Glucagon-like peptide-2 improves intestinal immune function and diminishes bacterial translocation in a mouse model of parenteral nutrition

Nutr Res. 2018 Jan:49:56-66. doi: 10.1016/j.nutres.2017.10.007. Epub 2017 Oct 10.

Abstract

Parenteral nutrition (PN) is associated with increased infectious risks due to impaired intestinal immunity. Although glucagon-like peptide-2 (GLP-2) enhances the gut barrier function, it is uncertain whether it improves mucosal immunologic barrier function. We hypothesized that injecting the PN mouse model with GLP-2 improved innate and acquired immunity, and prevented bacterial translocation. Forty-eight hours after venous cannulation, male Institute of Cancer Research mice were randomly divided into 3 groups based on their diet: chow with saline (n = 10), PN (n = 9), or PN + GLP-2 (30 μg bid per mouse, n = 10) provided for 5 days. Compared with chow, PN reduced interleukin (IL)-4 and IL-13 levels (P < .05, respectively), whereas, compared with PN alone, GLP-2 injection increased IL-4 and IL-13 levels (P < .05, respectively). Compared with chow, PN considerably suppressed, whereas GLP-2 improved, secretory phospholipase A2 and cryptdin-4 expression. PN, compared with chow, considerably decreased lysozyme and polymeric immunoglobulin receptor levels, whereas, compared with PN, GLP-2 significantly increased these protein levels (P < .01, respectively). In tissue and luminal samples, compared with chow, PN reduced secretory immunoglobulin A levels (P < .05), whereas, compared with PN alone, GLP-2 increased secretory immunoglobulin A levels (P < .05). Functionally, more bacterial translocation was observed in the PN group compared with the chow group (P < .001), and GLP-2 injection decreased bacterial translocation to chow levels (P < .05). In summary, GLP-2 treatment may improve intestinal innate and acquired immunity, and prevent bacterial translocation in mice on total parenteral nutrition.

Keywords: Bacterial translocation; Glucagon-like peptide-2; Intestinal barrier; Intestinal immunity; Mice; Parenteral nutrition.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptive Immunity / drug effects*
  • Animals
  • Bacterial Translocation / drug effects*
  • Disease Models, Animal
  • Glucagon-Like Peptide 2 / pharmacology*
  • Immunity, Innate / drug effects*
  • Immunoglobulin A, Secretory / metabolism
  • Interleukin-13 / metabolism
  • Interleukin-4 / metabolism
  • Intestinal Mucosa / drug effects*
  • Intestinal Mucosa / immunology
  • Intestinal Mucosa / metabolism
  • Male
  • Mice, Inbred ICR
  • Muramidase / metabolism
  • Parenteral Nutrition*
  • Phospholipases A2 / metabolism
  • Random Allocation
  • Receptors, Polymeric Immunoglobulin / metabolism

Substances

  • Glucagon-Like Peptide 2
  • Immunoglobulin A, Secretory
  • Interleukin-13
  • Receptors, Polymeric Immunoglobulin
  • Interleukin-4
  • Phospholipases A2
  • Muramidase