Dr. Tinahones Madueño - fesemi.org · Ln ch Ob ch Dieta: LF-HPP ... 392–397, 2011. PRODUCCION DE...
Transcript of Dr. Tinahones Madueño - fesemi.org · Ln ch Ob ch Dieta: LF-HPP ... 392–397, 2011. PRODUCCION DE...
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Francisco J. TinahonesServicio de Endocrinología y Nutrición.
Hospitales Regional y Virgen de la Victoria de Málaga
MICROBIOTA INTESTINAL
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GUION
• EPIDEMIOLOGIA
• MICROBIOTA OBESIDAD Y DIABETES
• MECANISMOS
• ¿COMO SE MODIFICA LA MICROBIOTA?
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Qué es la microbiota?
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MICROBIOTA
• Tienen un peso de
1.5 Kg
• Superan al genoma
humano en 100-
veces
• Tres trillones de
gérmenes
• 1000 especies
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MICROBIOTA-
EDAD
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FUNCIONES DE LA MICROBIOTA
FUNCIÓN INMUNE� Destrucción toxinas /carcinógenos
� Colonización por bacterias patógenas� Desarrollo del SI
� Modulación del estado inflamatorioFUNCIÓN DIGESTIVA� Motilidad digestiva
� Síntesis micronutrientes� Absorción electrolitos/ minerales
� Fermentación sustancias indigeribles
Gill, SR et al. Metagenomic analysis of the human distal gut microbiome. Science. 2006; 312 (5778): 1355-59.
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0
5
10
15
20
25
30
35
40
45
50
1950 1960 1970 1980 1990 2000 2010
BMI
PHYSICAL ACTIVITY
INTAKE
BMI-ESTILOS DE VIDA
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¿ Se han producido cambios de la microbiota en las últimas
décadas?
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PERDIDA DE BIODIVERSIDAD EN EL INTESTINO
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CAMBIOS EN ECOLOGIA HUMANA AFECTAN A LA COMPOSICIÓN DE
LA MICROBIOTACHANGE CONSEQUENCES
Water sanitation Fecal transmission decrease
Cesarean surgery increase Vaginal transmission decrease
Increase of the antibiotic use in preterm Vaginal transmission decrease
Lactation reduction Cutaneous transmission decrease
Small families Early contamination decrease
Antibiotic use increase Microbiota changes
Antibacterial soaps and toiletries increase Microbiota changes
Mercury-amalgam dental filling increase Microbiota changes
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B. FASO CHILDREN EUROPEAN CHILDREN
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METODOS DE DETERMINACION DE LA MICROBIOTA
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MICROBIOTA OBESIDAD
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Turnbaugh, PJ et al. Nature. 2006; 444 (7122): 1027-31.
ob/ob ob/+ +/+ Libres de gérmenes
+/+
ob/ob
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COMPOSICIÓN DE LA FLORA EN OBESOS/DELGADOS
�Enobesos < Bacteroidetes> Firmicutes
Ley R et al.Nature. 2006; 444 (7122): 1022-23.
► Tras pérdida de peso aumento de proporción de bacteroidetes
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Million M et al. Int J Obes 2011 Aug
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obesodelgado
ObLn
Dieta LF-HPP: baja en grasa-alta en polisacáridos de vegetales.
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Ln ch
Ob ch
Dieta: LF-HPP
Ob ch : Menor aumento de la adiposidad que el Ob (similar a Ln o Ln ch)
Dieta HiSF-LoFV: alta en grasas saturadas, baja en frutas y verduras
Dieta LF-HPP: baja en grasa-alta en polisacáridos vegetales.
Conclusión: Las interacciones modificables y transmisibles entre la dieta y la microbiota influyen en la biología del hospedador.
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DIABETES MICROBIOTA
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Junjie Qin et al. Nature 2012;490:55–60
Microbiota intestinal en diabetes tipo 2. Cohorte China
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Junjie Qin et al. Nature 2012;490:55–60
Microbiota intestinal en diabetes tipo 2. Cohorte China
• Los pacientes con T2D tenían un descenso en especies
productoras de butirato. Roseburia intestinals y F
prausnitzii.
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Microbiotaintestinal en
diabetes tipo 2.
Cohorte EU
Nature. 2013 Jun 6;498(7452):99-103
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Hallazgos mayores en el análisisdel metagenoma en diabetes tipo
2• Descenso de bacterias productoras de butirato
como Roseburia intestinalis and Faecalibacterium prausnitzii
• Lactobacillus gasseri and Streptococcus mutans y ciertos Clostridiales mas elevados en T2D
• Proteobacteria más alta en T2D
• Incremento de expresión de genes de la microbiotaenvueltos en estrés oxidativo e inflamación
Tilg H et al. Gut. 2014 Sep;63(9):1513-21
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OBESOS MORBIDOS SIN IR
Parameters Control No-IR morbid obese subjects
IR morbid obese
subjects
N (men/women) 8 (5/3) 13 (8/5) 13 (8/6)
Age (years) 54.0 ± 17.8 45.2+10.9 38.8+8.6
Weight (kg) 71.3 ± 7.3 b 156.3+32.4a 155.2+25.5a
BMI (Kg/m 2) 28.6 ± 4.1 b 56.4+7.4a 55.8+6.1a
Waist (cm) 83.4±7.5 b 145.8+24.3a 142.5+17.6a
HOMA-IR 2.57+2.23 b 2.73+0.99 b 12.92+4.57a
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M M♀♂ ♀♂
Insulin Sensitive Insulin Resistant
Serino M et al. Act Diabetol 2012
TAXONOMIC DIFFERENCES BETWEEN APPENDICES FROM MORBIDLY OBESE INSULIN SENSITIVE AND RESISTANT
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Serino M et al. Act Diabetol 2012
• MICROBIOTA
DIFFERENCES
BETWEEN THE
APPENDIX
FROM
MORBIDLY
OBESE
SUBJECTS
WITH OR
WITHOUT
INSULIN
RESISTANCE
IR
NO IR
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0
20
40
60
80
100
IR NoIR
Re
lati
ve A
bu
nd
an
ce (
%)
Phyla
Proteobacteria
Fusobacteria
Firmicutes
Bacteroidetes
Taxon IR NoIR P
Bacteroidetes 58,87 48,22 7,8E-03
Firmicutes 24,88 22,34 3,84E-09
Fusobacteria 10,34 0,78 4,90E-04
Proteobacteria 5,89 28,64 1,1E-03
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MECANISMOS :RELACION MICROBIOTA OBESIDAD
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Fermentación sustancias indigeribles
Firmicutes intestinales
Polisacáridos
indigeribles
SCFAH2
(-)
Energía
Metano
M Smithii (Archaea)
Raoult, D. Obesity pandemics and the modification of digestive bacterial flora. Eur J Clin Microbiol Infect Dis. 2008; 27: 631-634.
Monosacáridos
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REGULACION BALANCE ENERGETICO
20 KILOCALORIAS
MAS AL DIA 20 AÑOS
20 KILOSMAS
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Modificación de la secreción de incretinas
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REGULACION BALANCE ENERGETICO
Propiomelanocortina (POMC)
Transcriptasa cocaína-amfetamina
Colecistoquinina
Péptido YY
Leptina
Neuropéptido Y
Proteína r-Agouti
Grelina
-
-
--
+
GLP
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MECANISMOS :RELACION MICROBIOTA DIABETES
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Microbiota/Diabetes causalidad
ENDOTOXEMIA
PRODUCCION DE BUTIRATO
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ENDOTOXEMIA
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NIVELES BASALES DE LPS E INCIDENCIA DE DIABETES
Diabetes Care 34:392–397, 2011
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PRODUCCION DE BUTIRATO
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Washout
Crossover, randomized, controlled
10 volunteers with cardiovascular risk factors
1st Intervention20 days
272 ml RED WINE
1st Intervention20 days
272 ml DEALCOHOLIZEDRED WINE
(Polyphenol Control)
1st Intervention20 days
100 ml GIN(Alcohol Control)
2nd Intervention20 days
272 ml RED WINE
2nd Intervention20 days
272 ml DEALCOHOLIZEDRED WINE
(Polyphenol Control)
2nd Intervention20 days
100 ml GIN(Alcohol Control)
3rd Intervention20 days
272 ml RED WINE
3rd Intervention20 days
272 ml DEALCOHOLIZEDRED WINE
(Polyphenol Control)
3rd Intervention20 days
100 ml GIN(Alcohol Control)
FECES
STUDY DESIGN
WINE MICROBIOTA
FECES FECES FECES
Dr F. J. TinahonesServicio de Endocrinología
Nutrición. Hospital Universitario Virgen de la Victoria de Málaga. CIBEROBN (CB06/03/010), Instituto de Salud Carlos III, Málaga, Spain .
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EFFECTS OF MODERATE WINE CONSUMPTION IN SUBJECTS WITH
CARDIOVASCULAR RISK ON THE MICROBIAL COMPOSITION IN FECES
Bacteroides spp
Firmicutes (phylum)
Enterococcus spp
Clostridium spp
Prevotella spp
Fusobacteria (phylum)
Lactobacillus spp
Bifidobacterium spp
Bacteroidetes (phylum)
RESULTS
Queipo-Ortuño MI. Am J Clin Nutr 2012
Boto M et al Food Funct. 2014 Aug;5(8):1932-8.
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Vino y LPS
Clemente M et al. Am J Clin Nutr 2013
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DIETA vs HORMONAS SEXUALES
• DIETA BAJA EN GRASA Y ALTA
• CRIAS SIN OVARIOS VS CRIAS DE MADRES
ANDROGENIZADAS
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HFD LFD
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ooforectomíacontrolA OVXC
A: Firmicutes
Bacterioidetes
A: Prevotellaceae
Bacterioidaceae
A: Lachnospiraceae
Vellonaceae
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GASTROENTEROLOGY 2012;143:913–916
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GASTROENTEROLOGY 2012;143:913–916
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Cristina AndrésLacueva
Institut d'Investigació Biomèdica de GironaJosé Manuel Fernández-Real
Nutrition & Food Science Department.
Nutritional and Food Metabolomic GroupUniversidad de CórdobaManuel Tena Francisco Perez Jimenez
Institut National de la Santé et de la Recherche Médicale, Toulouse, FranceRemi Burcelin