title: Polyunsaturated fatty acids support epithelial barrier integrity and reduce IL-4 mediated permeability in vitro.
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).
  
  
  OBJECTIVE
  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.
authors.affiliation: Danone Research, Centre for Specialised Nutrition, Wageningen, The Netherlands. l.e.m.willemsen@uu.nl
authors.forename: Linette E M
authors.initials: LE
authors.lastname: Willemsen
authors.forename: Marleen A
authors.initials: MA
authors.lastname: Koetsier
authors.forename: Martin
authors.initials: M
authors.lastname: Balvers
authors.forename: Christopher
authors.initials: C
authors.lastname: Beermann
authors.forename: Bernd
authors.initials: B
authors.lastname: Stahl
authors.forename: Eric A F
authors.initials: EA
authors.lastname: van Tol
mesh_terms: D002478:Cells, Cultured; D002849:Chromatography, Gas; D004042:Dietary Fats, Unsaturated / Q000378:metabolism / Q000494:pharmacology*; D004357:Drug Synergism; D004847:Epithelial Cells; D015525:Fatty Acids, Omega-3 / Q000494:pharmacology; D043371:Fatty Acids, Omega-6 / Q000494:pharmacology; D005231:Fatty Acids, Unsaturated / Q000378:metabolism / Q000494:pharmacology*; D005512:Food Hypersensitivity / Q000276:immunology / Q000517:prevention & control; D006801:Humans; D018928:Immunity, Mucosal / Q000187:drug effects* / Q000502:physiology; D015847:Interleukin-4 / Q000276:immunology / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000276:immunology / Q000382:microbiology / Q000502:physiology*; D008895:Milk, Human / Q000737:chemistry / Q000276:immunology; D010539:Permeability / Q000187:drug effects*
chemical_list: D004042:Dietary Fats, Unsaturated; D015525:Fatty Acids, Omega-3; D043371:Fatty Acids, Omega-6; D005231:Fatty Acids, Unsaturated; D015847:Interleukin-4