Polyunsaturated fatty acids support epithelial barrier integrity and reduce IL-4 mediated permeability in vitro

Eur J Nutr. 2008 Jun;47(4):183-91. doi: 10.1007/s00394-008-0712-0. Epub 2008 May 22.

Abstract

Background: The intestinal mucosa functions as a barrier against harmful dietary and microbial antigens. An intact gut barrier forms a prerequisite for protection against infection and allergy. Both allergic and inflammatory mediators (e.g. IL-4, IFN-gamma) are known to compromise the epithelial barrier integrity by enhancing permeability. Breast milk provides protection against infection and allergy and contains polyunsaturated fatty acids (PUFA).

Aim of the study: Although PUFA are commonly used in infant formulas their effect on intestinal barrier is still poorly understood. Therefore the effects of distinct PUFA (n-6: LA, GLA, DGLA, AA; n-3: ALA, EPA, DHA) and a fat blend with PUFA composition similar to that of the human breast milk fat fraction, on barrier integrity were investigated.

Methods: Human intestinal epithelial cells (T84) were pre-incubated with individual PUFA or a lipase treated fat blend, with or without subsequent IL-4 exposure. Barrier integrity was evaluated by measuring transepithelial resistance and permeability. Membrane phospholipid composition was determined by capillary gas chromatography.

Results: DGLA, AA, EPA, DHA and to a lesser extend GLA enhanced basal TER and strongly reduced IL-4 mediated permeability, while LA and ALA were ineffective. Furthermore, the lipase treated fat blend effectively supported barrier function. PUFA were incorporated in the membrane phospholipid fraction of T84 cells.

Conclusions: Long chain PUFA DGLA, AA, EPA and DHA were particularly effective in supporting barrier integrity by improving resistance and reducing IL-4 mediated permeability. Fat blends that release specific PUFA upon digestion in the gastrointestinal tract may support natural resistance.

MeSH terms

  • Cells, Cultured
  • Chromatography, Gas
  • Dietary Fats, Unsaturated / metabolism
  • Dietary Fats, Unsaturated / pharmacology*
  • Drug Synergism
  • Epithelial Cells
  • Fatty Acids, Omega-3 / pharmacology
  • Fatty Acids, Omega-6 / pharmacology
  • Fatty Acids, Unsaturated / metabolism
  • Fatty Acids, Unsaturated / pharmacology*
  • Food Hypersensitivity / immunology
  • Food Hypersensitivity / prevention & control
  • Humans
  • Immunity, Mucosal / drug effects*
  • Immunity, Mucosal / physiology
  • Interleukin-4 / immunology
  • Interleukin-4 / metabolism*
  • Intestinal Mucosa / immunology
  • Intestinal Mucosa / microbiology
  • Intestinal Mucosa / physiology*
  • Milk, Human / chemistry
  • Milk, Human / immunology
  • Permeability / drug effects*

Substances

  • Dietary Fats, Unsaturated
  • Fatty Acids, Omega-3
  • Fatty Acids, Omega-6
  • Fatty Acids, Unsaturated
  • Interleukin-4