Effect of dietary additives on intestinal permeability in both Drosophila and a human cell co-culture

Dis Model Mech. 2018 Nov 28;11(12):dmm034520. doi: 10.1242/dmm.034520.

Abstract

Increased intestinal barrier permeability has been correlated with aging and disease, including type 2 diabetes, Crohn's disease, celiac disease, multiple sclerosis and irritable bowel syndrome. The prevalence of these ailments has risen together with an increase in industrial food processing and food additive consumption. Additives, including sugar, metal oxide nanoparticles, surfactants and sodium chloride, have all been suggested to increase intestinal permeability. We used two complementary model systems to examine the effects of food additives on gut barrier function: a Drosophila in vivo model and an in vitro human cell co-culture model. Of the additives tested, intestinal permeability was increased most dramatically by high sugar. High sugar also increased feeding but reduced gut and overall animal size. We also examined how food additives affected the activity of a gut mucosal defense factor, intestinal alkaline phosphatase (IAP), which fluctuates with bacterial load and affects intestinal permeability. We found that high sugar reduced IAP activity in both models. Artificial manipulation of the microbiome influenced gut permeability in both models, revealing a complex relationship between the two. This study extends previous work in flies and humans showing that diet can play a role in the health of the gut barrier. Moreover, simple models can be used to study mechanisms underlying the effects of diet on gut permeability and function.This article has an associated First Person interview with the first author of the paper.

Keywords: Alkaline phosphatase; Drosophila; Gut barrier function; Intestinal permeability.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkaline Phosphatase / metabolism
  • Animals
  • Cell Line
  • Coculture Techniques
  • Diet*
  • Dietary Sugars / pharmacology
  • Drosophila Proteins / metabolism
  • Drosophila melanogaster / cytology*
  • Food Additives / pharmacology*
  • Humans
  • Intestines / cytology*
  • Intestines / microbiology
  • Microbiota / drug effects
  • Permeability
  • Phenotype
  • Polysorbates / pharmacology
  • Sodium Chloride, Dietary / pharmacology
  • Sugars / metabolism
  • Ubiquitin-Protein Ligases / metabolism

Substances

  • Dietary Sugars
  • Drosophila Proteins
  • Food Additives
  • Polysorbates
  • Sodium Chloride, Dietary
  • Sugars
  • Smurf protein, Drosophila
  • Ubiquitin-Protein Ligases
  • Alkaline Phosphatase