Effects of Bacillus subtilis on Epithelial Tight Junctions of Mice with Inflammatory Bowel Disease

J Interferon Cytokine Res. 2016 Feb;36(2):75-85. doi: 10.1089/jir.2015.0030. Epub 2015 Dec 31.

Abstract

Intestinal mucosal barrier dysfunction associated with inflammatory bowel disease (IBD). Effects of Bacillus subtilis on epithelial tight junctions (TJs) and intrinsic regulatory mechanisms of the intestine were studied in pursuit of better treatments for IBD. Fifty Balb/c mice given 5% dextran sulfate sodium (DSS) in tap water ad libitum over a 7-day period (to induce colitis) were randomly assigned to 4 test groups [DSS, DSS+B. subtilis, DSS+5 amino salicylic acid (5ASA), and DSS+B. subtilis+5ASA] to compare with normal controls. In the test groups DSS was administered daily by oral gavage in normal saline (0.2 mL), adding B. subtilis (1 × 10(8) CFU), 5ASA (6 mg), or both for respective test groups. Defecation, body weight, colitis score, pathological features, epithelial TJs proteins [claudin-1, occludin, junctional adhesion molecule (JAM)-A, and zona occludens (ZO)-1], and various cytokines [interleukin (IL)-6, IL-17, IL-23, and tissue necrosis factor (TNF)-α] were evaluated. Relative to the DSS group, disease activity index scores, and graded histologic damage were all significantly reduced by B. subtilis intake. All parameters declined even further when B. subtilis and 5ASA were combined. Analytic testing (immunohistochemical, western blot, and PCR) revealed progressive increase in TJ protein (claudin-1, occludin, JAM-A, and ZO-1) expression in DSS, DSS+B. subtilis, DSS+5ASA, DSS+B. subtilis+5ASA, and normal control groups (P < 0.05), whereas cytokine (IL-6, IL-17, IL-23, and TNF-α) expression similarly declined (P < 0.05). B. subtilis intake upregulated expression of TJ proteins (claudin-1, occludin, JAM-A, and ZO-1), for improved barrier function, and downregulated cytokine expression (IL-6, IL-17, IL-23, and TNF-α) to reduce intestinal epithelial damage.

MeSH terms

  • Animals
  • Bacillus subtilis / physiology*
  • Biomarkers
  • Disease Models, Animal
  • Female
  • Immunohistochemistry
  • Inflammatory Bowel Diseases / diagnosis
  • Inflammatory Bowel Diseases / genetics
  • Inflammatory Bowel Diseases / metabolism*
  • Inflammatory Bowel Diseases / microbiology*
  • Intestinal Mucosa / metabolism*
  • Intestinal Mucosa / microbiology*
  • Intestinal Mucosa / pathology
  • Intestinal Mucosa / ultrastructure
  • Male
  • Mice
  • Severity of Illness Index
  • Tight Junction Proteins / genetics
  • Tight Junction Proteins / metabolism
  • Tight Junctions / diagnostic imaging
  • Tight Junctions / metabolism*
  • Weight Loss

Substances

  • Biomarkers
  • Tight Junction Proteins