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Oligofructose and experimental model of neonatal necrotising enterocolitis

Published online by Cambridge University Press:  09 March 2007

M.-J. Butel*
UFR des Sciences Pharmaceutiques et Biologiques, Laboratoire de Microbiologie, 4 avenue de l'Observatoire, Université René Descartes, F-75270 Paris Cedex, 06, France
A.-J. Waligora-Dupriet
UFR des Sciences Pharmaceutiques et Biologiques, Laboratoire de Microbiologie, 4 avenue de l'Observatoire, Université René Descartes, F-75270 Paris Cedex, 06, France
O. Szylit
Unité d'Ecologie et Physiologie du Système Digestif, Equipe Métabolites Bactériens et Santé, Institut National de la Recherche Agronomique, Jouy-en Josas, France
*Corresponding author: Dr M-J. Butel, tel + 33 (0) 1 53 73 99 11, fax + 33 0 (1) 53 73 99 23, email
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The gut of preterm neonates is colonised with a paucity of bacterial species originating more from the environment than from the mother. Furthermore, a delayed colonisation by bifidobacteria promotes colonisation by potentially pathogenic bacteria. This may contribute towards the development of neonatal necrotising enterocolitis (NEC). The physiopathology of NEC is still unclear but immaturity of the gut, enteral feeding and bacterial colonisation are all thought to be involved. None of the current preventive treatments are considered satisfactory. Modulating the autochthonous microflora by probiotics or prebiotics could be a more reliable approach to prevention. Using gnotobiotic quails as an experimental model of NEC we have shown that onset of intestinal lesions requires a combination of low endogenous lactase activity, lactose in diet, and colonisation by lactose-fermenting bacteria such as the clostridia. The protective role of bifidobacteria was demonstrated in this model through a decrease in clostridial populations and in butyric acid. Oligofructose dietary supplementation was shown to enhance this effect with an increase in the bifidobacterial level and consequently a greater decrease in clostridia. However, oligofructose was unable to promote a bifidobacterial acquisition when the microflora was initially deprived of this group. Nevertheless, oligofructose can act as an anti-infective agent and decrease the occurrence or severity of the lesions depending on the bacteria involved. According to these results and to the fact that oligosaccharides are a major component of breast milk, the addition of oligofructose in formula milks may be a nutritional approach to favouring colonisation by a beneficial flora.

Research Article
Copyright © The Nutrition Society 2002


Blakey, JL, Lubitz, L, Campbell, NT, Gillam, GL, Bishop, RF & Barnes, GL (1985) Enteric colonization in sporadic neonatal necrotizing enterocolitis. Journal of Pediatric Gastroenterology and Nutrition 4, 591595.Google Scholar
Bousseboua, H, Le Coz, Y, Dabard, J, Szylit, O, Raibaud, P, Popoff, MR & Ravisse, P (1989) Experimental cecitis in gnotobiotic quails monoassociated with Clostridium butyricum strains isolated from patients with neonatal necrotizing enterocolitis and from healthy newborns. Infection and Immunity 57, 932936.Google Scholar
Brand Miller, J, Bull, S, Miller, J & McVeagh, P (1994) The oligosaccharide composition of human milk: temporal and individual variations in monosaccharide components. Journal of Pediatric Gastroenterology and Nutrition 19, 371376.Google Scholar
Butel, MJ, Catala, I, Tessèdre, AC, Bensaada, M, Durao, J & Szylit, O (1998 a) Are all bacteria involved in neonatal necrotising enterocolitis responsible for? Proceedings of the 2nd World Congress on Anaerobic Bacteria and Infections, Nice, France 3–6. October 1998.Google Scholar
Butel, MJ, Roland, N, Hibert, A, Popot, F, Favre, A, Tessèdre, AC, Bensaada, M, Rimbault, A & Szylit, O (1998 b) Clostridial pathogenicity in experimental necrotising enterocolitis in gnotobiotic quails and protective role of bifidobacteria. Journal of Medical Microbiology 47, 391399.Google Scholar
Butel, MJ & Szylit, O (2000) Bifidobacteria in necrotizing enterocolitis. Gastroenterology 118, 12801281.Google Scholar
Butel, MJ, Trombert, S, Philippe, JC, Hoarau, C, Vodovar, M, Saliba, E, Magny, JF & Borderon, JC (1999) Implantation de la flore digestive chez le prématuré., 5 ème journées Francophones de Recherche en Néonatologie, Rouen, 16–18. December 1999.Google Scholar
Campbell, JM, Fahey, GC & Wolf, BW (1997) Selected indigestible oligosaccharides affect large bowel mass, cecal and fecal short-chain fatty acids, pH and microflora in rats. Journal of Nutrition 127, 130136.Google Scholar
Caplan, MS, Miller-Catchpole, R, Kaup, S, Russell, T, Lickerman, M, Amer, M, Xiao, Y & Thomson, R (1999) Bifidobacterial supplementation reduces the incidence of necrotizing enterocolitis in a neonatal rat model. Gastroenterology 117, 577583.Google Scholar
Cashore, WJ, Peter, G, Lauermann, M, Stonestreet, BS & Oh, W (1981) Clostridia colonization and clostridia toxin in neonatal necrotizing enterocolitis. Journal of Pediatrics 98, 308311.Google Scholar
Catala, I, Butel, MJ, Bensaada, M, Popot, F, Tessèdre, AC, Rimbault, A & Szylit, O (1999) Oligofructose contributes to the protective role of bifidobacteria in experimental necrotising enterocolitis in quails. Journal of Medical Microbiology 48, 8994.Google Scholar
Dai, D & Walker, WA (1998) Role of bacterial colonization in neonatal necrotizing enterocolitis and its prevention. Acta Padiatric Sinica 6, 357365.Google Scholar
Danan, C, Huret, Y, Bensaada, M, Szylit, O & Butel, MJ (2000) Could oligosaccharides supplementation promote gut colonization with a beneficial flora in pre-term infant? Journal of Pediatric Gastroenterology and Nutrition 30, 217219.Google Scholar
Delmée, M, Verellen, G, Avesani, V & Francois, G (1988) Clostridium difficile in neonates: serogrouping and epidemiology. European Journal of Pediatrics 147, 3640.Google Scholar
Ducluzeau, R (1990) L'etablissement de la flore du tractus gastro-intestinal chez le nouveau-né humain. Recherche en Gynécologie 2, 7175.Google Scholar
Finegold, S (1977) Anaerobic Bacteria in Human Disease. New York, NY: Academic Press.Google Scholar
Garleb, KA, Snook, JT, Marcon, MJ, Wolf, BW & Johnson, WA (1996) Effect of fructo-oligosaccharide containing enteral formulas on subjective tolerance factors, serum chemistry profiles, and faecal bifidobacteria in healthy adult male subjects. Microbial Ecology in Health and Disease 9, 279285.Google Scholar
Gewolb, IH, Schwalbe, RS, Taciak, VL, Harrison, TS & Panigrahi, P (1999) Stool microflora in extremely low birthweight infants. Arch.Dis.Child Fetal Neonatal Ed. 80, F167F173.Google Scholar
Gibson, GR, Beatty, ER, Wang, X & Cummings, JH (1995) Selective stimulation of bifidobacteria in the human colon by oligofructose and inulin. Gastroenterology 108, 975982.Google Scholar
Gibson, GR & Wang, X (1994) Enrichment of bifidobacteria from human gut contents by oligofructose using continuous culture. FEMS Microbiology Letters 118, 121128.Google Scholar
Gothefors, L & Blenkharn, I (1978) Clostridium butyricum and necrotizing enterocolitis. Lancet 5253.Google Scholar
Hilbrands, W & Streekstra, H (1996) New Biotechnological Ingredients for Infant Nutrition. pp. 3840. Maarsen, The Netherlands: Miller Freeman Plc.Google Scholar
Hodges, RD (1979) The digestive system. In Histology of the Fowl, pp. 8084 [Hodges, RD, editor]. London: Academic Press.Google Scholar
Howard, FM, Bradley, JM, Flynn, DM, Noone, P & Szawatkowski, M (1977) Outbreak of necrotizing enterocolitis caused by Clostridium butyricum. Lancet 10991102.Google Scholar
Howard, MD, Gordon, DT, Pace, LW, Garleb, KA & Kerley, MS (1995) Effects of dietary supplementation with fructooligosaccharides on colonic microbiota populations and epithelial cell proliferation in neonatal pigs. Journal of Pediatric Gastroenterology and Nutrition 21, 297303.Google Scholar
Kliegman, RM, Fanaroff, AA, Izant, R & Speck, WT (1979) Clostridia as pathogens in neonatal necrotizing enterocolitis. Journal of Pediatrics 95, 287289.Google Scholar
Kosloske, AM (1994) Epidemiology of necrotizing enterocolitis. Acta Paediatrica 396, Suppl., 27.Google Scholar
Kosloske, AM, Ulrich, JA & Hoffman, H (1978) Fulminant necrotising enterocolitis associated with clostridia. Lancet 2, 10141016.Google Scholar
Kuntz, C & Rudloff, S (1993) Biological functions of oligosaccharides in human milk. Acta Paediatrica 82, 903912.Google Scholar
Langhendries, JP, Paquay, T, Hannon, M & Darimont, J (1998) Acquisition de la flore intestinale néonatale: rôle sur la morbidité et perspectives thérapeutiques. Arch.Pediatr. 5, 644653.Google Scholar
Laverdière, M, Robert, A, Chicoine, R, Salet, D & Rosenfeld, R (1978) Clostridia in necrotising enterocolitis. Lancet 2, 377.Google Scholar
Lawrence, G, Bates, J & Gaul, A (1982) Pathogenesis of neonatal necrotising enterocolitis. Lancet 137139.Google Scholar
Loc, C, Larroche, JC, Paul, G & Beaudoin, M (1980) Infection à Clostridium perfringens et entérocolite ulcéro-nécrosante. Archives Françaises de Pédiatrie 37, 233240.Google Scholar
Neu, J (1996) Necrotizing enterocolitis. The search for a unifying pathogenic theory leading to prevention. Pediatric Clinics of North America 43, 409432.Google Scholar
Newburg, DS (1997) Do the binding properties of oligosaccharides in milk protect human infants from gastrointestinal bacteria? Journal of Nutrition 127, 980S984S.Google Scholar
Popoff, MR, Jolivet-reynaud, C & Carlier, JP (1987) Cytotoxic activity of Clostridium butyricum supernatants induced by butyrate. FEMS Microbiology Letters 43, 95100.Google Scholar
Sakata, H, Yoshioka, H & Fujita, K (1985) Development of the intestinal flora in very low birth weight infants compared to normal full-term newborns. European Journal of Pediatrics 144, 186190.Google Scholar
Speer, ME, Taber, LH, Yow, MD, Rudolph, AJ, Urteaga, J & Waller, S (1976) Fulminant neonatal sepsis and necrotizing enterocolitis associated with a ‘nonenteropathogenic’ strain of Escherichia coli. The Journal of Pediatrics 89, 9195.Google Scholar
Szylit, O, Butel, MJ & Rimbault, A (1997) An experimental model of necrotising enterocolitis. Lancet 350, 3334.Google Scholar
Wang, X & Gibson, GR (1993) Effects of the in vitro fermentation of oligofructose and inulin by bacteria growing in the human large intestine. Journal of Applied Bacteriology 75, 373380.Google Scholar
Westra-Meijer, CMM, Degener, JE, Dzoljic-danolovic, G, Michel, MF & Mettau, JW (1983) Quantitative study of the aerobic and anaerobic faecal flora in neonatal necrotising enterocolitis. Archives of Disease in Childhood 58, 523528.Google Scholar