Oral Bifidobacterium longum expressing alpha-melanocyte-stimulating hormone to fight experimental colitis

Drug Deliv. 2016 Jul;23(6):2058-64. doi: 10.3109/10717544.2015.1122672. Epub 2015 Dec 16.

Abstract

The oral delivery of peptides is a highly attractive treatment approach. However, the harsh environment of the gastrointestinal tract limits its application. Here, we utilize Bifidobacterium as a delivery system to orally deliver a potent anti-inflammatory but short duration peptide alpha-melanocyte-stimulating hormone (α-MSH) against experimental colitis. The aim of our study was to facilitate the efficient oral delivery of α-MSH. We designed a vector of pBDMSH and used it to construct a Bifidobacterium longum expressing α-MSH. We then determined the bioactivity of recombinant Bifidobacterium in lipopolysaccharide-induced inflammatory models of HT-29 cells. Finally, we used Bifidobacterium expressing α-MSH against dextran sulfate sodium (DSS)-induced ulcerative colitis mice. Results based on the myeloperoxidase activity, the levels of inflammatory cytokines TNF-α, IL-1β, IL-6, and IL-10 and the histological injury of colon tissue reveal recombinant Bifidobacterium was efficient in attenuating DSS-induced ulcerative colitis, suggesting an alternative way to use Bifidobacterium as a delivery system to deliver α-MSH for DSS-induced ulcerative colitis therapy.

Keywords: Bifidobacterium; colitis; peptide delivery; α-MSH.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Bifidobacterium longum
  • Colon / chemistry*
  • Colon / drug effects
  • Dextran Sulfate / chemistry*
  • HT29 Cells
  • Humans
  • Interleukin-10 / chemistry*
  • Interleukin-10 / pharmacology
  • Mice
  • Tumor Necrosis Factor-alpha / chemistry*
  • alpha-MSH / chemistry*
  • alpha-MSH / metabolism
  • alpha-MSH / pharmacology*

Substances

  • Anti-Inflammatory Agents
  • Tumor Necrosis Factor-alpha
  • Interleukin-10
  • alpha-MSH
  • Dextran Sulfate