Department of Immunology, Institute for Biological Research "Siniša Stanković", University of Belgrade, Belgrade, Serbia.
Laboratory for Molecular Microbiology, Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Belgrade, Serbia.
Sci Rep. 2019 Jan 29;9(1):918. doi: 10.1038/s41598-018-37505-7.
Gut microbiota dysbiosis has been considered the essential element in the pathogenesis of multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis (EAE). Antibiotics were administered orally to Dark Agouti (DA) rats early in their life with the aim of perturbing gut microbiota and investigating the effects of such intervention on the course of EAE. As a result, the diversity of the gut microbiota was reduced under the influence of antibiotics. Mainly, Firmicutes and Actinobacteria were replaced by Proteobacteria and Bacteroidetes, while decreased proportions of Clostridia and Bacilli classes were accompanied by an increase in Gamma-Proteobacteria in antibiotic-treated animals. Interestingly, a notable decrease in the Helicobacteraceae, Spirochaetaceae and Turicibacteriaceae was scored in antibiotic-treated groups. Also, levels of short chain fatty acids were reduced in the faeces of antibiotic-treated rats. Consequently, aggravation of EAE, paralleled with stronger immune response in lymph nodes draining the site of immunization, and increased inflammation within the CNS, were observed in antibiotic-treated DA rats. Thus, the alteration of gut microbiota leads to an escalation of CNS-directed autoimmunity in DA rats. The results of this study indicate that antibiotic use in early life may have subsequent unfavourable effects on the regulation of the immune system.
肠道微生物群落失调被认为是多发性硬化症及其动物模型实验性自身免疫性脑脊髓炎（EAE）发病机制的重要因素。在生命早期，通过口服给予 Dark Agouti（DA）大鼠抗生素，以扰乱肠道微生物群，并研究这种干预对 EAE 病程的影响。结果，抗生素的影响下，肠道微生物群落的多样性减少。主要是厚壁菌门和放线菌门被变形菌门和拟杆菌门取代，而梭菌纲和芽孢杆菌纲的比例下降伴随着γ-变形菌纲的增加。有趣的是，在抗生素处理的动物中，幽门螺旋杆菌科、螺旋体科和 Turicibacteriaceae 的数量明显减少。此外，抗生素处理大鼠的粪便中短链脂肪酸水平降低。因此，在抗生素处理的 DA 大鼠中观察到 EAE 加重，与免疫接种部位引流淋巴结的更强免疫反应以及中枢神经系统内炎症增加平行。因此，肠道微生物群落的改变导致 DA 大鼠中枢神经系统定向自身免疫的加剧。这项研究的结果表明，生命早期使用抗生素可能对免疫系统的调节产生后续的不利影响。
