1. Probiotics & Prebiotics in Paediatrics Dr.Hamid Rahimi Subspecialist in Pediatric Infectious Diseases, Isfahan University of Medical Sciences

2. Agenda: 1. Definition 2. Mechanisms of Action 3. Probiotic effects, what does the evidences say

3. What are probiotics? Definition  Live microorganisms which when administered in adequate amounts confer a health benefit on the host Examples  Lactobacilli  Bifidobacteria  Streptococcus  S boulardii Joint FAO/WHO Expert Consultation 2001

4. Prebiotic: A nondigestible food ingredient that benefits the host by selectively stimulating the favorable growth and/or activity of 1 or more indigenous probiotic bacteria. –OS supplementation (GOS and/or FOS) –Inulin, Soybean Synbiotic: A product that contains both probiotics and prebiotics. –Evidence for synergy of a specific prebiotic for a probiotic in the product is not essential. Synbiotics may be separate supplements or may exist in functional foods as food additives.

5. Functional food: Any modified food or food ingredient that provides a health benefit beyond that ascribed to any specific nutrient/nutrients it contains. –It must remain a food, and it must demonstrate its effect in amounts normally expected to be consumed in the diet. –Benefits may include functions relevant to improving health and well-being and/or reduction of risk of disease.

6. How do probiotics work? Level 1 –Luminal effects Level 2 –Epithelial effects Level 3 –Immune effects Rijkers et al. J Nutr 2010;140:671S-676S Ewaschul & Madsen Function Food Rev 2009;2:29-41

7. How do probiotics work? Level 1 (luminal effects) –Competitive inhibition of adhesion of pathogens –Antimicrobial actions Production of organic acids Release of hydrogen peroxide Release of bacteriocins Reduction of luminal pH Rijkers et al. J Nutr 2010;140:671S-676S Ewaschul & Madsen Function Food Rev 2009;2:29-41

8. How do probiotics work? Level 2 (epithelial effects) –Enhanced barrier function through effects on intercellular tight junctions –Enhanced mucin production and secretion –Enhanced IgA secretion –Destruction of toxin receptors Rijkers et al. J Nutr 2010;140:671S-676S Ewaschul & Madsen Function Food Rev 2009;2:29-41

9. How do probiotics work? Level 3 (immune effects) –Modulation of cytokine production –Stimulation of innate immunity –Modulation of dendritic cell and monocyte function –Increased expression of Treg cells Rijkers et al. J Nutr 2010;140:671S-676S Ewaschul & Madsen Function Food Rev 2009;2:29-41

10. Facts.. 1.Higher rate of Infection in C/S babies 2.Higher Allergy prevalence in recent years

11. Hygiene Hypothesis Improved hygienic conditions ↓ Less microbial exposure during early childhood ↓ Slower post-natal maturation of the immune system ↓ Delayed development of the optimal balance between TH-1 and TH-2-like immune response Stachan BMJ, 1989

12. Normal Immune Function

13. Importance: early programming Balanced Th1 and Th2 ↓ Less Infection and Allergy later in life

14. Probiotics; What does evidences say?

15. Published RCTs & systematic reviews/meta-analyses on probiotics RCTs 644 Meta-analysis 73 Cochrane Collaboration (search date : January 2011)

16. ESPGHAN & AAP Positioning in Safety ESPGHANAAP Safe Administration of currently evaluated probiotic-supplememnted formula to healthy infants does not raise safety concerns with regard to growth and adverse effects. Addition of probiotics to powdered infant formulas has not been demonstrated to be harmful to healthy term infants.

18. Effective Modestly effective in –Treating acute viral gastroenteritis in healthy children –Preventing antibiotic-associated diarrhea in healthy children. There is some evidence that probiotics prevent NEC in very low birth weight infants (birth weight between 1000 and 1500 g), but more studies are needed.

19. Encouraging but require further confirmation For treatment of childhood H pylori gastritis, irritable bowel syndrome, chronic ulcerative colitis, and infantile colic, as well as in preventing childhood atopy, although encouraging, RCTs are preliminary and require further confirmation.

20. Probiotics have not been proven to be beneficial in treating or preventing human cancers or in treating children with Crohn disease.

21. Safety concerns There are also safety concerns with the use of probiotics in infants and children who are immunocompromised, chronically debilitated, or seriously ill with indwelling medical devices.

22. Addition of probiotics to powdered infant formulas has not been demonstrated to be harmful to healthy term infants. On the other hand, evidence of clinical efficacy for their addition is insufficient to recommend the routine use of these formulas. No RCTs have directly compared the health benefits of feeding human milk versus infant formula supplemented with probiotics.

23. Addition of oligosaccharides as prebiotics to infant formula is not unreasonable but lacks evidence demonstrating clinical efficacy at this time. Cost/benefit studies are also necessary to support their addition to infant formulas.

24. Important questions remain… Important questions remain in establishing the clinical applications for pro/prebiotics, including … –The optimal duration of probiotic administration –Preferred microbial dose and species –The long-term impact on the gut microflora –Whether there is significant biological benefit in the administration of probiotics during pregnancy and lactation –biological benefit derived from probiotic-containing infant formulas.

28. Dosage Duration How to Store How to use

30. Quality is also a major issue in using probiotics in clinical practice. Many probiotic preparations do not contain the number of viable CFUs stated on the label. www.ConsumerLab.com, an independent laboratory that performs quality control assessments of dietary supplements, recently found in an analysis of probiotic products that 5 of 19 brands analyzed did not contain the number of live organisms claimed on the label.

31. Continue breast feeding Limit antibiotic therapy

33. Thank You