肠道菌群失调。抗生素的应用导致 von Frey 试验中的机械性痛觉过敏和旷场试验中的自发性疼痛。它还导致焦虑和抑郁样行为增加,并损害空间记忆表现。应用益生菌后,机械性痛觉过敏和自发性疼痛明显减轻。焦虑行为、抑郁样行为和认知表现也得到改善。通过使用 Fos 蛋白作为标志物,发现肠道菌群失调的小鼠的感觉、情绪和记忆相关脑区被激活。我们的研究不仅有助于丰富我们对理解抗生素诱导的菌群失调小鼠疼痛反应改变和相关脑紊乱的基本知识,而且有助于更全面地解释抗生素和益生菌对肠道微生物群的调节作用以及相关动物神经行为的改变。