Bacterial immune interaction in experimental colitis

J Dig Dis. 2013 Oct;14(10):526-35. doi: 10.1111/1751-2980.12079.

Abstract

Objectives: This study aimed to analyze the effects of 5-aminosalicylic acid (5-ASA) on intestinal microbiota and immune regulation in inflammatory bowel disease (IBD) and to investigate the correlation between intestinal microbiota and immune factors.

Methods: Colitis in mice was induced by oxazolone. The community composition of luminal and mucosal microbiota was analyzed by a terminal restriction fragment length polymorphism. The expression of occludin, toll-like receptor (TLR)-2, TLR-4 and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) p65 proteins were measured by immunohistochemistry and Western blot. Linear correlation between intestinal microbial community and the severity of the colitis or intestinal microbial community and expressions of immune factors were determined.

Results: Protective bacteria decreased while aggressive bacteria increased in the colitis group. The richness and diversity of both luminal and mucosal microbiota decreased in the colitis group the decrease was enhanced in the 5-ASA-treated group. The diversity of mucosal microbiota significantly correlated with the extent of the colitis. Expressions of occludin, TLR-2, TLR-4, tumor necrosis factor-α and NF-κB p65 were significantly correlated with the diversity of mucosal microbiota.

Conclusions: Mucosal microbiota are important in the pathogenesis of IBD. 5-ASA increases protective bacteria but decreases aggressive bacteria, thus inducing the new intestinal microbial homeostasis.

Keywords: immune system; inflammatory bowel disease; intestinal microbiota; mesalamine; terminal restriction fragment length polymorphism.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology
  • Bacteria / drug effects
  • Bacteria / immunology*
  • Colitis, Ulcerative / chemically induced
  • Colitis, Ulcerative / immunology
  • Colitis, Ulcerative / microbiology*
  • Colon / immunology
  • Disease Models, Animal
  • Female
  • Intestinal Mucosa / immunology
  • Intestinal Mucosa / microbiology
  • Mesalamine / pharmacology
  • Mice
  • Mice, Inbred BALB C
  • Microbiota / drug effects
  • Microbiota / immunology*
  • Occludin / metabolism
  • Oxazolone
  • Polymorphism, Restriction Fragment Length
  • Severity of Illness Index
  • Toll-Like Receptor 2 / metabolism
  • Toll-Like Receptor 4 / metabolism
  • Transcription Factor RelA / metabolism
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Occludin
  • Toll-Like Receptor 2
  • Toll-Like Receptor 4
  • Transcription Factor RelA
  • Tumor Necrosis Factor-alpha
  • Oxazolone
  • Mesalamine