Microbiota intestinal: Su relación con la inflamación....Microbiota intestinal es considerada un...

Microbiota intestinal:

Su relación con la inflamación.

Dr. Alberto Penas Steinhardt pufetin@gmail.com

Laboratorio de Genómica Computacional-UNLu.

División Endocrinología Hospital de Clínicas “José de San Martín”

IDEHU, CONICET-UBA Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires

Relación entre el Sistema Inmune y el mundo

microbiano

Dr. Alberto Penas Steinhardt IDEHU, CONICET-UBA

División Endocrinología - Hospital de Clínicas “José de San Martín”

pufetin@gmail.com

Louis Pasteur Robert Koch

Teoría germinal de las enfermedades

infecciosas

Postulados de Koch

pufetin@gmail.com

The relationship between the metazoan

immune system and the microbial world.

Muraille E (2013) Redefining the Immune System as a Social Interface for Cooperative Processes. PLoS Pathog 9(3):

Interacción Negativa

Interacción Positiva

Transferencia Horizontal de genes

pufetin@gmail.com

Simbiosis Cooperativa

Interacción Negativa

Interacción Positiva

Transferencia Horizontal de genes

pufetin@gmail.com

Las infecciones favorecen la circulación de

innovaciones genéticas

pufetin@gmail.com

El sistema inmune innato ha

evolucionado en respuesta a la

necesidad de controlar los microbios

beneficiosos residentes antes que para

defenderse contra patógenos

invasores.

Rethinking the role of immunity: lessons from Hydra.

Bosch TC1. Trends Immunol. 2014 Oct;35(10):495-502.

Microbiota intestinal .

pufetin@gmail.com

Microbiota intestinal es considerada un órgano integrado en la

fisiología del individuo.

“supra-organismo”, compuesto por células

humanas y células microbianas.

•supera ~ 10 veces el número total de nuestras

propias células humanas

•Los genomas totales de estas especies Intestinales

(microbioma) Contiene 100 veces más Genes que

nuestro genoma "propio"

•El microbioma es una parte integral De nuestro

paisaje genético (Metagenoma humano) y de Nuestra

evolución genética

pufetin@gmail.com

División Endocrinología

Hospital de Clínicas “José de San Martín”

20.000-25.000

protein-coding genes

4-5 million non-redundant

bacteria genes

División Endocrinología

Hospital de Clínicas “José de San Martín”

pufetin@gmail.com

Human microbiota: onset and shaping

through life stages and perturbations

The function of our microbiota: who is out there and what do they do? Front. Cell. Infect. Microbiol. 09 August 2012

pufetin@gmail.com

Wajiha Gohir et al

Pediatric Research (2015) 77, 196–204

pufetin@gmail.com

Wajiha Gohir et al

Pediatric Research (2015) 77, 196–204

pufetin@gmail.com

Bacterial 16S rRNA gene surveys reveal that the first

microbiotas of human newborns are primarily

structured by delivery mode.

Maria G. Dominguez-Bello et al. PNAS 2010;107:11971-11975

pufetin@gmail.com

Human milk contains an

unexpected abundance and

diversity of

complex oligosaccharides

apparently indigestible by the

developing

infant and instead targeted to

its cognate gastrointestinal

microbiota.

pufetin@gmail.com

Current Opinion in Biotechnology, Volume 44, 2017, 63–68

Physiological and behavioral pathways linking infant feeding, growth, and the development of pediatric obesity. AMERICAN

JOURNAL OF HUMAN BIOLOGY 24:350–360 (2012)

Developmental Origins of Obesity: Early Feeding Environments,

Infant Growth, and the Intestinal Microbiome

pufetin@gmail.com

OBJECTIVE To assess the impact of antibiotics

prescribed in infancy (ages 0-23 months) on

obesity in early childhood (ages 24-59 months).

DESIGN, SETTING, AND PARTICIPANTS We

conducted a cohort study spanning 2001-2013

using electronic health records. … The cohort

comprised 64 580 children.

Association of antibiotics in infancy with early childhood

obesity.

Bailey LC, et al. JAMA Pediatr. 2014 Nov;168(11):1063-9.

pufetin@gmail.com

Gut microbiota composition in African children living in rural areas with a polysaccharide-rich

diet when compared with Italian city children.

Simrén M et al. Gut doi:10.1136/gutjnl-2012-302167

pufetin@gmail.com

Alteración de la Microbiota Intestinal y

Procesos Inflamatorios Crónicos

pufetin@gmail.com

Endotoxemia metabólica e insulino resistencia

pufetin@gmail.com

Clinical & Translational Immunology (2017) 6, e125; doi:10.1038/cti.2016.91

Published online 20 January 2017

Alteración de la

Microbiota Intestinal y

Procesos Inflamatorios

Crónicos

pufetin@gmail.com

Protección contra

Patógenos invasores

Exclusión competitiva

Promueve producción de IgA

pufetin@gmail.com

Science 341, 1069 (2013);

pufetin@gmail.com

Microbiology. Fighting obesity with bacteria.

Walker AW et al. Science. 2013 Sep 6;341(6150):1069-70

los genes microbianos son una mejor lectura predictiva respecto a

la predisposición de desarrollar obesidad o sobrepeso

precisión 58%

precisión 90%

pufetin@gmail.com

Alteraciones en la Microbiota y Diabetes Tipo 2

Science 341, 1069 (2013);

pufetin@gmail.com

Gut metagenome in European women with normal, impaired

and diabetic glucose control

F.H. Karlsson et al. Nature 498, 99–103 (06 June 2013)

Science 341, 1069 (2013);

pufetin@gmail.com

b,Aschematic diagram showing the main functions of the gut microbes that had a predicted T2D association. Red text denotes

enriched functions in T2D patients; blue text denotes depleted functions in T2D patients (345 Chinese individuals)

A metagenome-wide association study of gut microbiota in type

2 diabetes

Qin J. et al. Nature. 2012 Oct 4;490(7418):55-60.

pufetin@gmail.com

Cada población es un mundo

pufetin@gmail.com

Science 341, 1069 (2013);

pufetin@gmail.com

Microbiota intestinal en población de Buenos Aires.

Science 341, 1069 (2013);

pufetin@gmail.com

Buenos Aires Rosario

Penas-Steinhardt Vazquez

Science 341, 1069 (2013);

pufetin@gmail.com

Microbiota, communicate among themselves and

exchange signals with the animal’s organ systems,

participating in the body’s homeostasis.

The ancestry of humans reflected in the genomic

signature. A phylogenetic analysis of the human

genes reveals the relative percentage of the

genome that arose at a series of stages in

biological evolution.

Patologías asociadas a cambios en la microbiota

intestinal

pufetin@gmail.com

• Diabetes tipo 2 / Obesidad

• Enfermedades autoinmunes

• Lupus

• Enfermedad celíaca

• Autismo

• Alergias

• Inflamatorias intestinales (CU y Crohn)

Gracias !

pufetin@gmail.com

Fig. 3. Direct administration of Bifidobacterium to TAC recipients with

established tumors improves tumor-specific immunity and response to

αPD-L1 mAb therapy.

Science. 2015 Nov 27;350(6264):1084-9

Terapéuticas potenciales

•Prebióticos - hidratos de

carbono no digestibles

(fructooligosacáridos)

•Probióticos - Bifidobacterium,

Lactobacillus,

Saccharomyces boulardii

•Antibióticos

•trasplante fecal

•Modificación de hábitos

alimentarios

pufetin@gmail.com

Microbiota intestinal

pufetin@gmail.com

Disturbance in Gut Microbiota;

DIET & NUTRITION

pufetin@gmail.com

1979: Hassle-Free Daily Food Guide

Based on the Basic Four, but also

included a fifth group to highlight the

need to moderate intake of fats, sweets,

and alcohol

pufetin@gmail.com

Gut microbiota and carbohydrates

Cellulose is one of the substrates for

the short-chain fatty acid (SCFA)

production

pufetin@gmail.com

Journal of Psychiatric Research (2015)

Science 341, 1069 (2013);

pufetin@gmail.com

We identify Non-caloric artificial sweeteners (NAS)-altered microbial metabolic pathways that

are linked to host susceptibility to metabolic disease, and demonstrate similar NAS-induced

dysbiosis and glucose intolerance in healthy human subjects. Collectively, our results link

NAS consumption, dysbiosis and metabolic abnormalities, thereby calling for a

reassessment of massive NAS usage.

Artificial sweeteners induce glucose intolerance by altering the

gut microbiota

Jotham S et al. Nature 514, 181–186 (09 October 2014)

Science 341, 1069 (2013);

pufetin@gmail.com

Dietary emulsifiers impact the mouse gut microbiota promoting

colitis and metabolic syndrome

Benoit C et al. Nature 519, 92–96 (05 March 2015)

Emulsifier-induced metabolic syndrome was associated with microbiota encroachment,

altered species composition and increased pro-inflammatory potential. Use of germ-free mice

and faecal transplants indicated that such changes in microbiota were necessary and

sufficient for both low-grade inflammation and metabolic syndrome.

These results support the emerging concept that perturbed host–microbiota interactions

resulting in low-grade inflammation can promote adiposity and its associated metabolic

effects. Moreover, they suggest that the broad use of emulsifying agents might be

contributing to an increased societal incidence of obesity/metabolic syndrome and

other chronic inflammatory diseases.

pufetin@gmail.com

Science 341, 1069 (2013);

pufetin@gmail.com

Drugging the gut microbiome

Ken Garber. Nature Biotechnology 33, 228–231 (2015)

Science 341, 1069 (2013);

pufetin@gmail.com

Drugging the gut microbiome

Ken Garber. Nature Biotechnology 33, 228–231 (2015)

pufetin@gmail.com

The relationship between the metazoan

immune system and the microbial world.

Muraille E (2013) Redefining the Immune System as a Social Interface for Cooperative Processes. PLoS Pathog 9(3):

pufetin@gmail.com

Las infecciones favorecen la circulación de

innovaciones genéticas

pufetin@gmail.com

Factores de transcripción

PPAR-γ

Receptores

TLR1-9, TNF-R, IL6-R, Leptina

Citoquinas

TNF, IL-1, IL-2, IL-6, IL-10

Quimiocinas

CCL2, CCL5, CCL3

Complemento

C3, C1q

Adipoquinas

Adiponectina, Leptina

Macrófago

Adipocito

El tejido adiposo, un órgano endócrino e inmunológico

pufetin@gmail.com

Dieta Paleolítica

Frutas, vegetales,

Carne cruda,

frutos secos,

pescado,

huevos

Dieta Occidental

carne y aves 12,8%

Azucar y

Pescado 0,6%

Edulcorantes

Lacteos 8,6

Huevos 1,4%

Grasas y

Aceites

Legumbres y

frutos secos

pufetin@gmail.com

Microbiota intestinal: Su relación con la inflamación....Microbiota intestinal es considerada un...

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