Partial enteral nutrition increases intestinal sIgA levels in mice undergoing parenteral nutrition in a dose-dependent manner

Int J Surg. 2018 Jan:49:74-79. doi: 10.1016/j.ijsu.2017.12.011. Epub 2017 Dec 14.

Abstract

Background and aims: Partial enteral nutrition (PEN) protects parenteral nutrition (PN) induced gut mucosal immunity impairment. However, the gastrointestinal function of most patients with PN is too poor to tolerate full dosage of PEN and no guidelines recommend PEN dose. We aimed to identify an optimal PEN dose and to understand the protective mechanism.

Methods: Mice were assigned to groups with total parenteral nutrition (TPN), total enteral nutrition (TEN), or various degrees of PEN with PN. Additionally, AS1517499 was used to inhibit STAT6. Five days after treatment, secretory immunoglobulin A (sIgA) levels of luminal washing fluid and JAK1-STAT6 signalling in ileum tissue of different groups were assessed.

Results: We found that TPN lowered luminal sIgA and down-regulated pIgR, phosphorylated JAK1 and STAT6, IL-4 and IL-13 as well relative to TEN. Moreover, 40% EN were lowest dose that reversed these detrimental consequences of PN to an equivalent level as TEN. The rescue of pIgR and luminal sIgA expression was decreased when the JAK1-STAT6 pathway was inhibited.

Conclusion: We conclude that 40% EN is the optimal PEN dose that reverses PN-induced impairment of gut mucosal immunity. Additionally, we hypothesise that this benefit involves activation of the JAK1-STAT6 pathway.

Keywords: Gut barrier; Mucosal immunity; Parenteral nutrition; Partial enteral nutrition; Secretory immunoglobulin A.

MeSH terms

  • Animals
  • Enteral Nutrition / adverse effects*
  • Enteral Nutrition / methods
  • Ileum / metabolism
  • Immune System Diseases / etiology*
  • Immunoglobulin A, Secretory / metabolism*
  • Intestinal Mucosa / immunology
  • Janus Kinase 1 / metabolism
  • Male
  • Mice
  • Parenteral Nutrition / adverse effects*
  • Parenteral Nutrition / methods
  • Pyrimidines / administration & dosage
  • STAT6 Transcription Factor / antagonists & inhibitors
  • Signal Transduction / immunology

Substances

  • 4-(benzylamino)-2-((2-(3-chloro-4-hydroxyphenyl)ethyl)amino)pyrimidine-5-carboxamide
  • Immunoglobulin A, Secretory
  • Pyrimidines
  • STAT6 Transcription Factor
  • Stat6 protein, mouse
  • Jak1 protein, mouse
  • Janus Kinase 1