Characterizing microbiota-independent effects of oligosaccharides on intestinal epithelial cells: insight into the role of structure and size : Structure-activity relationships of non-digestible oligosaccharides

Eur J Nutr. 2017 Aug;56(5):1919-1930. doi: 10.1007/s00394-016-1234-9. Epub 2016 Jun 13.

Abstract

Purpose: The direct effects of galacto-oligosaccharides (GOS), including Vivinal® GOS syrup (VGOS) and purified Vivinal® GOS (PGOS), on the epithelial integrity and corresponding interleukin-8 (IL-8/CXCL8) release were examined in a Caco-2 cell model for intestinal barrier dysfunction. To investigate structure-activity relationships, the effects of individual DP fractions of VGOS were evaluated. Moreover, the obtained results with GOS were compared with Caco-2 monolayers incubated with fructo-oligosaccharides (FOS) and inulin.

Methods: Caco-2 monolayers were pretreated (24 h) with or without specific oligosaccharides or DP fractions of VGOS (DP2 to DP6) before being exposed for 12 or 24 h to the fungal toxin deoxynivalenol (DON). Transepithelial electrical resistance and lucifer yellow permeability were measured to investigate barrier integrity. A calcium switch assay was used to study the reassembly of tight junction proteins. Release of CXCL8, a typical marker for inflammation, was quantified by ELISA.

Results: In comparison with PGOS, FOS and inulin, VGOS showed the most pronounced protective effect on the DON-induced impairment of the monolayer integrity, acceleration of the tight junction reassembly and the subsequent CXCL8 release. DP2 and DP3 in concentrations occurring in VGOS prevented the DON-induced epithelial barrier disruption, which could be related to their high prevalence in VGOS. However, no effects of the separate DP GOS fractions were observed on CXCL8 release.

Conclusions: This comparative study demonstrates the direct, microbiota-independent effects of oligosaccharides on the intestinal barrier function and shows the differences between individual galacto- and fructo-oligosaccharides. This microbiota-independent effect of oligosaccharides depends on the oligosaccharide structure, DP length and concentration.

Keywords: CXCL8; Caco-2 cells; Degree of polymerization; Intestinal permeability; Non-digestible oligosaccharides; Tight junctions.

MeSH terms

  • Caco-2 Cells
  • Epithelial Cells / drug effects*
  • Epithelial Cells / metabolism
  • Epithelial Cells / microbiology
  • Gastrointestinal Microbiome*
  • Humans
  • Interleukin-8 / metabolism
  • Intestines / cytology*
  • Intestines / microbiology
  • Inulin / pharmacology
  • Oligosaccharides / pharmacology*
  • Structure-Activity Relationship
  • Trichothecenes / toxicity

Substances

  • CXCL8 protein, human
  • Interleukin-8
  • Oligosaccharides
  • Trichothecenes
  • Inulin
  • deoxynivalenol