Background Fructans, such as inulin, are dietary fibers which stimulate gastro-intestinal (GI) function acting as prebiotics. Lipopolysaccharide (LPS) impairs GI motility, through production of reactive oxygen species. The antioxidant activity of various fructans was tested and the protective effect of inulin on colonic smooth muscle cell (SMC) impairment, induced by exposure of human mucosa to LPS, was assessed in an ex vivo experimental model. Methods The antioxidant capacity of fructans was measured in an in vitro system that simulates cooking and digestion processes. Human colonic mucosa and submucosa, obtained from disease-free margins of resected segments for cancer, were sealed between two chambers, with the mucosal side facing upwards with Krebs solution with or without purified LPS from a pathogenic strain of Escherichia coli (O111:B4) and inulin (Frutafit IQ), and the submucosal side facing downwards into Krebs solution. The solutions on the submucosal side were collected following mucosal exposure to Krebs in the absence (N-undernatant) or presence of LPS (LPS-undernatant) or LPS+inulin (LPS+INU-undernatant). Undernatants were tested for their antioxidant activity and the effects on SMCs contractility. Inulin protective effects on mucosa and submucosa layers were assessed measuring the protein oxidation level in the experimental conditions analyzed. Results Antioxidant activity of inulin, which was significantly higher compared to simple sugars, remained unaltered despite cooking and digestion processes. Inulin protected the mucosal and submucosal layers against protein oxidation. Following exposure to LPS-undernatant, a significant decrease in maximal acetylcholine (Ach)-induced contraction was observed when compared to the contraction induced in cells incubated with the N-undernatant (4±1% vs 25±5% respectively, P<0.005) and this effect was completely prevented by pre-incubation of LPS with Inulin (35±5%). Conclusions Inulin protects the human colon mucosa from LPS-induced damage and this effect appears to be related to the protective effect of inulin against LPS-induced oxidative stress.
References
[1]
Khan WI, Collins SM (2006) Gut motor function: immunological control inenteric infection and inflammation. Clin Exp Immun 143: 389–397. doi: 10.1111/j.1365-2249.2005.02979.x
[2]
De Winter BY, De Man JG (2010) Interplay between inflammation, immune system and neuronal pathways: effect on gastrointestinal motility. World J Gastroenterol 16: 5523–35. doi: 10.3748/wjg.v16.i44.5523
[3]
Barbara G, De Giorgio R, Stanghellini V, Cremon C, Salvioli B, et al. (2004) New pathophysiological mechanisms in irritable bowel syndrome. Aliment Pharm Ther 20: 1–9. doi: 10.1111/j.1365-2036.2004.02036.x
[4]
Lakhan SE, Kirchgessner A (2010) Neuroinflammation in inflammatory bowel disease. J Neuroinflammation 7: 37. doi: 10.1186/1742-2094-7-37
[5]
Bercík P, Wang L, Verdú EF, Mao YK, Blennerhassett P, et al. (2004) Visceral hyperalgesia and intestinal dysmotility in a mouse model of postinfective gut dysfunction. Gastroenterology 127: 179–87. doi: 10.1053/j.gastro.2004.04.006
[6]
Cullen JJ, Mercer D, Hinkhouse M, Ephgrave KS, Conklin JL (1999) Effects of endotoxin on regulation of intestinal smooth muscle nitric oxide synthase and intestinal transit. Surgery 125: 399–44. doi: 10.1016/s0039-6060(99)70246-1
[7]
Guarino MP, Sessa R, Altomare A, Cocca S, Di Pietro M, et al. (2013) Human colonic myogenic dysfunction induced by mucosal lipopolysaccharide translocation and oxidative stress. Dig Liver Dis 45: 1011–6. doi: 10.1016/j.dld.2013.06.001
[8]
Sansonetti PJ (2011) To be or not to be a pathogen: that is the mucosally relevant question. Mucosal Immunol 4(1): 8–14. doi: 10.1038/mi.2010.77
[9]
Lozupone CA, Stombaugh JI, Gordon JI, Jansson JK, Knight R (2012) Diversity, stability and resilience of the human gut microbiota. Nature 489: 220–30. doi: 10.1038/nature11550
[10]
Guarino MP, Altomare A, Stasi E, Marignani M, Severi C, et al. (2008) Effect of acute mucosal exposure to Lactobacillus rhamnosus GG on human colonic smooth muscle cells. J Clin Gastroenterol 42: S185–90. doi: 10.1097/mcg.0b013e31817e1cac
[11]
Ammoscato F, Scirocco A, Altomare A, Matarrese P, Petitta C, et al. (2013) Lactobacillus rhamnosus protects human colonic muscle from pathogen lipopolysaccharide-induced damage. Neurogastroenterol Motil 25(12): 984–e777. doi: 10.1111/nmo.12232
[12]
Rishi P, Mavi SK, Bharrhan S, Shukla G, Tewari R (2009) Protective efficacy of probiotic alone or in conjunction with a prebiotic in Salmonella-induced liver damage. FEMS Microbiol Ecol 69(2): 222–30. doi: 10.1111/j.1574-6941.2009.00703.x
[13]
Guarner F (2005) Inulin and oligofructose: impact on intestinal diseases and disorders. Br J Nutr 93: S61–5. doi: 10.1079/bjn20041345
[14]
Gibson GR, Roberfroid MB (1995) Dietary modulation of the human colonic microbiota: introducing the concept of prebiotics. J Nutr 125: 1401–1412.
[15]
Roberfroid M (2007) Prebiotics: the concept revisited. J Nutr 137: 830S–837S.
[16]
Kelly G (2008) Inulin-type prebiotics - a review: part 1. Altern Med Rev 13: 315–29.
[17]
Euler AR, Mitchell DK, Kline R, Pickering LK (2005) Prebiotic effect of fructo-oligosaccharide supplemented term infant formula at two concentrations compared with unsupplemented formula and human milk. J Pediatr Gastroenterol Nutr 40: 157–164. doi: 10.1097/00005176-200502000-00014
[18]
Bouhnik Y, Achour L, Paineau D, Riottot M, Attar A, et al. (2007) Four-week short chain fructo-oligosaccharides ingestion leads to increasing fecal Bifidobacteria and cholesterol excretion in healthy elderly volunteers. Nutr J 5: 6–42. doi: 10.1186/1475-2891-6-42
[19]
Bouhnik Y, Flourie B, Riottot M, Bisetti N, Gailing MF, et al. (1996) Effects of fructo-oligosaccharides ingestion on fecal Bifidobacteria and selected metabolic indexes of colon carcinogenesis in healthy humans. Nutr Cancer 26: 21–29. doi: 10.1080/01635589609514459
[20]
Buddington RK, Williams CH, Chen SC, Witherly SA (1996) Dietary supplement of neosugar alters the fecal flora and decreases activities of some reductive enzymes in human subjects. Am J Clin Nutr 63: 709–716.
[21]
Hidaka H, Tashiro Y, Eida T (1991) Proliferation of Bifidobacteria by oligosaccharides and their useful effect on human health. Bifidobacteria Microflora 10: 65–79.
[22]
Kelly G (2009) Inulin-type prebiotics: a review (Part 2). Altern Med Rev 14: 36–55.
[23]
Munjal U, Glei M, Pool-Zobel BL, Scharlau D (2009) Fermentation products of inulin-type fructans reduce proliferation and induce apoptosis in human colon tumour cells of different stages of carcinogenesis. Br J Nutr 102: 663–71. doi: 10.1017/s0007114509274770
[24]
Hague A, Elder DJ, Hicks DJ, Paraskeva C (1995) Apoptosis in colorectal tumour cells: induction by the short chain fatty acids butyrate, propionate and acetate and by the bile salt deoxycholate. Int J Cancer 60: 400–406. doi: 10.1002/ijc.2910600322
[25]
Livingston DP III, Hincha DK, Heyer AG (2009) Fructan and its relationship to abiotic stress tolerance in plants. Cell Mol Life Sci 66: 2007–2023. doi: 10.1007/s00018-009-0002-x
[26]
Mellado-Mojica E, Lòpez MG (2012) Fructan metabolism in A. tequilana Weber Blue variety along its developmental cycle in the field. J Agric Food Chem 60: 11704–11713. doi: 10.1021/jf303332n
[27]
ávila-Fernández A, Galicia-Lagunas N, Rodríguez-Alegría ME, Olvera C, López-Munguía A (2011) Production of functional oligosaccharides through limited acid hydrolysis of agave fructans. Food Chem 129: 380–386. doi: 10.1016/j.foodchem.2011.04.088
[28]
Arrizon J, Morel S, Gschaedler A, Monsan P (2010) Comparison of the water-soluble carbohydrate composition and fructan structures of Agave tequilana plants of different ages. Food Chem 122: 123–130. doi: 10.1016/j.foodchem.2010.02.028
[29]
Serpen A, Gokmen V, Pellegrini N, Fogliano V (2008) Direct measurement of the total antioxidant capacity of cereal products. J Cereal Sci 48: 816–820. doi: 10.1016/j.jcs.2008.06.002
[30]
Re R, Pellegrini N, Proteggente A, Pannala A. Min Yang M, et al. (1999) Antioxidant Activity applying an improved ABTS Radical Cation Decolorization Assay. Free Radic Biol Med 26: 1231–1237. doi: 10.1016/s0891-5849(98)00315-3
[31]
Sayar S, Jannink JL, White PJ (2005) In vitro bile acid binding of flours from oat lines varying in percentage and molecular weight distribution of β-glucan. J Agric Food Chem 53: 8797–8803. doi: 10.1021/jf051380g
[32]
Cao W, Fiocchi C, Pricolo VE (2005) Production of IL-1beta, hydrogen peroxide, and nitric oxide by colonic mucosa decreases sigmoid smooth muscle contractility in ulcerative colitis. Am J Physiol Cell Physiol 289: C1408–16. doi: 10.1152/ajpcell.00073.2005
[33]
Levine RL, Williams JA, Stadtman EP, Shacter E (1994) Carbonyl assays for determination of oxidatively modified proteins. Meth Enzymol 233: 346–357. doi: 10.1016/s0076-6879(94)33040-9
[34]
Tattoli I, Corleto VD, Taffuri M, Campanini N, Rindi G, et al. (2004) Optimisation of isolation of richly pure and homogeneous primary human colonic smooth muscle cells. Dig Liver Dis 36: 735–43. doi: 10.1016/j.dld.2004.06.016
[35]
Cullen JJ, Mercer D, Hinkhouse M, Ephgrave KS, Conklin JL (1999) Effects of endotoxin on regulation of intestinal smooth muscle nitric oxide synthase and intestinal transit. Surgery 125: 399–44. doi: 10.1016/s0039-6060(99)70246-1
[36]
Takakura K, Hasegawa K, Goto Y, Muramatsu I (1997) Nitric oxide produced by inducible nitric oxide synthase delays gastric emptying in lipopolysaccharide treated rats. Anaesthesiology 87: 652–7. doi: 10.1097/00000542-199709000-00027
[37]
Wechsung E (1996) The involvement of prostaglandins in the inhibiting effect of endotoxin on the myoelectric activity of the gastrointestinal system in pigs. Verh K Acad Geneeskd Belg 58: 711–38.
[38]
Fioramonti J, Bueno L, Du C (1984) Alterations of digestive motility by Escherichia coli endotoxin in rabbits mediated through central opiate receptors. In: Roman C, ed. Gastrointestinal Motility Lancaster: MPT Press Ltd. p 549–56.
[39]
Rebollar E, Arruebo MP, Plaza MA, Murillo MD (2002) Effect of lipopolysaccharide on rabbit small intestine muscle contractility in vitro: role of prostaglandins. Neurogastroenterol Motil 14: 633–642. doi: 10.1046/j.1365-2982.2002.00364.x
[40]
Shi XZ, Lindholm PF, Sarna SK (2003) NF-kappa B activation by oxidative stress and inflammation suppresses contractility in colonic circular smooth muscle cells. Gastroenterology 124: 1369–80. doi: 10.1016/s0016-5085(03)00263-4
[41]
De Winter BY, van Nassauw L, de Man JG, de Jonge F, Bredenoord AJ, et al. (2005) Role of oxidative stress in the pathogenesis of septic ileus in mice. Neurogastroenterol Motil 17: 251–61. doi: 10.1111/j.1365-2982.2004.00618.x
[42]
Rebollar E, Arruebo MP, Plaza MA, Murillo MD (2002) Effect of lipopolysaccharide on rabbit small intestine muscle contractility in vitro: role of prostaglandins. Neurogastroenterol Motil 14: 633–42. doi: 10.1046/j.1365-2982.2002.00364.x
[43]
Stoyanova S, Geuns J, Hideg E, Van Den Ende W (2011) The food additives inulin and stevioside counteract oxidative stress. Int J Food Sci Nutr 62(3): 207–14. doi: 10.3109/09637486.2010.523416
[44]
Van den Ende W, Peshev D, De Gara L (2011) Disease prevention by natural antioxidants and prebiotics as ROS scavengers in the gastro-intestinal tract. Trends Food Sci Tech 22: 689–697. doi: 10.1016/j.tifs.2011.07.005
[45]
Busserolles J, Gueux E, Rock E, Demigne C, Mazur A, et al. (2003) Oligofructose protects against the hypertriglyceridemic and pro-oxidative effects of a high fructose diet in rats. J Nutr 133: 1903–1908.
[46]
Li XM, Shi YH, Wang F, Wang HS, Le GW (2007) In vitro free radical scavenging activities and effect of synthetic oligosaccharides on antioxidant enzymes and lipid peroxidation in aged mice. J Pharm Biomed Anal 43: 364–370. doi: 10.1016/j.jpba.2006.06.041
[47]
Kroyer G (2010) Stevioside and Stevia-sweetener in food: Application, stability and interaction with food ingredients. J Verbr Lebensm 5: 225–229. doi: 10.1007/s00003-010-0557-3
[48]
Han JS, Kozukue N, Young KS, Lee KR, Friedman M (2004) Distribution of ascorbic acid in potato tubers and in home-processed and commercial potato foods. J Agric Food Chem 52: 6516–6521. doi: 10.1021/jf0493270
[49]
Locato V, Cimini S, De Gara L (2013) Strategies to increase Vitamin C in plants: from plant defense perspective to food biofortification. Front Plant Sci 4: 152 doi:10.3389/fpls.2013.00152.
[50]
Alles MS, Hautvast JG, Nagengast FM, Hartemink R, Van Laere KM, et al. (1996) Fate of fructo-oligosaccharides in the human intestine. Br J Nutr 76: 211–221. doi: 10.1079/bjn19960026
[51]
Rumessen JJ, Bode S, Hamberg O, Gudmand-Hoyer E (1990) Fructans of Jerusalem artichokes: intestinal transport, absorption, fermentation, and influence on blood glucose, insulin, and C-peptide responses in healthy subjects. Am J Clin Nutr 52: 675–681.
[52]
van de Wiele T, Boon N, Possemiers S, Jacobs H, Verstraete W (2007) Inulin-type fructans of longer degree of polymerization exert more pronounced in vitro prebiotic effects. J Appl Microbiol 102: 452–460. doi: 10.1111/j.1365-2672.2006.03084.x
