Probiotics new generation in pediatrics <br />Carlos D. Ramos-Perea M.D. F.A.A.P<br />Catedrático Asociado Escuelas de Medicina Ponce y Central del Caribe <br />Pediatra- Neonatólogo- Cuidados Intensivos<br />HOSPITAL MATERNO-INFANTIL SAN ANTONIO MAYAGUEZ, P.R.<br />
Objectives <br /><ul><li>Describe how the intestinal microflora support development of healthy immune system.
Understand factors that affect bacterial colonization of the intestinal tract.
Review data supporting clinical benefits of probiotics particularly bifidobacteria and that is safe and well tolerated by infants and children.
GOOD START REVIEW</li></li></ul><li>Facts about Probiotics<br /><ul><li>Prebiotics: Non digestible food ingredients that selectively stimulate the growth or activity of limited number of bacteria in the colon that have the potential to improve host health.
Non pathogenic microoranism resistant to acid & bile that can, adhere to epithelial tissue, transiently colonize GI, produce antimicrobial, modulate immune response and influence metabolic activity of intestinal flora.</li></li></ul><li>
Cont. facts about probiotics<br /><ul><li>Beneficial effects of probiotics are strain specific and dose dependant relationship; has been suggested.
BIFIDOBACTERIA AND LACTOBACILLI are the most commonly studied genera of all probiotics.</li></li></ul><li>Cont. facts about probiotics<br /><ul><li>Lactic acid bacteria convert sugars(lactose) and other CHO into lactic acid.
PH gets lower, and creates poor environment for growth.
Lactobacillus contains lactase within their cell wall, adhering to the intestinal microvillus, digesting lactose.
Non fermented milk containing L.bulgaricus significantly reduced both breath hydrogen results and symptoms of lactose int.</li></ul> De verse et all am j clin nutr 2001:73<br />
Human Intestinal Flora (Microbiota)<br /><ul><li>More than 500 species
Produce short chain fatty acids: acetate and lactate
Survive intestinal digestion and appear in stool
Predominant flora of breast fed infants</li></ul>19<br />Bifidobacterium lactis<br />Nomenclature: B. lactis also: B. animalis sub-species lactis, also B. bifidum, strain Bb12<br />
Bifidobacteria Supplementation can Increase colonization with Bifidobacteria<br />20<br />Langhendries 1995<br />
Number of Scientific Publications on Probiotics<br />21<br />
Nestle research center<br /><ul><li>Found bacteria from mother gut are transferred via breast to infant gut.
Translocated bacteria influence colonization of infant bowel contribute to education of infant gut.
For MULTIPLE and VARIABLE reasons some infants can't breast feed. Research has proven that formula with probiotics provide the same flora as breast feed reducing allergies, infections and improve defenses.</li></li></ul><li>NRC CONTINUATION<br /><ul><li>Natural birth is not sterile and C/S neonates don't benefit from this inoculum.
Diet in early life is a mayor factor for this ecosystem.
Since breast milk is not sterile and contains among other species bifidobacteria. It contains also oligosaccharides that promote growth of bifidobacteria.</li></li></ul><li>Intestinal Flora and Feeding Type (%)<br />24<br />Formula fed<br />Breast fed<br />Harmsen 2000<br />
NRC CONT.<br /><ul><li>Intestinal flora is critical in the development of immune response.
80% of immunologically active cells are contained in the gut.(GALT)
Germ free animals revealed underdeveloped mucosal inmune system with very small PEYER patches,decreased lymphocytes in mucosa and absent IGA producing cells.
The signaling of bacteria through receptors in mucosa are responsible for development of immune system. </li></li></ul><li>Immune system cells-B and T cells adaptive response <br />
Antimicrobial activities of probiotics include the (1) production of bacteriocins/ defensins , (2) competitive inhibition with pathogenic bacteria, (3) inhibition of bacterial adherence translocation, and (4) reduction of luminal pH. Probiotics bacteria can also enhance intestinal barrier function by (5) increasing mucus production.<br />
(mechanical defense)<br />Mucus layer<br />Categorized depends on cytokine profile<br />Promote- eos recruitment<br />Encourage T cell prolif. And macrophage activ. Inflammatory defense<br />The balance between T lymph important role in modulating immune response<br />Over expression<br />proinflamatory<br />
Enhance mucosal resistance against GI infections.
Increase Th1 cytokine interferon g allergic response.
Increases in acetic acid and scfa similar to breast.
Improve fecal flora in preterm and LBW by increasing bifidobacteria.</li></li></ul><li>Immune response cont.<br /><ul><li>In healthy newborns a T h2 response predominates, and gut permeability is very high, predisposing to allergic responses.
A” healthy” microbial balance will promote Th1 responses and decrease Th2 decreasing allergic and atopic disease.
Bifidobacteria and lactobacilli given orally will modulate GALT toward a balance T helper response and stimulate production of I-1O all of them having roles in immune response.
Markedly enhance production of secretory IGA.</li></li></ul><li>Effects of probiotics documented on gut barrier and inmune response<br /><ul><li>Promote mucin production and compete with and inhibit growth of potential pathogens.
Decrease gut permeability and enhance natural killer cell activity, macrophage activation and phagocytosis.
Improve weight gain and tolerance to lactose containing formulas in neonates.
Decrease incidence , severity, and mortality due to NEC in VLBW infants.</li></li></ul><li>PRETERMS AND IUGR<br /><ul><li>Impaired neonatal T and B cells(lack of Th1 differentiation), PMNS decrease chemotactic and adhesion.
Immature microvillus with mucus deficiency and iga with permeability to macromolecules, microorganism and toxins. This starts NEC.
Antenatal steroids induces intestinal maturation and NEC</li></li></ul><li>PRETERMS AND IUGR<br /><ul><li>Breast milk protects against NEC.
Iga ,lysozyme, complement, macrophages, growth factors, PAF-ACETYLHYDROLASE, and production of anti inflammatory cytokines.
Pufa in breast milk modifies cytokine and endotoxic response in rat model.
Trophic feedings is of establish value in preterm nutritional management and has been shown not to increase NEC. Standard milk advance is associated with NEC.</li></li></ul><li>INFANTS BREAST FEED ARE 7-10 TIMES LESS LIKELY TO SUFFER NEC.<br />
Prophylactic Probiotics for Prevention of Necrotizing Enterocolitis in Very Low Birth Weight Newborns<br /><ul><li> Department of Pediatrics, Medical College Calcutta, 88, College Street, CALCUTA 700073, India.</li></ul>Our study showed that enteral administration of prophylactic probiotics in neonatal intensive care could significantly reduce morbidity due to necrotising enterocolitis in very low birth weight newborn. It also helps in establishing early full enteral feeding and reduces hospital stay.<br /><ul><li>journal of Tropical Pediatrics 2009 55(2):128-131; doi:10.1093/
Ibañez,20 La administración temprana de suplementos de probióticos en pretérminos de muy bajo peso al nacer podría disminuir el riesgo de padecer enterocolitis necrotizante</li></ul>Vicente Ibáñez Pradas. Servicio de Cirugía Pediátrica, Hospital General de Castellón. Castellón (España).<br /><ul><li>(Lin HC et all. PEDIATRICS;2005;115:1-4)</li></ul>SPAIN STUDY<br />USA STUDY<br />
Probiotics Eases Irritable Bowel Syndrome Symptoms<br /><ul><li>The nerves and muscles in the bowel appear to be extra sensitive. Muscles may contract too much. These contractions can cause cramping and diarrhea during or shortly after a meal. Or the nerves may react when the bowel stretches, causing cramping or pain.</li></ul>Immunologic signaling<br />
Secretory otitis media<br /><ul><li>University of Gothenburg, SWEDEN
60 children properly diagnosed, receive 2 sprays per nostril for 10 days with LACTOBACILUS rhamnosun compare with 60 with placebo.30 ptes.(50%) Showed clinical cure of the process vs. only one with placebo.
No side effects reported. No changes in cytokine pattern reported.</li></li></ul><li>?????<br />Recent evidence showed mark improvement with probiotics.(Journal of Gastroenterology 2005)<br />
Safety of probiotics<br /><ul><li>In general lactobacillus and bifidobacteria had a long history of food safety use in human population.
To date 70 clinical studies involving more than 4000 children and infants(term & preterm)consuming infant formula and food containing microbial ingredients with no reports of probiotics adverse side effects.
Specific strains of bacteria(bifidobacteria) have shown modulating effects on GALT to have immnoprotective and in particular protections from pathogens such as rotavirus.</li></li></ul><li>Safety of Bifidobacteria<br /><ul><li>Genus Bifidobacteria:
Help maintain a healthy balance of intestinal flora.</li></ul>54<br />GINI TRIAL<br />* Von Berg 2007<br />
Expertos Recomiendan Niveles Medios de LCPUFAs en la Leche Humana para Formulas Infantiles de Niños a Termino<br />% de Acidos Grasos<br />DHA ARA<br />~0.4 ~0.4<br />~0.35 ~0.7<br />~0.35 ~0.5<br /> 0.2 0.35<br />Grupo Expertos<br />British Nutrition Foundation (BNF; ‘92)<br />Food and Agriculture Organization World Health Organization (FAO/WHO; ‘94)<br />Expert Panel convened by NIH/ISSFAL (‘99)<br />Child Health Foundation, Germany (‘01)<br />
Composición de Fosfolípidos de Corteza Cerebral (% de ac grasos totales)<br />*<br />*<br />* p< 0.05<br />Farquharson Lancet 92<br />
Benefits of GOOD START NATURAL CULTURES<br />63<br />Less curd formation<br />Faster gastric emptying<br />Easy protein digestion<br />Greater stool softness<br />Potential for allergy prevention<br />A good balance of intestinal florasupports a healthy immune system<br />