Background: Lamina propria Th2 cytokines, interleukin (IL)-4 and IL-13, stimulate goblet cell (GC) proliferation and MUC2 production, which protect the intestinal mucosa. Elemental enteral nutrition (EEN) reduces tissue IL-4 and impairs barrier function. Proanthocyanidins (PACs) stimulate oral mucin levels. We hypothesized that adding PAC to EEN would maintain Th2–without stimulating Th1–cytokines and preserve luminal MUC2 vs EEN alone. Materials and Methods: Seventy mice were randomized to 5 diet groups–standard chow, intragastric EEN, or EEN with lowPAC, midPAC (50 mg), or highPAC (100 mg PAC/kg BW)–for 5 days, starting 2 days after gastric cannulation. Ileal tissue was analyzed for histomorphology and the cytokines IL-4, IL-13, IL-1β, IL-6, and TNF-α by enzyme-linked immunosorbent assay. MUC2 was measured in intestinal washes. Results: EEN lowered IL-13 (P < .05) compared with standard chow, whereas IL-4 was not significant (P < .07). LowPAC and midPAC increased IL-13 (P < .05), whereas highPAC increased both IL-4 and IL-13 (P < .05) compared with EEN. All EEN diets reduced (P < .05) crypt depth compared with the chow group. Compared with standard chow, GC numbers and luminal MUC2 were reduced with EEN (P < .05). These effects were attenuated (P < .05) with midPAC and highPAC. No changes were observed in tissue Th1 cytokines. Conclusions: Adding PACs to EEN reverses impaired intestinal barrier function following EEN by improving the gut mucous layer and function through increased GC size and number as well as levels of MUC2 and ileal IL-4 and IL-13.
IsaacsKLLewisJDSandbornWJSandsBETarganSR. State of the art: IBD therapy and clinical trials in IBD. Inflamm Bowel Dis. 2005;11(suppl 1):S3-S12.
2.
MosenthalACXuDDeitchEA. Elemental and intravenous total parenteral nutrition diet-induced gut barrier failure is intestinal site specific and can be prevented by feeding nonfermentable fiber. Crit Care Med. 2002;30(2):396-402.
3.
KudskKGomezFKangWUenoC. Enteral feeding of a chemically defined diet preserves pulmonary immunity but not intestinal immunity: the role of lymphotoxin beta receptor. JPEN J Parenter Enteral Nutr. 2007;(6):477-481.
4.
WuYKudskKADeWittRCTolleyEALiJ. Route and type of nutrition influence IgA-mediating intestinal cytokines. Ann Surg. 1999;229(5):662-668.
GuamerF. Role of intestinal flora in health and disease. Nutr Hosp. 2007;22(suppl 2):14-19.
7.
JohanssonMEAmbortDPelaseyedT. Composition and functional role of the mucus layers in the intestine. Cell Mol Life Sci. 2011;68(22):3635-3641.
8.
ScalbertADéprezSMilaIAlbrechtAMHuneauJFRabotS. Proanthocyanidins and human health: systemic effects and local effects in the gut. Biofactors. 2000;13(1-4):115-120.
9.
HellstromJKTorronenARMattilaPH. Proanthocyanidins in common food products of plant origin. J Agric Food Chem. 2009;57(17): 7899-7906.
10.
ManachCScalbertAMorandCRemesyCJimenezL. Polyphenols: food sources and bioavailability. Am J Clin Nutr. 2004;79(5):727-747.
11.
ReedJDKruegerCGVestlingMM. MALDI-TOF mass spectrometry of oligomeric food polyphenols. Phytochemistry. 2005;66(18):2248-2263.
12.
ArtsICHollmanPC. Polyphenols and disease risk in epidemiologic studies. Am J Clin Nutr. 2005;81(1)(suppl):317S-325S.
13.
ManachCMazurAScalbertA. Polyphenols and prevention of cardiovascular diseases. Curr Opin Lipidol. 2005;16(1):77-84.
14.
ScalbertAManachCMorandCRemesyCJimenezL. Dietary polyphenols and the prevention of diseases. Crit Rev Food Sci Nutr. 2005;45(4):287-306.
15.
HagermanAEButlerLG. The specificity of proanthocyanidin-protein interactions. J Biol Chem. 1981;256(9):4494-4497.
16.
MehanshoHAnnDKButlerLGRoglerJCarlsonDM. Induction of proline-rich proteins in hamster salivary glands by isoproterenol treatment and an unusual growth inhibition by tannins. J Biol Chem. 1987;262(25):12344-12350.
17.
17. MehanshoHCarlsonDM. Induction of protein and glycoprotein synthesis in rat submandibular glands by isoproterenol. J Biol Chem. 1983; 258(10):6616-6620.
18.
GonthierMPDonovanJLTexierOFelginesCRemesyCScalbertA. Metabolism of dietary procyanidins in rats. Free Radic Biol Med. 2003;35(8):837-844.
19.
ReedJD. Nutritional toxicology of tannins and related polyphenols in forage legumes. J Anim Sci. 1995;73(5):1516-1528.
20.
CosPDe BruyneTHermansNApersSBergheDVVlietinckAJ. Proanthocyanidins in health care: current and new trends. Curr Med Chem. 2004;11(10):1345-1359.
21.
BergstromKSKissoon-SinghVGibsonDL. Muc2 protects against lethal infectious colitis by disassociating pathogenic and commensal bacteria from the colonic mucosa. PLoS Pathog. 2010;6(5):e1000902.
22.
YusufSNokAJAmehDAAdelaiyeABBalogunEO. Quantitative changes in gastric mucosal glycoproteins: effect of cholinergic agonist and vagal nerve stimulation in the rat. Neurogastroenterol Motil. 2004;16(5):613-619.
23.
FinkelmanFDShea-DonohueTGoldhillJ. Cytokine regulation of host defense against parasitic gastrointestinal nematodes: lessons from studies with rodent models. Annu Rev Immunol. 1997;15:505-533.
24.
FallonPGJolinHESmithP. IL-4 induces characteristic Th2 responses even in the combined absence of IL-5, IL-9, and IL-13. Immunity. 2002;17(1):7-17.
25.
McKenzieGJBancroftAGrencisRKMcKenzieAN. A distinct role for interleukin-13 in Th2-cell-mediated immune responses. Curr Biol. 1998;8(6):339-342.
26.
KnazeVZamora-RosRLuján-BarrosoL. Intake estimation of total and individual flavan-3-ols, proanthocyanidins and theaflavins, their food sources and determinants in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Br J Nutr. 2011:1-14.
27.
WangYChungSJSongWOChunOK. Estimation of daily proanthocyanidin intake and major food sources in the U.S. diet. J Nutr. 2011;141(3):447-452.
28.
KumeHOkazakiKYamajiTSasakiH. A newly designed enteral formula containing whey peptides and fermented milk product protects mice against concanavalin A–induced hepatitis by suppressing overproduction of inflammatory cytokines. Clin Nutr. 2012;31(2):283-289.
29.
BastaracheJAWareLBGirardTDWheelerAPRiceTW. Markers of inflammation and coagulation may be modulated by enteral feeding strategy. JPEN J Parenter Enteral Nutr. 2012;36:732-740.
30.
AydoganAKismetKKilicogluB. Effects of various enteral nutrition solutions on bacterial translocation and intestinal morphology during the postoperative period. Adv Ther. 2007;24(1):41-49.
31.
FelicianoRPSheaMPShanmuganayagamDKruegerCGHowellABReedJD. Comparison of isolated cranberry (Vaccinium macrocarpon Ait.) proanthocyanidins to catechin and procyanidins A2 and B2 for use as standards in the 4-(dimethylamino)cinnamaldehyde assay. J Agric Food Chem. 2012;60(18):4578-4585.
32.
SitrenHSHellerPABaileyLBCerdaJJ. Total parenteral nutrition in the mouse: development of a technique. JPEN J Parenter Enteral Nutr. 1983;7(6):582-586.
33.
Subcommittee on Laboratory Animal Nutrition, Committee on Animal Nutrition, Board on Agriculture, National Research Council. Nutrient Requirements of Laboratory Animals. 4th rev ed. Washington, DC: National Academies Press; 1995.
34.
SanoYGomezFHermsenJ. Parenteral nutrition induces organ specific alterations in polymeric immunoglobulin receptor levels. J Surg Res. 2008;149(2):236-242.
35.
AksoyNThorntonDJCorfieldAParaskevaCSheehanJK. A study of the intracellular and secreted forms of the MUC2 mucin from the PC/AA intestinal cell line. Glycobiology. 1999;9(7):739-746.
36.
AskerNAxelssonMAOlofssonSOHanssonGC. Dimerization of the human MUC2 mucin in the endoplasmic reticulum is followed by a N-glycosylation-dependent transfer of the mono- and dimers to the Golgi apparatus. J Biol Chem. 1998;273(30):18857-18863.
37.
AxelssonMAAskerNHanssonGC. O-glycosylated MUC2 monomer and dimer from LS 174T cells are water-soluble, whereas larger MUC2 species formed early during biosynthesis are insoluble and contain nonreducible intermolecular bonds. J Biol Chem. 1998;273(30):18864-18870.
38.
LarssonJMKarlssonHCrespoJG. Altered O-glycosylation profile of MUC2 mucin occurs in active ulcerative colitis and is associated with increased inflammation. Inflamm Bowel Dis. 2011;17(11):2299-2307.
39.
KajiuraTTakedaTSakataS. Change of intestinal microbiota with elemental diet and its impact on therapeutic effects in a murine model of chronic colitis. Dig Dis Sci. 2009;54(9):1892-1900.
40.
OuelletteAJSelstedME. Paneth cell defensins: endogenous peptide components of intestinal host defense. FASEB J. 1996;10(11):1280-1289.
41.
FukatsuKKudskKA. Nutrition and gut immunity. Surg Clin North Am. 2011;91(4):755-770, vii.
PierreJFHeneghanAFTsaoFH. Route and type of nutrition and surgical stress influence secretory phospholipase A2 secretion of the murine small intestine. JPEN J Parenter Enteral Nutr. 2011;35(6):748-756.
44.
LiJKudskKAGocinskiBDentDGlezerJLangkamp-HenkenB. Effects of parenteral and enteral nutrition on gut-associated lymphoid tissue. J Trauma. 1995;39(1):44-51.
45.
KingBLiJKudskK. A temporal study of TPN-induced changes in gut-associated lymphoid tissue and mucosal immunity. Arch Surg. 1997;132(12):1303-1309.
46.
DeprezSMilaIHuneauJFTomeDScalbertA. Transport of proanthocyanidin dimer, trimer, and polymer across monolayers of human intestinal epithelial Caco-2 cells. Antioxid Redox Signal. 2001;3(6):957-967.
47.
BabaSOsakabeNNatsumeMTeraoJ. Absorption and urinary excretion of procyanidin B2 [epicatechin-(4beta-8)-epicatechin] in rats. Free Radic Biol Med. 2002;33(1):142-148.
48.
DonovanJLManachCRiosLMorandCScalbertARemesyC. Procyanidins are not bioavailable in rats fed a single meal containing a grapeseed extract or the procyanidin dimer B3. Br J Nutr. 2002;87(4):299-306.
49.
WangYHYangXLWangL. Effects of proanthocyanidins from grape seed on treatment of recurrent ulcerative colitis in rats. Can J Physiol Pharmacol. 2010;88(9):888-898.
50.
LiXLCaiYQQinHWuYJ. Therapeutic effect and mechanism of proanthocyanidins from grape seeds in rats with TNBS-induced ulcerative colitis. Can J Physiol Pharmacol. 2008;86(12):841-849.
51.
YoshiokaYAkiyamaHNakanoM. Orally administered apple procyanidins protect against experimental inflammatory bowel disease in mice. Int Immunopharmacol. 2008;8(13-14):1802-1807.
52.
VidalSFrancisLGuyotS. The mouth-feel properties of grape and apple proanthocyanidins in a wine-like medium. J Sci Food Agriculture. 2003;83(6):564-573.
53.
HoldernessJHedgesJFDaughenbaughK. Response of gammadelta T Cells to plant-derived tannins. Crit Rev Immunol. 2008;28(5):377-402.
54.
SteenwinckelVLouahedJLemaireMM. IL-9 promotes IL-13-dependent paneth cell hyperplasia and up-regulation of innate immunity mediators in intestinal mucosa. J Immunol. 2009;182(8): 4737-4743.
55.
IwashitaJSatoYSugayaHTakahashiNSasakiHAbeT. mRNA of MUC2 is stimulated by IL-4, IL-13 or TNF-alpha through a mitogen-activated protein kinase pathway in human colon cancer cells. Immunol Cell Biol. 2003;81(4):275-282.
56.
WangYHGeBYangXL. Proanthocyanidins from grape seeds modulates the nuclear factor–kappa B signal transduction pathways in rats with TNBS-induced recurrent ulcerative colitis. Int Immunopharmacol. 2011;11(10):1620-1627.
57.
Meyer-HoffertUHornefMWHenriques-NormarkB. Secreted enteric antimicrobial activity localises to the mucus surface layer. Gut. 2008;57(6):764-771.
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