Long-lasting effects of early-life antibiotic treatment and routine animal handling on gut microbiota composition and immune system in pigs

PLoS One. 2015 Feb 6;10(2):e0116523. doi: 10.1371/journal.pone.0116523. eCollection 2015.

Abstract

Background: In intensive pig husbandry systems, antibiotics are frequently administrated during early life stages to prevent respiratory and gastro-intestinal tract infections, often in combination with stressful handlings. The immediate effects of these treatments on microbial colonization and immune development have been described recently. Here we studied whether the early life administration of antibiotics has long-lasting effects on the pig's intestinal microbial community and on gut functionality.

Methodology/principal findings: To investigate the long-lasting effect of early-life treatment, piglets were divided into three different groups receiving the following treatments: 1) no antibiotics and no stress, 2) antibiotics and no stress, and 3) antibiotics and stress. All treatments were applied at day four after birth. Sampling of jejunal content for community scale microbiota analysis, and jejunal and ileal tissue for genome-wide transcription profiling, was performed at day 55 (~8 weeks) and day 176 (~25 weeks) after birth. Antibiotic treatment in combination with or without exposure to stress was found to have long-lasting effects on host intestinal gene expression involved in a multitude of processes, including immune related processes.

Conclusions/significance: The results obtained in this study indicate that early life (day 4 after birth) perturbations have long-lasting effects on the gut system, both in gene expression (day 55) as well as on microbiota composition (day 176). At day 55 high variance was observed in the microbiota data, but no significant differences between treatment groups, which is most probably due to the newly acquired microbiota during and right after weaning (day 28). Based on the observed difference in gene expression at day 55, it is hypothesized that due to the difference in immune programming during early life, the systems respond differently to the post-weaning newly acquired microbiota. As a consequence, the gut systems of the treatment groups develop into different homeostasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn / genetics
  • Animals, Newborn / microbiology
  • Anti-Bacterial Agents / administration & dosage*
  • Anti-Bacterial Agents / pharmacology
  • Biodiversity
  • DNA, Bacterial / analysis
  • DNA, Bacterial / drug effects
  • Disaccharides / administration & dosage*
  • Gastrointestinal Microbiome / drug effects
  • Gene Expression Profiling
  • Gene Expression Regulation, Developmental / drug effects
  • Heterocyclic Compounds / administration & dosage*
  • Intestinal Mucosa / drug effects*
  • Intestinal Mucosa / microbiology
  • Intestinal Mucosa / physiology
  • Stress, Physiological
  • Sus scrofa / genetics*
  • Sus scrofa / microbiology*

Substances

  • Anti-Bacterial Agents
  • DNA, Bacterial
  • Disaccharides
  • Heterocyclic Compounds
  • tulathromycin

Associated data

  • GEO/GSE53170

Grants and funding

The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. DS, SAV, JMJR, and MAS were supported by the funding of Dutch Ministry of Economic Affairs, Central Veterinary Institute and Wageningen Livestock Research. JZ was supported by a fellowship of the China Scholarship Programme, and JZ, HGHJH and HS were supported by the European Union through the Interplay project, Grant agreement no. 227549).