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

Abstract

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.

The Role of Short-Chain Fatty Acids From Gut Microbiota in Gut-Brain Communication

“…Similar to observations in GF mice, perturbations of the gut microbiota by antibiotics systemically produce altered immune responses in experimental models, notably toward a pro-inflammatory profile (6). This is also true in the CNS, which becomes more prone to extreme inflammatory responses when the microbiota is depleted by antibiotics early in life (104). It was shown that antibiotic-induced perturbations in gut microbial diversity influence neuroinflammation with altered microglial morphology (105)(106)(107).…”

“…Multiple sclerosis (MS) is a neurodegenerative T-cell-mediated autoimmune disease of the CNS that mainly affects the myelin sheath around motor neurons. Among its etiological factors, the imbalance between pro and anti-inflammatory cells in the immune system seems to play an important role, which is highly affected by the gut microbiota composition and can be aggravated by dysbiosis (104,176,177). Given that SCFAs, mainly butyrate, are capable of inducing Treg polarization, modulation of the gut microbiota toward increased production of these metabolites could be an interesting therapeutic approach to MS.…”

Investigation of the Impacts of Antibiotic Exposure on the Diversity of the Gut Microbiota in Chicks

“…Host and environmental factors influence the gut composition; comparative environmental factors (diet, medicines, and antibiotics) are more dominant in shaping the host microbiota than the host genotype [8,14]. Understanding the impacts of antibiotics on the host-microbe relationship, including the biology of competitive exclusion or the protection of microbiome taxa, as well as the gene flow of symbiotic functions in the gut ecology, may reveal safety strategies for the treatment of infections while preserving beneficial intestinal ecology [15,16]. Therefore, the objective of this study was to investigate the impact of antibiotic exposure (enrofloxacin and diclazuril) for two weeks followed by a two week withdrawal period on the composition and function of the normal microbial colonization of chickens.…”

Gut microbiota and bronchopulmonary dysplasia

“…One possible explanation is that antibiotics lead to alterations in the taxonomy and functional diversity of the gut microbiota, prolonging the time to restore healthy colonization and increasing foreign pathogen invasion opportunities 25 . Antibiotics can also whittle down the concentrations of SCFA 20 , which are considered to have antibacterial and anti-inflammatory properties 26 . Besides this, antibiotics diminish the abundance ofLactobacillus , which may delay host weight gain 27 and further affect BPD 28 .…”