Polyunsaturated fatty acids support epithelial barrier integrity and reduce IL-4 mediated permeability in vitro
- First Online:
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-γ) 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.
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.
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.
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.
Keywordspermeability IL-4 polyunsaturated fatty acids arachidonic acid (AA) docosahexaenoic acid (DHA)
4 kDa FITC-dextran
- (LC-) PUFA
(Long chain-)polyunsaturated fatty acids
- 1.Alessandri JM, Guesnet P, Arfi TS, Durand G (1991) Changes in fatty acid composition during cell differentiation in the small intestine of suckling piglets. Biochim Biophys Acta 1086: 340–348Google Scholar
- 5.Berin MC, Yang PC, Ciok L, Waserman S, Perdue MH (1999) Role for IL-4 in macromolecular transport across human intestinal epithelium. Am J Physiol 276:C1046–C1052Google Scholar
- 7.Blight EG, Dyer WJ (1959) A rapid method of total lipid extraction and purification. Can J Med Sci 37:911–917Google Scholar
- 10.Chawla A, Karl PI, Fisher SE (1995) Effect of N-3 polyunsaturated fatty acid supplemented diet on neutrophil-mediated ileal permeability and neutrophil function in the rat. J Am Coll Nutr 14:258–263Google Scholar
- 11.Colgan SP, Resnick MB, Parkos CA, Delp-Archer C, McGuirk D, Bacarra AE, Weller PF, Madara JL (1994) IL-4 directly modulates function of a model human intestinal epithelium. J Immunol 153:2122–2129Google Scholar
- 16.Hosea Blewett HJ, Cicalo MC, Holland CD, Field CJ (2008) The immunological components of human milk. Adv Food Nutr Res 54:45–80Google Scholar
- 23.Li Q, Zhang Q, Zhang M, Wang C, Zhu Z, Li N, Li J (2008) Effect of n-3 polyunsaturated fatty acids on membrane microdomain localization of tight junction proteins in experimental colitis. Febs J 275:411–420Google Scholar
- 24.Liu AH (2001) Allergy and asthma prevention: the cup half full. Allergy Asthma Proc 22:333–336Google Scholar
- 25.Lopez-Pedrosa JM, Ramirez M, Torres MI, Gil A (1999) Dietary phospholipids rich in long-chain polyunsaturated fatty acids improve the repair of small intestine in previously malnourished piglets. J Nutr 129:1149–1155Google Scholar
- 27.Mitic LL, Van Itallie CM, Anderson JM (2000) Molecular physiology and pathophysiology of tight junctions I. Tight junction structure and function: lessons from mutant animals and proteins. Am J Physiol Gastrointest Liver Physiol 279:G250–G254Google Scholar
- 28.Morrison WR, Smith LM (1964) Preparation of fatty acid methyl esters and dimethylacetals from lipids with boron fluoride–methanol. J Lipid Res 53:600–608Google Scholar
- 30.Nusrat A, Turner JR, Madara JL (2000) Molecular physiology and pathophysiology of tight junctions. IV. Regulation of tight junctions by extracellular stimuli: nutrients, cytokines, and immune cells. Am J Physiol Gastrointest Liver Physiol 279:G851–G857Google Scholar
- 31.van Odijk J, Kull I, Borres MP, Brandtzaeg P, Edberg U, Hanson LA, Host A, Kuitunen M, Olsen SF et al (2003) Breastfeeding and allergic disease: a multidisciplinary review of the literature (1966–2001) on the mode of early feeding in infancy and its impact on later atopic manifestations. Allergy 58:833–843CrossRefGoogle Scholar
- 33.Reynier M, Sari H, d’Anglebermes M, Kye EA, Pasero L (1991) Differences in lipid characteristics of undifferentiated and enterocytic-differentiated HT29 human colonic cells. Cancer Res 51:1270–1277Google Scholar
- 38.Sanders SE, Madara JL, McGuirk DK, Gelman DS, Colgan SP (1995) Assessment of inflammatory events in epithelial permeability: a rapid screening method using fluorescein dextrans. Epithelial Cell Biol 4:25–34Google Scholar
- 44.Weaver LT, Laker MF, Nelson R (1984) Intestinal permeability in the newborn. Arch Dis Child 59:236–241Google Scholar