Exploring the link between gut microbiota and metabolic health Ellen Blaak Professor in Physiology of fat metabolism, Department of Human Biology NUTRIM School of Nutrition and Translational Research in Metabolism Maastricht University Medical Centre + The Netherlands Food Matters Live, Nov 21-23 rd , London
37
Embed
Exploring the link between gut microbiota and metabolic health · 2017-12-05 · Exploring the link between gut microbiota and metabolic health Ellen Blaak ... obesity and type 2
This document is posted to help you gain knowledge. Please leave a comment to let me know what you think about it! Share it to your friends and learn new things together.
Transcript
Exploring the link between gut microbiota and metabolic health
Ellen Blaak
Professor in Physiology of fat metabolism, Department of Human Biology NUTRIM School of Nutrition and Translational Research in Metabolism
Maastricht University Medical Centre+
The Netherlands
Food Matters Live, Nov 21-23rd, London
Department
Overview
• Modulation of microbiota and metabolic health:
• feces transplantation and antibiotics
• Role of SCFA and metabolic health:
• Colonic SCFA administration
• Intervention with prebiotics-dietary fibers
of Human Biology
Department
Microbiota, obesity and type 2 diabetes mellitus
• Worldwide, obesity is reaching epidemic proportions
• The obesity pandemic is not fully explained by most common gene-environment interactions
• Gut microbiota provide additional gene products that may affect host metabolism, gut physiology, body weight control and insulin sensitivity through several mechanisms
• Obesity and Type 2 diabetes mellitus are associated with differential composition of gut microbiota and/or gut microbiome
• Interventions to manipulate gut-microbiota may favorably affect metabolism and reduce diabesity risk
of Human Biology
Department
Obesity – pandemic of 21st century
Department
Cardiovascular disease Type 2 diabetes Liver steatosis Cancer
OBESITY
of Human Biology
Obesity: an important risk factor for chronic metabolic diseases
Department
Feces transplantation from mice to mice
of Human Biology
Department
From mice to mice: Gut Flora contributes to the high-fat induced metabolic diseases in mice
(Bäckhed et al, 2004, 2007)
Germ-free mice are protected from development of
insulin resistance and glucose intolerance of Human Biology
Department
From man to mice: Gut microbiota from twins discordant
for obesity modulate metabolism in mice
of Human Biology
V K Ridaura et al. Science 2013;341:1241214
Department
From man to man: feces transplantation and human
metabolism
of Human Biology
Department
Department
Transferring microbiota between conventional and germ free rodents, humans and rodents and humans and humans have shown the role of intestinal microbiota in the development of obesity and insulin resistance
of Human Biology
Department of Human Biology
Department
Antibiotics intervention
40-70y
IFG/IGT
HOMA-IR>2.2
n=56
wk 1 pre
wk 2
2d wash out
wk 3 post
wk 8 follow-
up
Treatment Timing
Placebo
Amoxicillin
Vancomycin
1500 mg/day
7 days
of Human Biology Reijnders et al, Cell metabolism, 2016
Department
Microbiota composition
• Vanco:
– Increased gram
negative
Proteobacteria
– less gram-
positive bacteria
– decreased
diversity
– After 8 weeks
similarity with
baseline still
lower, diversity
slightly lower
• Amox:
• no diversity
and/or
composition
differences
Distinct changes in microbiota composition
of Human Biology Reijnders et al, Cell metabolism, 2016
Department
No effect on insulin sensitivity
Two-step hyperinsulinemic-euglycemic clamp
Endogenous Glucose Production
Rate of Disappearance
Suppression of Free Fatty Acids
%
of Human Biology Reijnders et al, Cell metabolism, 2016
No effect on whole body insulin resistance 8 wk after stopping the active intervention
Department
of Human Biology Reijnders et al, Cell metabolism, 2016
Department
Perspectives
• Modulation of adult microbiota by 7-day antibiotics does not affect host metabolism
• Host metabolism remained unchanged at 8-week
follow-up, despite deviant microbiota
• Contradicts many rodents studies!
• More frequent antibiotic use, long term diet effects?
of Human Biology
Department
Function of micrbiota: site of fermentation
proximal colon: primarily saccharolytic
fermentation
transverse colon: combination of saccharolytic and proteolytic fermentation
distal colon: primarily proteolytic fermentation
of Human Biology
Department
Acetate
Propionate
Butyrate
Major SCFA
of Human Biology
Department
Canfora, E. E. et al. (2015) Short-chain fatty acids in control of body weight and insulin sensitivity