Oral neonatal antibiotic treatment perturbates gut microbiota and aggravates central nervous system autoimmunity in Dark Agouti rats

BackgroundGut microbiota dysbiosis has been considered as the essential element in the pathogenesis of multiple sclerosis, a chronic inflammatory, demyelinating and neurodegenerative disorder of the central nervous system (CNS). Experimental autoimmune encephalomyelitis (EAE) is an autoimmune disease of the CNS that is widely used as an animal model of multiple sclerosis. Dark Agouti (DA) rats are prone to EAE and it has previously been shown that they have less diverse gut microbiota in comparison to a strain of EAE-resistant rats. ResultsAntibiotics were applied orally to DA rats early in their life hood in the aim to perturbate gut microbiota and to investigate effects of such intervention on EAE course. As the result, marked changes in gut microbiota composition were observed. Generally, diversity of the microbiota was reduced under the influence of antibiotics. Mainly Firmicutes and Actinobacteria were replaced by Proteobacteria and Bacteroidetes, while decreased proportion of Clostridia and Bacilli class was accompanied with increase in Gamma-Proteobacteria in antibiotic treated animals. Interestingly, 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 was observed in antibiotic-treated DA rats. Increased severity of EAE was paralleled with stronger immune response in lymph nodes draining the site of immunization and increased inflammation within the CNS. ConclusionsThe alteration of gut microbiota leads to escalation of CNS-directed autoimmunity in DA rats. Thus, the results of this study indicate that antibiotic use in early life may have subsequent unfavourable effects on the regulation of the immune system.