Oligosaccharides isolated from goat milk reduce intestinal inflammation in a rat model of dextran sodium sulfate-induced colitis

      Summary

      Background and aims

      There is increased interest in the study of manipulation of the flora with pro- and prebiotics regarding inflammatory bowel disease. The aim of this work was to evaluate the effect of oligosaccharides from goat milk in a rat model of dextran sodium sulfate- (DSS-) induced colitis.

      Methods

      Twenty rats were fed the same diet but with different sources of fiber (5% of the diet): cellulose or a mixture of goat's milk oligosaccharides (GMO) and cellulose. DSS treatment was used to induce a colonic inflammation. Several clinical and inflammatory parameters, as well as intestinal micorbiota and gene expression by DNA microarray technology, were evaluated.

      Results

      DSS induced a decrease in body weight which was not observed in rats fed the GMO (decrease of 21±11% in control rats vs increase of 5.2±8.6 in GMO rats, P < 0.0 5 ). DSS also caused an acute colonic inflammatory process which was weaker in rats fed the GMO, as shown by colon myeloperoxidase activity (0.53±0.16 vs 0.14±0.07U/mg of protein, P < 0.0 5 ), as well as clinical symptoms measured by a scoring system (1.25±1.14 vs 0.4±0.07, P < 0.0 5 ). GMO rats also showed less severe colonic lesions and a more favorable intestinal microbiota. The expression of genes involved in intestinal function, such as mucine-3, was down-regulated in DSS-control rats but returned to normal values in GMO rats.

      Conclusion

      GMO reduce intestinal inflammation and contribute to the recovery of damaged colonic mucosa.

      Keywords

      Abbreviations:

      DSS (Dextran sodium sulfate), GMO (Goat's milk oligosaccharides), IBD (Inflammatory bowel disease), MPO (Myeloperoxidase), PF (Pair-fed), SCFA (Short-chain fatty acids)
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic and Personal
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Clinical Nutrition
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Riddell R.H.
        Pathology of idiopathic inflammatory bowel diseases.
        in: Kirsner J.B. Shorter R.G. Inflammatory bowel diseases. Lea and Febiger, Philadelphia1998: 329-350
        • Lauritsen K.
        Drug treatment and formation of eicosanoids in patients with chronic inflammatory bowel diseases.
        Dan Med Bull. 1989; 36: 378-393
        • Elson C.
        • et al.
        Experimental models of inflammatory bowel disease.
        Gastroenterology. 1995; 109: 1344-1367
        • Shanahan F.
        Probiotics in inflammatory bowel disease—therapeutic rationale and role.
        Adv Drug Deliver Rev. 2004; 56: 809-818
        • Chandran P.
        • Satthaporn S.
        • Robins A.
        • Eremin O.
        Inflammatory bowel disease: dysfunction of GALT and gut bacterial flora (II).
        Surgeon. 2003; 1: 125-136
        • Osman N.
        • Adawi D.
        • Ahrne S.
        • Jeppsson B.
        • Molin G.
        Modulation of the effect of dextran sulfate sodium-induced acute colitis by the administration of different probiotic strains of Lactobacillus and Bifidobacterium.
        Dig Dis Sci. 2004; 49: 320-327
        • Araki Y.
        • Andoh A.
        • Takizawa J.
        • Takizawa W.
        • Fujiyama Y.
        Clostridium butyricum, a probiotic derivative, suppresses detran sulfate sodium-induced experimental colitis in rats.
        Int J Mol Med. 2004; 13: 577-580
        • Rumi G.
        • Tsubouchi R.
        • Okayama M.
        • Kato S.
        • Mozsik G.
        • Takeuchi K.
        Protective effect of lactulose on dextran sulphate sodium-induced colonic inflammation in rats.
        Dig Dis Sci. 2004; 49: 1466-1472
        • Kanauchi O.
        • Andoh A.
        • Iwanaga T.
        • et al.
        Germinated barley foodstuffs attenuate colonic mucosal damage and mucosal nuclear factor κB in a spontaneous colitis model.
        J Gastroenterol Hepatol. 1999; 14: 1173-1179
        • Kunz C.
        • Rudloff S.
        • Baier W.
        • et al.
        Oligosaccharides in human milk: structural, functional and metabolic aspects.
        Annu Rev Nutr. 2000; 20: 699-722
        • Mc Guire W.
        • Anthony M.Y.
        Donor human milk versus formula for preventing necrotising enterocolitis in preterm infants: systematic review.
        Arch Dis Child Fetal Neonatal. 2003; 88: F11-F14
        • Martínez-Férez A.
        • Rudolff S.
        • Guadix A.
        • et al.
        Goat's milk as a natural source of lactose-derived oligosaccharides: isolation by membrane technology.
        Int Dairy J. 2005; 16: 173-181
        • Okayasu I.
        • Hatakeyama S.
        • Yamada M.
        • Ohkusa T.
        • Inagaki Y.
        • Nakaya R.
        A novel method in the induction of reliable experimental acute and chronic ulcerative colitis in mice.
        Gastroenterology. 1990; 98: 694-702
        • Mercier S.
        • Breuillé D.
        • Mosoni L.
        • et al.
        Chronic inflammation alters protein metabolism in several organs of adult rats.
        J Nutr. 2002; 132: 1921-1928
        • Stucchi A.F.
        • Shofer S.
        • Leeman S.
        • et al.
        NK-1 antagonist reduces colonic inflammation and oxidative stress in dextran sulfate sodium colitis in rats.
        Am J Physiol. 2000; 279: G1298-G1306
        • Iwai A.
        • Iwashita E.
        Changes in colonic inflammation induced by dextran sulphate sodium (DSS) during short- and long-term administration of rebamipide.
        Dig Dis Sci. 1998; 43: 143S-147S
        • Krawisz J.E.
        • Sharon P.
        • Stenson W.F.
        Quantitative assay for acute intestinal inflammation in rat and hamster models.
        Gastroenterology. 1984; 84: 1344-1350
        • Martin J.
        • White I.N.H.
        Fluorimetric determination of oxidised and reduced glutathione in cells and tissues by high-performance liquid chromatography following derivatization with dansyl chloride.
        J Chromatogr B Biomed Appl. 1991; 568: 219-225
        • Araki Y.
        • Andoh A.
        • Tsujikawa T.
        • et al.
        Alterations in intestinal microflora, faecal bile acids and short chain fatty acids in dextran sulphate sodium-induced experimental acute colitis in rats.
        Eur J Gastroenterol Hepatol. 2001; 13: 107-111
        • Mortensen P.B.
        • Clausen M.R.
        Short-chain fatty acids in the human colon: relation to gastrointestinal health and disease.
        Scand J Gastroenterol. 1996; 31: 132S-148S
        • Hoffmann P.
        • Reinshagen M.
        • Zeeh J.M.
        • et al.
        Increased expression of epidermal growth factor-receptor in an experimental model of colitis in rats.
        Scand J Gastroenterol. 2000; 35: 1174-1180
        • Spisni E.
        • Manica F.
        • Tomasi V.
        Involvement of prostanoids in the regulation of angiogenesis by polypeptide growth factors.
        Prostaglandins Leukot Essent Fatty Acids. 1992; 47: 111-115
        • Sanchez de Medina F.
        • Martinez-Augustin O.
        • Gonzalez R.
        • et al.
        Induction of alkaline phosphatase in the inflamed intestine: a novel pharmacological target for inflammatory bowel disease.
        Biochem Pharmacol. 2004; 68: 2317-2326
        • Guarner F.
        • Malagelada J.R.
        Role of bacteria in experimental colitis.
        Best Pract Res Clin Gastroenterol. 2003; 17: 793-804
        • Perán L.
        • Camuesco D.
        • Comalada M.
        • et al.
        Preventive effects of a probiotic Lactobacllus salivarius ssp.sallivarius in the TNBS model of rat colitis.
        World J Gastroenterol. 2005; 11: 5185-5192
        • Otte J.M.
        • Podolsky D.K.
        Functional modulation of enterocytes by gram-positive and gram-negative microorganisms.
        Am J Physiol Gastrointest Liver Physiol. 2004; 286: G613-G626
        • Videla S.
        • Vilaseca J.
        • Antolin M.
        • et al.
        Dietary inulin improves distal colitis induced by dextran sodium sulfate in the rat.
        Am J Gastroenterol. 2001; 96: 1486-1493
        • Moreau N.M.
        • Martin L.J.
        • Toquet C.S.
        • et al.
        Restoration of the integrity of rat caeco-colonic mucosa by resistant starch, but not by fructo-oligosaccharides, in dextran sulphate sodium-induced experimental colitis.
        Br J Nutr. 2003; 90: 75-85
        • Rodriguez-Cabezas M.E.
        • Galvez J.
        • Lorente M.D.
        • et al.
        Dietary fiber down-regulates Colonia tumor necrosis factor α in trinitrobenzenesulfonic acid-induced Colitic rats.
        J Nutr. 2002; 132: 3263-3271
        • Cherbut C.
        • Michel C.
        • Lecannu G.
        The prebiotic characteristics of fructooligosaccharides are necessary for reduction of TNBS-induced colitis in rats.
        J Nutr. 2003; 133: 21-27
        • Newburg D.S.
        Oligosaccharides in human milk and bacterial colonization.
        J Pediatr Gastroenterol Nutr. 2000; 30: S8-S17
        • Faure M.
        • Moennoz D.
        • Mettraux C.
        • et al.
        The chronic colitis developed by HLA-B27 transgenic rats is associated with altered in vivo mucin synthesis.
        Dig Dis Sci. 2004; 49: 339-346
        • Faure M.
        • Moënoz D.
        • Montignon F.
        • et al.
        Mucin production and composition is altered in dextran sulfate sodium-induced colitis rats.
        Dig Dis Sci. 2003; 48: 1366-1373
        • Renes I.B.
        • Boshuizen J.A.
        • Van Nispen D.J.
        • et al.
        Alterations in Muc2 biosynthesis and secretion during dextran sulfate sodium-induced colitis.
        Am J Physiol Gastrointest Liver Physiol. 2001; 282: G382-G389
        • Bode L.
        • Kunz C.
        • Muhly Reinholz M.
        • et al.
        Inhibition of monocyte, lymphocyte and neutrophil adhesion to endothelial cells by human milk oligosaccharides.
        Thromb Haemost. 2004; 92: 1402-1410