MICROBIOTA/MICROBIOMA INTESTINAL

PEDIATRIA Hospital Alberto Sabogal Sologuren

 El TGI, va desde labios hasta ano Area ms grande contacto con el medio externo.

Definicin
Ecosistema abierto que comprende una amplia variedad de poblaciones microbianas metablicamente activas que coexisten en una regin espacio temporal definida y que juegan un importante papel en la salud del husped.

ALIM. NUTRI. SALUD Vol. 11, N. 2, pp. 37-48, 2004

> 95% de bacterias de la microbiota intestinal viven en el colon.

ALIM. NUTRI. SALUD Vol. 11, N. 2, pp. 37-48, 2004

Desarrollo de la Flora Intestinal Normal

Intrautero
el intestino : medio esteril

Al nacer
El RN adquiere bacterias del canal del parto y LM Bifidobacterias y lactobacilos

Nacidos por CESAREA

Se colonizan del ambiente hospitalario

Nacidos por VIA VAGINAL

1 dia de vida: heces : Escherichia coli y Enterococcus 5 dia de vida: Bifidobacterium spp
An Pediatr, Monogr. 2006;4(1):12-9

 Los que reciben LM

Predominan Bifidobaterias y bacterias productoras de acido lactico, pocos bacteroides, clostridios y otras

Los que reciben FM

Predominio de bacteroides, clostridium

el tamao de estas poblaciones es muy variable.

An Pediatr, Monogr. 2006;4(1):12-9

 RNPT, flora intestinal muy pobre

Numero bajo de especies bacterianas Primeros 10 dias: E. coli y Klebsiella spp., enterococos como E. faecalis y estafilococos como Staphylococcus epidermidis, S. aureus y S. haemolyticus, Bifidobacterias, instalacion mas tardia

An Pediatr, Monogr. 2006;4(1):12-9

LM y microbiota
Factores de la LM N-acetilglucosamina, Glucosa, Lactoferrina, La galactosa, la fructosa Favorecer el crecimiento de bifidobacterias

 Introduccion de alimentacionc omplementaria

Flora intestinal del adulto Predominan bacteroides y otras bacterias gramnegativas

A los dos aos de vida, se establece hasta la adultez

ALIM. NUTRI. SALUD Vol. 11, N. 2, pp. 37-48, 2004

Funciones de la Microbiota Intestinal

Funcion metabolica
Sintesis de vitaminas: K Produccion enzimatica: lactasa Trasnformacion de sales biliares Digestion y absorcion de nutrientes

 Funcion trofica
Nutricion del epitelio intestinal: 50% de energia aprox es suministrada por la flora intestinal y estimulan el desarrollo de las vellosidades intestinales.

Funcion protectora
Barrera intestinal Barrera mecanica Barrera inmunologica

Interaccion entre el husped y la Microbiota intestinal

(a) During gut homeostasis, while maintaining a polarized configuration (with intact tight junctions), enterocytes are tolerant to TLR stimulation by normal microflora, and NF-B activation is low. Secretion of -defensin by Paneth cells helps control the amount of intestinal microflora. PGN, peptidoglycan; CpG, CpG oligo deoxynucleotides; DC, dendritic cell. (b) Activation of IKK and NF-B in response to trichuris infection results in TSLP secretion, which 'instructs' dendritic cells to induce a TH2 response with eosinophils and immunoglobulin E (IgE)secreting B cells, thus eradicating the parasite. The -defensins and -defensins secreted by Paneth cells and enterocytes, respectively, control the microflora. p50 and p65, NF-B subunits. (c) Deficiency in IKK or NEMO (possibly representing ectodermal dysplasia with immune deficiency) leads to a lack of TSLP and -defensin production, causing dendritic cells to secrete IL-12 and IL-23, which induces a TH1 and IL-17-secreting T helper (TH-17) response and, consequently, a chronic inflammatory reaction. Tissue damage ensues, due to the accumulation of neutrophils and other inflammatory cells and the secretion of proapoptotic cytokines such as TNF. M, macrophage; G-CSF, granulocyte colony-stimulating factor. (d) In Paneth cells, gain-of-function mutations in the gene encoding Nod2 (mNod2) with hypersensitivity to muramyl dipeptide (MDP) result in excessive NF-B activation, with secretion of a hypothetical cytokine that forces DCs to release IL-12 and IL-23. The outcome is induction of a TH1 and an IL-17-secreting T helper response that promotes tissue damage and Crohn's colitis. Alternatively, loss-of-function mutations in the gene encoding Nod2 compromise NF-B activation and the production of a TSLP-like factor, also resulting in TH1-driven colitis. IFN g-, interferon g-.

MICROFLORA Y PROBIOTICOS

(a) During gut homeostasis, while maintaining a polarized configuration (with intact tight junctions), enterocytes are tolerant to TLR stimulation by normal microflora, and NF-B activation is low. Secretion of -defensin by Paneth cells helps control the amount of intestinal microflora. PGN, peptidoglycan; CpG, CpG oligo deoxynucleotides; DC, dendritic cell. (b) Activation of IKK and NF-B in response to trichuris infection results in TSLP secretion, which 'instructs' dendritic cells to induce a TH2 response with eosinophils and immunoglobulin E (IgE)secreting B cells, thus eradicating the parasite. The -defensins and -defensins secreted by Paneth cells and enterocytes, respectively, control the microflora. p50 and p65, NF-B subunits. (c) Deficiency in IKK or NEMO (possibly representing ectodermal dysplasia with immune deficiency) leads to a lack of TSLP and -defensin production, causing dendritic cells to secrete IL-12 and IL-23, which induces a TH1 and IL-17-secreting T helper (TH-17) response and, consequently, a chronic inflammatory reaction. Tissue damage ensues, due to the accumulation of neutrophils and other inflammatory cells and the secretion of proapoptotic cytokines such as TNF. M, macrophage; G-CSF, granulocyte colony-stimulating factor. (d) In Paneth cells, gain-of-function mutations in the gene encoding Nod2 (mNod2) with hypersensitivity to muramyl dipeptide (MDP) result in excessive NF-B activation, with secretion of a hypothetical cytokine that forces DCs to release IL-12 and IL-23. The outcome is induction of a TH1 and an IL-17-secreting T helper response that promotes tissue damage and Crohn's colitis. Alternatively, loss-of-function mutations in the gene encoding Nod2 compromise NF-B activation and the production of a TSLP-like factor, also resulting in TH1-driven colitis. IFN g-, interferon g-.

 In the initial stage of immune response, the innate immune system recognizes the presence of pathogens and provides the first line of defense. Dendritic cells which are circulating through the tissue has the ability to recognize presence of pathogen associated molecular patterns or PAMPs. PAPMs are conserved features of pathogens such as lipopolysaccharides (LPS) that are components of the cell membrane of all gram-negative bacteria. Dendritic cells have the ability to recognize PAMPs through the expression of family of Toll like receptors (TLRs). In the case of LPS it is recognize by TLR4 receptor, which is expressed in the surface of dendritic cells. LPS is transported by a soluble LPS binding protein (LBP) to the surface of dendritic cells, And its deposited in cell surface protein (CD14). The presence of LPS is detected by TLR4 though its interaction and recognition of the LPS bound CD14. The signal delivered by TLR initiates maturation of dendritic cell. Dendritic cell can now migrate to regional lymph nodes and activate required immune response

TRANSLOCACION BACTERIANA
Paso de bacterias viables por el epitelio TGI Endotoxinas y bacterias muertas en pequeas cantidades cumple un rol fisiologico. estimulo fisiologico RES (kupffer). T. bacteriana: predominio de Aerobios gram Escherichia. Proteus. Klebsiella Via linfatica g mesentericos, higado bazo Generaliza : sepsis, shock, FO multisistemica.

En modelos animales: Shock hemorragico Quemaduras Trauma Isquemia Obstruccion intestinal Falla aguda hepatica, cirrosis Pancreatitis severa

3 mecanismos:
Sobrecrecimiento intestino delgado. Incremento de la permeabilidad de la barrera mucosa. Alteracion de defensas inmuntarias

 Translocacion B. esta asoacida con desarrollo de Sepsis post operatoria. Cirrosis (sobrecrecimiento bact. Intest. Delgado), peritonitis espontanea y complicaciones hepaticas.

ORIGEN DE LOS PROBITICOS

Elie Metchnikoff (1.845 1.916) Ciertas clulas son capaces de engullir cuerpos extraos. Probitico: a favor de la vida
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PROBITICOS
Probiticos son microbios vivos en la comida suplementaria (incluyendo leche fermentada y productos OTC) que afectan benficamente el huesped al mejorar su balance intestinal microbiano.
Collins MD, Gibson GR, 1999
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PROBITICOS: REQUISITOS (I)

De origen humano No ser patgena No ser sensible a enzimas proteolticas Ser capaz de vivir en trnsito gstrico

No conjugarse con sales biliares

Capacidad de adhesin y colonizacin Adherencia a clulas epiteliales
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PROBITICOS: REQUISITOS (II)

Sobre vivencia en el ecosistema intestinal
Produccin de componentes antimicrobianos Permanencia prolongada y estable Inmunoestimulacin

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INMUNOMODULACIN
Se basa en tres principios: Reconocimiento del antgeno Destruccin del mismo

Regulacin del material destruido

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FUNCIN INMUNOLGICA
Aumenta actividad fagoctica
Aumenta produccin de linfocitos Aumenta actividad de clulas NK

Reduce produccin de citoquinas

Aumenta produccin de Interleuquinas Inhibicin de agentes carcinognicos Incremento de IgA total y especfica

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FACTORES QUE DISMINUYEN LA POBLACIN DE PROBITICOS

Estrs Envejecimiento Antibioticoterapia Quimioterapia y radioterapia Anticonceptivos Alcohol Diarrea intermitente Desnutricin
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PREBITICOS
UN prebitico es un ingrediente selectvamente fermentado que permite cambios especficos, tanto en la composicin y/o actividad en la microflora gastrointestinal, que confiere beneficios en la salud del huesped.
Gibson GR, Probert HM et al., submitted (2003)

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(ALIMENTOS FUNCIONALES)

SIMBITICOS

PROBITICOS

+
PREBITICOS
88

PROBITICOS
(1.965)

PREBITICOS
(1.995)

SIMBITICOS
(2.001)
89