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2. . . . DESARROLLO DE LA MICROBIOTA INTESTINAL. nacimiento. 4 d
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1. 1 PARADIGMAS DEL USO DE PROBIÓTICOS EN PEDIATRÍA Nenna Lung de Martínez MD.
Pediatra Nutrióloga
Pontificia U. Javeriana – U. El Bosque
2. 2 How does the intestinal flora develop?
The aseptic gastro-intestinal tract of the fetus is inoculated during birth by the mother’s intestinal and vaginal flora.
This leads to a diverse flora of bifidobacteria, enterobacteria, bacteroides, clostridia and gram-positive cocci.
After this first inoculation, the flora changes rapidly, presumably under the influence of the diet.
In entirely breast-fed infants, the flora is predominantly bifidobacteria, which is possibly caused by selective components that are present in human milk.
In contrast, the flora of formula-fed infants is more diverse and does not show the predominance of bifidobacteria.
The introduction of solid food leads to the bifidobacteria becoming less predominant in breast-fed infants.
At 12 months of age, the anaerobic bacterial population of the large bowel of breast-fed and formula-fed infants begin to resemble the microflora of adults in both number and composition.
References:
Stark PL, Lee A. J Med Microbiol 1982; 15(2):189-203
Orrhage K, Nord CE. Acta Paediatr 1999; suppl. 430:47-57
Harmsen H et al. J Pediatr Gastroenterol Nutr 2000; 30:61-67
How does the intestinal flora develop?
The aseptic gastro-intestinal tract of the fetus is inoculated during birth by the mother’s intestinal and vaginal flora.
This leads to a diverse flora of bifidobacteria, enterobacteria, bacteroides, clostridia and gram-positive cocci.
After this first inoculation, the flora changes rapidly, presumably under the influence of the diet.
In entirely breast-fed infants, the flora is predominantly bifidobacteria, which is possibly caused by selective components that are present in human milk.
In contrast, the flora of formula-fed infants is more diverse and does not show the predominance of bifidobacteria.
The introduction of solid food leads to the bifidobacteria becoming less predominant in breast-fed infants.
At 12 months of age, the anaerobic bacterial population of the large bowel of breast-fed and formula-fed infants begin to resemble the microflora of adults in both number and composition.
References:
Stark PL, Lee A. J Med Microbiol 1982; 15(2):189-203
Orrhage K, Nord CE. Acta Paediatr 1999; suppl. 430:47-57
Harmsen H et al. J Pediatr Gastroenterol Nutr 2000; 30:61-67
3. 3 Undigested components of the diet, such as resistant starch, pectin and non-digestible oligosaccharides, provide substrate for the colonic microflora.
These substances stimulate the growth and metabolism of the bacteria present, giving rise to several beneficial effects:-
synthesis of acids and a resultant reduction in pH,
promotion of enterocyte growth which strengthens the gut barrier,
stimulation of maturation of the immune system.
The overall beneficial effect of these changes is a reduction in colonisation of the colon by pathogenic microorganisms.Undigested components of the diet, such as resistant starch, pectin and non-digestible oligosaccharides, provide substrate for the colonic microflora.
These substances stimulate the growth and metabolism of the bacteria present, giving rise to several beneficial effects:-
synthesis of acids and a resultant reduction in pH,
promotion of enterocyte growth which strengthens the gut barrier,
stimulation of maturation of the immune system.
The overall beneficial effect of these changes is a reduction in colonisation of the colon by pathogenic microorganisms.
4. 4
5. 5 COLONIZACIÓN CUANTITATIVA DEL TRACTO GI. What does the quantitative colonisation of the GI-tract look like?
Due to the acidic pH in the stomach its colonisation with bacteria is low with numbers of 0 to 103 CFU per ml.
The small intestine constitutes a zone of transition between the sparsely populated stomach and the luxuriant bacterial flora of the colon.
The main factors limiting bacterial growth in the upper parts of the small bowel are rapid transit of the contents and the secretion of bile and pancreatic juice.
The highest bacterial counts are found in the colon with up to 1013 colony forming units (cfu) per ml gut content.
Reference:
Simon GL & Gorbach SL. Gastroenterol 1984; 86:174-193
What does the quantitative colonisation of the GI-tract look like?
Due to the acidic pH in the stomach its colonisation with bacteria is low with numbers of 0 to 103 CFU per ml.
The small intestine constitutes a zone of transition between the sparsely populated stomach and the luxuriant bacterial flora of the colon.
The main factors limiting bacterial growth in the upper parts of the small bowel are rapid transit of the contents and the secretion of bile and pancreatic juice.
The highest bacterial counts are found in the colon with up to 1013 colony forming units (cfu) per ml gut content.
Reference:
Simon GL & Gorbach SL. Gastroenterol 1984; 86:174-193
6. 6 Absorción de Nutrientes
7. 7 COMPOSICIÓN DE LA MICROBIOTA INTESTINAL The large intestine can be described as a complex microbial eco-system.
It has been recognised for many years that the different species of the intestinal flora may exert beneficial as well as harmful effects on health.
The potentially harmful effects comprise the production of pathogenic or toxic substances, potentially resulting in diarrhoea, constipation, liver damage, cancer, encephalopathy and gastro-intestinal putrefaction.
The beneficial effects include inhibiting the growth of exogenous and harmful bacteria, stimulation of immune functions, aiding the digestion and absorption of food ingredients and minerals, and the synthesis of vitamins.
Whereas some species might exert only harmful effects such as pseudomonas or clostridia, others may have harmful as well as beneficial effects such as E. coli and bacteroides.
However, there are also some groups which only have beneficial effects such as lactobacilli and bifidobacteria.
The central vertical axis indicates the approximate bacterial counts of different species in adults. Bacteroides and bifidobacteria are the most common species.
Reference:
Gibson GR, Roberfroid MB. J Nutr 1995; 125:1401-1412The large intestine can be described as a complex microbial eco-system.
It has been recognised for many years that the different species of the intestinal flora may exert beneficial as well as harmful effects on health.
The potentially harmful effects comprise the production of pathogenic or toxic substances, potentially resulting in diarrhoea, constipation, liver damage, cancer, encephalopathy and gastro-intestinal putrefaction.
The beneficial effects include inhibiting the growth of exogenous and harmful bacteria, stimulation of immune functions, aiding the digestion and absorption of food ingredients and minerals, and the synthesis of vitamins.
Whereas some species might exert only harmful effects such as pseudomonas or clostridia, others may have harmful as well as beneficial effects such as E. coli and bacteroides.
However, there are also some groups which only have beneficial effects such as lactobacilli and bifidobacteria.
The central vertical axis indicates the approximate bacterial counts of different species in adults. Bacteroides and bifidobacteria are the most common species.
Reference:
Gibson GR, Roberfroid MB. J Nutr 1995; 125:1401-1412
8. 8 ECOSISTEMA INTESTINAL Depende de:
Medio ambiente
Alimentación
Patrimonio genético
9. 9 FACTORES QUE AFECTAN LA MICROBIOTA INTESTINAL Extrínsecos:
Carga microbiana del medio ambiente
Hábitos alimentarios
Tipo de alimentos
Composición de la microflora materna
10. 10 MODULACIÓN NUTRICIONAL DE LA MICROBIOTA INTESTINAL
Prebiótico: aumentando el aporte de substratos utilizables por poblaciones endógenas.
Probiótico: aumentando el aporte de microorganismos exógenos.
11. 11 PROPIEDADES PROTECTORAS DEUNA MICROBIOTA DOMINADA POR BACILLUS CLAUSSI What is the relevance of the bifido-dominant flora in breast-fed infants?
Several health-promoting and protective properties have been attributed to bifidobacteria such as:
lowering the pH by production of acids such as acetic and lactic acids, leading to an antibacterial environment,
the inhibition of pathogens by the secretion of substances which directly inhibit many other bacteria,
activation of the immune system, as described before,
production of digestive enzymes such as casein phosphatase and lysozyme,
the production of vitamins, largely of the B-group.
The overall benefit of these effects is to protect infants from the growth of pathogenic micro-organisms in the intestine during a phase of insufficient immune response.
For these reasons, it seems very desirable to also increase the numbers of bifidobacteria in the intestinal flora of formula-fed infants.
References:
Gibson GR, Roberfroid M. J Nutr 1995; 1256:1401-1412
Koletzko B et al. Br J Nutr 1998; 80 (suppl1):S5-S45
Salminen S et al. Br J Nutr. 1998; 80 (suppl1):S147-S171
Kalliomäki M et al. J Allergy Clin Immunol 2001; 107:129-34
Björksten B et al. J Allergy Clin Immunol 2001; 108: 516-20What is the relevance of the bifido-dominant flora in breast-fed infants?
Several health-promoting and protective properties have been attributed to bifidobacteria such as:
lowering the pH by production of acids such as acetic and lactic acids, leading to an antibacterial environment,
the inhibition of pathogens by the secretion of substances which directly inhibit many other bacteria,
activation of the immune system, as described before,
production of digestive enzymes such as casein phosphatase and lysozyme,
the production of vitamins, largely of the B-group.
The overall benefit of these effects is to protect infants from the growth of pathogenic micro-organisms in the intestine during a phase of insufficient immune response.
For these reasons, it seems very desirable to also increase the numbers of bifidobacteria in the intestinal flora of formula-fed infants.
References:
Gibson GR, Roberfroid M. J Nutr 1995; 1256:1401-1412
Koletzko B et al. Br J Nutr 1998; 80 (suppl1):S5-S45
Salminen S et al. Br J Nutr. 1998; 80 (suppl1):S147-S171
Kalliomäki M et al. J Allergy Clin Immunol 2001; 107:129-34
Björksten B et al. J Allergy Clin Immunol 2001; 108: 516-20
12. 12
13. 13 PROBIÓTICOS Pre- and probiotic supplements are the only efficient methods available to increase the bifidogenicity of infant formulas.
What kind of substances are described as pro- and prebiotics?
A probiotic is defined as a live microbial food supplement, including fermented milk and over-the counter preparations that contain lyophilised bacteria, that beneficially affect the host by improving its intestinal microbial balance.
In other words, live beneficial microorganisms are administered, they remain in a viable form during transit through the gastrointestinal tract and become active on reaching the colon, where appropriate physiochemical conditions for their growth occur.
References:
Collins MD et al. Probiotics, prebiotics, and synbiotics: approaches for modulating the microbial ecology of the gut. Am J Clin Nutr 1999; 69:1052S-1057S
Fuller R. A review: probiotics in man and animals. J Appl Bacteriol 1989; 66:365-738
Pre- and probiotic supplements are the only efficient methods available to increase the bifidogenicity of infant formulas.
What kind of substances are described as pro- and prebiotics?
A probiotic is defined as a live microbial food supplement, including fermented milk and over-the counter preparations that contain lyophilised bacteria, that beneficially affect the host by improving its intestinal microbial balance.
In other words, live beneficial microorganisms are administered, they remain in a viable form during transit through the gastrointestinal tract and become active on reaching the colon, where appropriate physiochemical conditions for their growth occur.
References:
Collins MD et al. Probiotics, prebiotics, and synbiotics: approaches for modulating the microbial ecology of the gut. Am J Clin Nutr 1999; 69:1052S-1057S
Fuller R. A review: probiotics in man and animals. J Appl Bacteriol 1989; 66:365-738
14. 14 PROBIÓTICOS: REQUISITOS (I) De origen humano
No ser patógena
No ser sensible a enzimas proteolíticas
Ser capaz de vivir en tránsito gástrico
No conjugarse con sales biliares
Capacidad de adhesión y colonización
Adherencia a células epiteliales
15. 15 PROBIÓTICOS: REQUISITOS (II) Sobre vivencia en el ecosistema intestinal
Producción de componentes antimicrobianos
Permanencia prolongada y estable
Inmunoestimulación
16. 16 INMUNOMODULACIÓN Se basa en tres principios:
Reconocimiento del antígeno
Destrucción del mismo
Regulación del material destruido
17. 17 FUNCIÓN INMUNOLÓGICA Aumenta actividad fagocítica
Aumenta producción de linfocitos
Aumenta actividad de células NK
Reduce producción de citoquinas
Aumenta producción de Interleuquinas
Inhibición de agentes carcinogénicos
Incremento de IgA total y específica
18. 18 FACTORES QUE DISMINUYEN LA POBLACIÓN DE PROBIÓTICOS Estrés
Envejecimiento
Antibioticoterapia
Quimioterapia y radioterapia
Anticonceptivos
Alcohol
Diarrea intermitente
Desnutrición
19. 19 PREBIÓTICOS The definition of a prebiotic has recently been redefined by Gibson and Probert as a selectively fermented ingredient that allows specific changes, both in the composition and/or activity in the gastrointestinal microflora, that confers benefits upon host well-being and health.
This definition is broader than the previous one by Gibson and Roberfroid (1995) which referred only to the specific effects of prebiotics on colonic bacteria.
In other words, a prebiotic is a food ingredient which is undigested and serves as a growth substrate for beneficial bacteria in the GI tract, thereby providing one or more health benefits.
References:
Gibson GR et al. J Nutr, submitted 2003
Gibson GR, Roberfroid MB. J Nutr 1995; 125:1401-1412
The definition of a prebiotic has recently been redefined by Gibson and Probert as a selectively fermented ingredient that allows specific changes, both in the composition and/or activity in the gastrointestinal microflora, that confers benefits upon host well-being and health.
This definition is broader than the previous one by Gibson and Roberfroid (1995) which referred only to the specific effects of prebiotics on colonic bacteria.
In other words, a prebiotic is a food ingredient which is undigested and serves as a growth substrate for beneficial bacteria in the GI tract, thereby providing one or more health benefits.
References:
Gibson GR et al. J Nutr, submitted 2003
Gibson GR, Roberfroid MB. J Nutr 1995; 125:1401-1412
20. 20 SIMBIÓTICOS(ALIMENTOS FUNCIONALES)
PROBIÓTICOS
+
PREBIÓTICOS
21. 21
PROBIÓTICOS
(1.965)
PREBIÓTICOS
(1.995)
SIMBIÓTICOS
(2.001)
22. 22 The first component comprises galacto-oligosaccharides.
These are carbohydrates which are built up from galactose and glucose.
This fraction consists of a mixture of linear molecules with a chain length of two to six sugar molecules.
The first component comprises galacto-oligosaccharides.
These are carbohydrates which are built up from galactose and glucose.
This fraction consists of a mixture of linear molecules with a chain length of two to six sugar molecules.
23. 23 Galacto-oligosaccharides are consumed by infants in several naturally occurring forms.
They are components of human milk and are also by products of lactose hydrolysis in fermented milk and milk products.
Therefore, they are a natural part of the human infant diet.
Galacto-oligosaccharides are consumed by infants in several naturally occurring forms.
They are components of human milk and are also by products of lactose hydrolysis in fermented milk and milk products.
Therefore, they are a natural part of the human infant diet.
24. 24 Fructo-oligosaccharides are natural storage carbohydrates present in many plants such as chicory, banana, wheat and leeks.
These oligosaccharides are therefore natural food components.Fructo-oligosaccharides are natural storage carbohydrates present in many plants such as chicory, banana, wheat and leeks.
These oligosaccharides are therefore natural food components.
25. 25 TRÓFICAS
Control de la proliferación y diferenciación de células epiteliales; desarrollo y homeostasis del sistema inmunitario.
PROTECTORAS
Protección contra patógenos (el Efecto Barrera).
METABÓLICAS
Fermentación de los residuos alimentarios no digeridos y moco endógeno: recuperación de energía en forma de ácidos grasos de cadena corta, producción de vitamina K, absorción de iones. PRINCIPALES FUNCIONES DE LA MICROBIOTA INTESTINAL
26. 26 AGENTES BIOTERAPÉUTICOS
27. 27 AGENTES BIOTERAPÉUTICOS
28. 28
29. 29 AGENTES BIOTERAPÉUTICOS
30. 30 AGENTES BIOTERAPÉUTICOS
31. 31 EFICACIA DE LOS PROBIÓTICOS RECOMENDACIÓN DE GRADO A (Datos de nivel 1A)
Tratamiento de la diarrea infecciosa aguda en niños
Prevención de la diarrea asociada a los antibióticos
Prevención de la diarrea nosocomial y adquirida en niños
Diarrea en niños
Tratamiento de la mal absorción de lactosa
32. 32 BACILLUS CLAUSII PRINCIPIO ACTIVO:
Microorganismo gram positivo, aerobio estricto, con tolerancia alcalina (capacidad de crecer a un ph = 7 y superior), no patógeno y ubicuo, encontrándose incluso en el intestino humano.
Puede existir en forma de esporas resistente a condiciones físicas y química adversas.
80% de sujeto sanos (heces) 104107 x gr. de heces
33. 33 ESPORAS DE
BACILLUS CLAUSII
34. 34 PROPIEDADES DEL BACILLUS CLAUSII Capaz de colonizar y sobrevivir en el tracto gastrointestinal.
Produce inhibición en la adherencia de bacterias patógenas.
Produce sustancias antimicrobianas.
Resistente a diversos antibióticos y al mismo tiempo
no trasmite esta resistencia a gérmenes patógenos.
Tiene efecto inmunomodulador.
35. 35 ESPORAS BACTERIANAS (BACILLUS CLAUSII)
PROPIEDADES
Resistencia al ácido: Sobrevive a la exposición de jugos gástricos naturales y artificiales.
Resistencias a sales biliares.
Resistencia al calor.
36. 36 Entre 20°c- 45 °c en medio líquido
50°c en medio sólido
Óptimo 35 °c- 40 °c
No crecen = 55 °c
37. 37 BACILLUS CLAUSII CARACTERÍSTICAS GENERALES Cuatro cepas:
O/C
N/R
T
SIN
38. 38 INDICACIONES Diarrea infecciosa
Diarrea del viajero
Diarrea secundaria a antibióticos
Trastorno inflamatorio intestinal
Colon irritable
Deficiencia de lactasa
Reducción de colesterol
Enfermedad Alérgica
Infección por H. Pylori
Pancreatitis ?
39. 39 Infección por H. Pylori
40. 40 Evidencia basada en metaánalisiscon B. Clausii
41. 41 Evidencia basada en metaánalisiscon B. Clausii
42. 42 BACILLUS CLAUSII
CONTRAINDICACIÓN:
HIPERSENSIBILIDAD CONOCIDA A SU COMPOSICIÓN.
PRECAUCIÓN:
DURANTE LA ANTIBIOTICOTERAPIA, ADMINISTRARLO EN EL INTERVALO DE DOS DOSIS.
43. 43 BACILLUS CLAUSII
INTERACCIÓN:
NO SE CONOCEN.
EMBARAZO Y LACTANCIA:
NO ESTÁ CONTRAINDICADO.
CAPACIDAD DE CONDUCCIÓN:
NO INTERFIERE.
44. 44 BACILLUS CLAUSII
EFECTOS INDESEADOS:
NO SE HAN REPORTADO.
SOBREDOSIS:
NO SE HAN DESCRITO.
45. 45
46. 46 CONCLUSIONES Por sus características biológicas Bacillus Clausii es una alternativa eficaz y segura en el tratamiento o prevención de la diarrea por antibióticos
Las evidencias hasta ahora sugieren que Bacillus Clausii probablemente tenga una influencia positiva en todas aquellas entidades relacionadas con desequilibrio en la microflora intestinal:
* sobrecrecimiento bacteriano (intestino irritable, síndrome intestino corto, trastornos en la motilidad
intestinal)
47. 47 RECOMENDACIÓN DE ESPGHAN
ESPGHAN:European Society of Pediatric Gastroenterology, Hepatology and Nutrition Committee on Nutrition.
Agostoni C, Axelsson I, Bregger C, et al.
Probiotic bacteria in dietetic products for infants: a commentary by the ESPGHAN Committee on Nutrition.
J. Pediatr Gastroenterol Nutr 2004;38(4):365-74
48. 48