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Prebiotics, Pediatric


Basics


Description


  • Prebiotics are nondigestible carbohydrates that promote growth of favorable intestinal microbiotia (probiotic microorganisms) by selective fermentation. Prebiotics may occur naturally or may be manufactured. Naturally occurring prebiotics include human milk oligosaccharides; many are substrates for bifidobacteria. Manufactured prebiotics that mimic this effect are therefore called "bifidogenic. " 
  • The following manufactured nondigestible carbohydrates were shown to be bifidogenic when added to standard infant formula:
    • Galacto-oligosaccharides (GOS) and long-chain fructo-oligosaccharides (lc-FOS from plants or sucrose); also called fructans
    • Some prebiotics are found in foods including chicory, cereals, agave, and milk, although may not be present in levels that would result in fermentation and a change in host microbiota. Additional processing or synthesis is required in these to achieve prebiotic activity.
    • Candidate prebiotics include lactulose, polysaccharides, oligosaccharides, and polyols.

Pathophysiology


  • Prebiotics such as FOS and GOS are selectively fermented resulting in a change in the composition or activity of the microbiota. Fermentation in colon ¢ † ’ increased bacteria ¢ † ’ increased water binding ¢ † ’ increased stool weight ¢ † ’ softer stools ¢ † ’ increased stool frequency. Butyrate may increase peristalsis, decrease intestinal transit time and reduce bloating, flatulence, and constipation.
  • Prebiotics may impact the immune system directly.
  • In vitro studies
    • Proposed mechanisms of indirect prebiotic action include gas and short-chain fatty acid production, pH changes, and promotion of fecal bacterial growth. Direct effects include binding of the prebiotic to microbe receptors.
  • Animal studies
    • Prebiotics exert their effects by enhancing intestinal barrier function. They also promote the growth of ileal lactobacilli through the production of lactic acid and decreasing intestinal pH.
    • Prebiotics increase calcium, magnesium, and iron absorption; growth; and bone mass in rats and pigs.
  • Clinical studies
    • Prebiotics exert their effects in the colon. They must retain the ability to be active through intestinal transit and changes in gastrointestinal pH. Most prebiotics interact with bifidobacteria and lactobacilli without altering other bacteria.
    • Stool bulk and intestinal transit time are frequently measured clinical markers of prebiotic effect.
    • Immune function including cytokine levels and antibody function are biomarkers that are measured to assess prebiotic effect.
    • FOS and long-chain inulin (50/50) increased bone mineral density and content in adolescents.
  • Clinical studies on effectivity
    • Variability in subjects including age, nutrition, and health status must be considered when interpreting results.
    • Reduced symptoms, decreased infections, and enhanced immune responses are health outcomes measured in clinical studies with prebiotics.
    • Human feeding trials to assess change in microbiota optimally monitor response to prebiotic intake.
  • Challenges to applying clinical studies in clinical practice
    • The body of evidence on some clinical effects is highly variable.
    • Prebiotic effects are specific to a particular product or combination of products.
    • Prebiotic effects are modulated by resident flora and by direct effects on the immune system
    • Effects depend on base line, on host: Pooling results is difficult.

Treatment


Dosing


  • Optimal prebiotic intake ranges from 2 to 20 g per day, depending on desired effect and prebiotic ingredient.
  • Prebiotic ingredients may be added to or be contained in cereals, breads, yogurts, sauces, and drinks.
  • Regular intake of prebiotic or prebiotic-containing foods is necessary for sustained effect.
  • Prebiotic formulations
    • GOS
      • Not widely studied as single prebiotic
      • Major compound of prebiotic combination products
      • No known safety concerns
    • sc-FOS
      • Not widely studied as single prebiotic
      • Some safety concerns and questionable benefits
    • Sc-FOS:lc-FOS
      • Not widely studied combination
      • No safety concerns
    • GOS:lc-FOS (9:1)
      • Best studied prebiotic mixture
      • Initial safety concerns shown not to be relevant.
      • Long history of safe use; benefits questioned
    • GOS:sc-FOS (9:1)
      • Not widely studied as a prebiotic mixture
      • No safety concerns
    • GOS:polydextrose (PDX) (1:1)
      • Several studies with this prebiotic mixture
      • Initial safety concerns addressed.
      • Good history of safe use
  • Safety, growth, and tolerance
    • Adding prebiotics to infant formula may create an osmotic effect resulting in softer stools.
    • A theoretical risk for dehydration has not been observed with usual dosing.
    • Increased intake of prebiotics may result in bloating and diarrhea that resolves with decreased consumption.

Clinical Applications


  • Inflammatory bowel disease (IBD)
    • Consumption of the prebiotic fructan may reduce inflammatory markers in persons with IBD.
  • Irritable bowel syndrome (IBS)
    • Low-dose consumption of prebiotics may reduce symptoms of IBS.
  • Stool consistency
    • Consumption of infant formulas supplemented with bifidogenic prebiotics including GOS, fructans, and oligosaccharides may result in a microbiota and stooling pattern similar to that of infants who consume human milk.
  • Other effects
    • Daily prebiotic intake, especially of fructans, may reduce appetite, increase gut peptide levels, and improve glucose tolerance.
    • Changes in the microbiota were noted.

Additional Reading


  • Ashley ‚  C, Johnston ‚  WH, Harris ‚  CL, et al. Growth and tolerance of infants fed formula supplemented with polydextrose (PDX) and/or galactooligosaccharides (GOS): double-blind, randomized, controlled trial. Nutr J.  2012;11:38. doi:10.1186/1475-2891-11-38. ‚  [View Abstract]
  • Binns ‚  N. Probiotics, Prebiotics, and the Gut Microbiota. Brussels, Belgium: International Life Sciences Institute; 2013.
  • Holscher ‚  HD, Faust ‚  KL, Czerkies ‚  LA, et al. Effects of prebiotic-containing infant formula on gastrointestinal tolerance and fecal microbiota in a randomized controlled trial. JPEN J Parenter Enteral Nutr.  2012;36(1)(Suppl):95S " “105S. ‚  [View Abstract]
  • Mugambi ‚  MN, Musekiwa ‚  A, Lombard ‚  M, et al. Synbiotics, probiotics or prebiotics in infant formula for full term infants: a systematic review. Nutr J.  2012;11:81. doi:10.1186/1475-2891-11-81. ‚  [View Abstract]
  • Veereman-Wauters ‚  G, Staelens ‚  S, Van de Broek ‚  H, et al. Physiological and bifidogenic effects of prebiotic supplements in infant formulae. J Pediatr Gastroenterol Nutr.  2011;52(6):763 " “771. ‚  [View Abstract]
  • Westerbeek ‚  EA, Hensgens ‚  RL, Mihatsch ‚  WA, et al. The effect of neutral and acidic oligosaccharides on stool viscosity, stool frequency and stool pH in preterm infants. Acta Paediatr.  2011;100(11):1426 " “1431. ‚  [View Abstract]
  • Xia ‚  Q, Williams ‚  T, Hustead ‚  D, et al. Quantitative analysis of intestinal bacterial populations from term infants fed formula supplemented with fructo-oligosaccharides. J Pediatr Gastroenterol Nutr.  2012;55(3):314 " “320. ‚  [View Abstract]

FAQ


  • Q: What is the difference between prebiotics and probiotics?
  • A: Probiotics are external microorganisms that are consumed to result in a health benefit. Prebiotics have actions that complement those of probiotics but are separate from those of probiotics. A prebiotic is fermented, stimulating the growth and activity of microorganisms, resulting in a health benefit.
  • Q: What are synbiotics?
  • A: Synbiotics are combinations of the beneficial effects of prebiotics and probiotics. The probiotic organism may play a role in the fermentation of the prebiotic. The probiotic may in turn create a more favorable environment for the proliferation of the probiotic.
  • Q: Where can I buy prebiotics?
  • A: Naturally occurring prebiotics occur in foods such as chicory, cereals, agave, and milk. However, prebiotic intake may be optimized by consuming foods with labels that indicate that the food contains FOS, inulin (a type of FOS), GOS, or TOS (transgalacto-oligosaccharides).
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