Probiotics aremicro-organisms that confer health benefits to the host. There is a growing body of evidence documenting the immune-modulatory ability of probiotic bacteria. The need for probiotic formulations has been appreciated for the health benefits in “topping up your good bacteria” or indeed in an attempt to normalise the dysbiotic microbiota associated with immunopathology. This review will focus on the use of probiotics in clinical practice, particularly related to neonatal practice, including explanations of what they are and how they work. Evidence for the health benefits of consuming probiotic bacteria are examined in several clinical conditions. Lastlywe have tried to solve the debated question that “should probiotics be used as standard of care in neonatal practice?”
1. Probiotics are enterally administered live “good’micro-organisms that colonise the gastrointestinal tract tomodulate the functions of the innatemicrobial community and immune system.
2. Thismay result in significant health benefits; for example enteral probiotic supplementation significantly reduces both severe necrotising enterocolitis and all-causemortality in preterminfants.
3. There is a debate on routine enteral probiotic supplementation for all preterm infants. Others advise caution pending results fromlarge clinical trials designed to address issues regarding safety and efficacy in the smallest, most vulnerable newborn population.
4. Probioticsmay also reduce atopic eczema in high-risk infantswhen administered to themother during pregnancy and to the infant post-natally and improve feeding tolerance in neonates.
(FAO), F.a.A.O.o.t.U.N. Health and Nutritional Properties of Probiotics in Food including Powder Milkwith Live Lactic Acid Bacteria. 2001.
Teitelbaum JE, Walker WA. Nutritional impact of pre- and probiotics as protective gastrointestinal organisms. Annu Rev Nutr 2002;22:107–38.
Hammerman C, Bin-Nun A, Kaplan M. Germwarfare: probiotics in defense of the premature gut. Clin Perinatol 2004;31(3):489– 500.
Stratiki Z, Costalos C, Sevastiadou S, Kastanidou O, Skouroliakou M, Giakoumatou A, et al. The effect of a bifidobacter supplemented bovine milk on intestinal permeability of preterm infants. Early Hum Dev 2007;83(9):575–9.
Awad H, Mokhtar H, Imam SS, Gad GI, Hafez H, Aboushady N. Comparison between killed and living probiotic usage versus placebo for the prevention of necrotizing enterocolitis and sepsis in neonates. Pak J Biol Sci 2010;13(6):253–62.
Rouge C, Piloquet H, Butel MJ, Berger B, Rochat F, Ferraris L, et al. Oral supplementation with probiotics in very-low-birthweight preterm infants: a randomized, double-blind, placebocontrolled trial. Am J Clin Nutr 2009;89(6):1828–35.
Neu J. Neonatal necrotizing enterocolitis: an update. Acta Paediatr Suppl 2005;94(449):100–5.
Guarner F, Malagelada JR. Gut flora in health and disease. Lancet 2003;361(9356):512-9
Stark PL, Lee A. The microbial ecology of the large bowel of breast-fed and formula-fed infants during the first year of life. J Med Microbiol 1982;15(2):189-203.
Yoshioka H, Iseki K, Fujita K. Development and differences of intestinal flora in the neonatal period in breast-fed and bottle-fed infants. Pediatrics 1983;72(3):317–21.
Kleessen B, Bunke H, Tovar K, Noack J, Sawatzki G. Influence of two infant formulas and human milk on the development of the fecal flora of newborn infants. Acta Paediatr 1995; 84 (12): 1347–56.
Balmer SE, Wharton BA. Diet and fecal flora in the newborn: breast milk and infant formula. Arch Dis Child 1989;64(12): 1672–7.
Harmsen HM, Wildeboer-veloo AC, Raangs GC, Wagendorp AA, Klijn N, Bindels JG, et al. Analysis of intestinal flora development in breast-fed and formula-fed infants by usingmolecular identification and detection methods. J Pediatr Gastroenterol Nutr 2000;30(1):61–7.
Commane DM, Shortt CT, Silvi S, Cresci A, Hughes RM, Rowland IR. Effects of fermentation products of pro- and prebiotics on trans-epithelial electrical resistance in an in vitro model of the colon. Nutr Cancer 2005;51(1):102–9.
Falony G, Vlachou A, Verbrugghe K, De Vuyst L. Cross-feeding between Bifidobacteriumlongum BB536 and acetate-converting, butyrate-producing colon bacteria during growth on oligofructose. Appl Environ Microbiol 2006;72(12):7835–41.
Bjorksten B, Naaber P, Sepp E, Mikelsaar M. The intestinal microflora in allergic Estonian and Swedish 2-year-old children. Clin Exp Allergy 1999;29(3):342–6.
Hickey L, Jacobs SE, Garland SM; Pro Prems Study Group. Probiotics in neonatology. J Paediatr Child Health 2012;48(9):777-83.
Hooper LV, Midtvedt T, Gordon JI. How host-microbial interactions shape the nutrient environment of the mammalian intestine. Annu Rev Nutr 2002;22:283–307.
Turnbaugh PJ, Ley RE, Mahowald MA, Magrini V, Mardis ER, Gordon JI. An obesity-associated gutmicrobiome with increased capacity for energy harvest. Nature 2006;444(7122):1027–31.
Kamiya T, Wang L, Forsythe P, Goettsche G, Mao Y, Wang Y, et al. Inhibitory effects of Lactobacillus reuteri on visceral pain induced by colorectal distension in Sprague-Dawley rats. Gut 2006;55(2):191–6.
Eckburg PB, Bik EM, Bernstein CN, Purdom E, Sargent M, et al. Diversity of the human intestinal microbial flora. Science 2005;308(5728):1635–8.
Palmer C, Bik EM, Di Giulio DB, Relman DA, Brown PO. Development of the human infant intestinal microbiota. PLoS Biol 2007;5(7):e177.
Pietzak M. Bacterial colonization of the neonatal gut. J Pediatr Gastroenterol Nutr 2004; 38(4):389–91.
Seksik P, Sokol H, Lepage P, Vasquez N, Manichanh C, Mangin I, et al. Review article: the role of bacteria in onset and perpetuation of inflammatory bowel disease. Aliment Pharmacol The 2006;24(3):11-8.
Osborn DA, Sinn JK. Probiotics in infants for prevention of allergic disease and food hypersensitivity. Cochrane Database Syst. Rev. 2007;4: CD006475.
Schwiertz A, Gruhl B, Lobnitz M, Michel P, Radke M, Blaut M. Development of the intestinal bacterial composition in hospitalized preterminfants in comparison with breast-fed, fullterm infants. Pediatr Res 2003;54(3):393–9.
Cotton CM. Early, prolonged use of postnatal antibiotics increased the risk of necrotising enterocolitis. Arch Dis Child Educ Pract Ed 2010;95(3):94.
Wang Y, Hoenig JD, Malin KJ, Qamar S, Petrof EO, Sun J, et al. 16S rRNA gene-based analysis of fecalmicrobiota frompreterm infants with and without necrotizing enterocolitis. ISME J 2009;3(8):944–54.
Mshvildadze M, Neu J, Shuster J, Theriaque D, Li N, Mai V. Intestinal microbial ecology in premature infants assessed with non-culture-based techniques. J Pediatr 2010;156(1): 20–5.
Magne F, Abely M, Boyer F, Morville P, Pochart P, Suau A. Lowspecies diversity and high interindividual variability in faeces of preterminfants as revealed by sequences of 16S rRNA genes and PCR-temporal temperature gradient gel electrophoresis profiles. FEMSMicrobiol Ecol 2006;57(1):128–38.
Wang B, Mao YK, Diorio C, Pasyk M, Wu RY, Bienenstock J, et al. Luminal administration ex vivo of a live Lactobacillus speciesmoderatesmouse jejunalmotilitywithinminutes. FASEB J 2010;24(10):4078–88.
Ortiz-Andrellucchi A, Sánchez-Villegas A, Rodríguez-Gallego C, Lemes A, Molero T, Soria A, et al. Immunomodulatory effects of the intake of fermented milk with Lactobacillus casei DN114001 in lactating mothers and their children. Br J Nutr 2008; 100(4):834–45.
Prescott SL, Wickens K, Westcott L, Jung W, Currie H, Black PN, et al. Supplementation with Lactobacillus rhamnosus or Bifidobacterium lactis probiotics in pregnancy increases cord blood interferon-gamma and breast milk transforming growth factor-beta and immunoglobin A detection. Clin Exp Allergy 2008;38(10):1606–14.
Manzoni P, Rinaldi M, Cattani S, Pugni L, Romeo MG, Messner H, et al. Bovine lactoferrin supplementation for prevention of late-onset sepsis in very low-birth-weight neonates: a randomized trial. JAMA 2009;302(13):1421-8.
Alfaleh K, Anabrees J, Bassler D, Al-Kharfi T. Probiotics for prevention of necrotizing enterocolitis in preterm infants. Cochrane Database Syst Rev 2011 16;(3): CD005496
Deshpande G, Rao S, Patole S, Bulsara M. Updated metaanalysis of probiotics for preventing necrotizing enterocolitis in preterm neonates. Pediatrics 2010;125(5):921-30.
Alfaleh K, Anabrees J, Bassler D. Probiotics reduce the risk of necrotizing enterocolitis in preterm infants: a meta-analysis. Neonatology 2010;97(2):93-9.
Srinivasjois R, Rao S, Patole S. Prebiotic supplementation of formula in preterm neonates: a systematic review and metaanalysis of randomised controlled trials. Clin Nutr 2009;28(3):237-42.
Barclay AR, Stenson B, Simpson JH, Weaver LT, Wilson DC. Probiotics for necrotizing enterocolitis: a systematic review. J Pediatr Gastroenterol Nutr 2007;45(5):569–76.
Guthmann F, Kluthe C, Buhrer C. Probiotics for prevention of necrotising enterocolitis: an updated meta-analysis. Klin Padiatr 2010;222(5):284–90.
Bell MJ, Ternberg JL, Feigin RD, Keating JP, Marshall R, Barton L, et al. Neonatal necrotizing enterocolitis. Therapeutic decisions based upon clinical staging. Ann Surg 1978; 187(1):1-7.
Indrio F, Riezzo G, Raimondi F, Bisceglia M, Cavallo L, Francavilla R. The effects of probiotics on feeding tolerance, bowel habits, and gastrointestinalmotility in pretermnewborns. J Pediatr 2008;152(6):801–6.
Braga TD, da Silva GA, de Lira PI, deCarvalho Lima M. Efficacy of Bifidobacterium breve and Lactobacillus casei oral supplementation on necrotizing enterocolitis in very-low-birthweight preterm infants: a double-blind, randomized, controlled trial. Am J Clin Nutr 2011;93(1):81–6.
Mohan R, Koebnick C, Schildt J, Mueller M, Radke M, Blaut M. Effects of Bifidobacterium lactis Bb12 supplementation on body weight, fecal pH, acetate, lactate, calprotectin, and IgA in preterm infants. Pediatr Res 2008;64(4):418–22.
Manzoni P, Lista G, Gallo E, Marangione P, Priolo C, Fontana P, et al. Routine Lactobacillus rhamnosus GG administration in VLBWinfants: a retrospective, 6-year cohort study. Early Hum Dev 2011;87(Suppl1):S35–8.
Garland SM, Tobin JM, Pirotta M, Tabrizi SN, Opie G, Donath S, et al. The Pro Prems trial: investigating the effects of probiotics on late onset sepsis in very preterm infants. BMC Infect Dis 2011;11:210.
Pelucchi C, Chatenoud L, Turati F, Galeone C, Moja L, Bach JF, et al. Probiotics supplementation during pregnancy or infancy for the prevention of atopic dermatitis: a meta-analysis. Epidemiology 2012;23(3):402-14.
Deshpande GC, Rao SC, Keil AD, Patole SK. Evidence-based guidelines for use of probiotics in preterm neonates. BMCMed 2011;9:92.
Kukkonen K, Kuitunen M, Haahtela T, Korpela R, Poussa T, Savilahti E. High intestinal Ig A associates with reduced risk of IgE-associated allergic diseases. Pediatr Allergy Immunol 2010;21(1):67–73.
Penders J, Thijs C, van den Brandt PA, Kummeling I, Snijders B, Stelma F, et al. Gut microbiota composition and development of atopic manifestations in infancy: the KOALA Birth Cohort Study. Gut 2007;56(5):661–7.
Kalliomaki M, Salminen S, Arvilommi H, Kero P, Koskinen P, Isolauri E. Probiotics in primary prevention of atopic disease: a randomized placebo-controlled trial. Lancet 2001;357 (9262): 1076–9.
Osborn DA, Sinn JK. Probiotics in infants for prevention of allergic disease and food hypersensitivity. Cochrane Database Syst Rev 2007 17;(4):CD006474.
Mihatsch WA, Braegger CP, Decsi T, Kolacek S, Lanzinger H, Mayer B, et al. Critical systematic reviewof the level of evidence for routine use of probiotics for reduction of mortality and prevention of necrotizing enterocolitis and sepsis in preterm infants. Clin Nutr 2012;31(1):6-15.
Wang Q, Dong J, Zhu Y. Probiotic supplement reduces risk of necrotizing enterocolitis and mortality in preterm very low-birth-weight infants: an updated meta-analysis of 20 randomized, controlled trials. J Pediatr Surg 2012;47(1):241-8.
Millar M, Wilks M, Fleming P, Costeloe K. Should the use of probiotics in the preterm be routine? Arch Dis Child Fetal Neonatal Ed 2012;97(1):F70-4.
Thomas DW, Greer FR. Probiotics and prebiotics in pediatrics. Pediatrics 2010;126(6):1217–31.
Agostoni C, Buonocore G, Carnielli VP, De Curtis M, Darmaun D, Decsi T, et al. Enteral nutrient supply for preterm infants: commentary from the European Society of Paediatric Gastroenterology, Hepatology and Nutrition Committee on Nutrition. J Pediatr Gastroenterol Nutr 2010;50(1):85–91.