Cross-talks between gut microbiome &
the host physiology metabolic health
European OneHealth/EcoHealth Workshop
Plovier Hubert
Pr. Patrice D. Cani’s Lab
Gut microbes and the metabolic syndrome
Which one triggers the other ? A “Chicken or the egg?” - like dilemma
• Alterations during obesity
Control diet
Diet-induced obesity
– Composition
– Activity
• Causative agent
– Transfer of obese
microbiota increases fat
mass gain
– Metabolic endotoxemia
initiates insulin resistance
Cani P.D. et al., Diabetes, 2007
Ridaura V. et al., Science, 2013
Everard A. et al., ISME J., 2014
Bacteroidetes
Firmicutes
Tenericutes
Deferribacteres
Proteobacteria
Verrucomicrobia
Cyanobacteria
Microbe-host interaction: Akkermansia muciniphila
Abundance of A. muciniphila varies in pathophysiological conditions
• Lower abundance during
obesity
– Genetic and diet-induced
– Drastic diminution
• Administration decreases
diet-induced obesity
– Fat mass gain
– Glucose metabolism
Everard A. et al., PNAS, 2013
Microbe-host interaction: Akkermansia muciniphila
Preclinical evidence indicates that A. muciniphila acts on various organs
 Mucus layer thickness
 Antimicrobial peptides
 Specific bioactive lipids
 Metabolic endotoxemia
 Cholesterol
 Triglycerides
Plovier H. et al., unpublished data
Everard A. et al., PNAS, 2013
 Insulin sensitivity
 Glucose production
 Oxidation
 Fat mass
 Inflammation
Microbe-host interaction: Akkermansia muciniphila
Dietary interventions can increase A. muciniphila abundance
• Prebiotics
• Polyphenols
• Fish oil
Everard A. et al., PNAS, 2013
Caesar R. et al., Cell Metab., 2015
Microbe-host interaction: Akkermansia muciniphila
Metformin increases Akkermansia abundance and improves gut barrier
Shin N.R.. et al., Gut, 2014
Microbe-host interaction: Akkermansia muciniphila
Of mice and men – Clinical data corroborate observations in mice
 A. muciniphila
Le Chaterlier E. et al., Nature, 2013
 A. muciniphila
Zhang H. et al., PNAS, 2009
Liou A.P. et al., Sci. Transl. Med., 2013
Dao M.C, Everard A., … Cani P.D. & Clément K, Gut, 2016
Wang L. et al., AEM, 2011
Microbe-host interaction: Akkermansia muciniphila
Of mice and men – Clinical data corroborate observations in mice
Forslund K. et al., Nature, 2015
Microbe-host interaction: Akkermansia muciniphila
Assessing A. muciniphila clinical potential: the Microbes4U study
100 subjects
BMI ≥ 25, insulin resistance and metabolic syndrome
Randomized, single-blind, parallel, placebo-controlled
NCT02637115
3 months of treatment
Placebo
Randomization
Live A. muciniphila (1010 CFU/day)
Informed
consent
Live A. muciniphila (109 CFU/day)
Inactivated A. muciniphila
15 days
Safety check
Key Outcomes: body weight, insulin resistance, type-2 diabetes, dyslipidemia,
inflammation, gut microbiota, gut barrier function
ERC-PoC-2016
Conclusion
Time to put the microbiota at work for the management of obesity
• Gut microbes and the
metabolism of their host are
deeply intertwined
• Specific microbes can have a
tremendous influence on the
host physiology
– Cross-talks with the immune
system
• Probiotics-based strategies can
add to the therapeutic arsenal
against the metabolic
syndrome
ERC-StG-ENIGMO-2013
And
ERC-PoC-Microbes4U-2016
Walloon Excellence in
Life Sciences and BIOtechnology
INSERM, Toulouse,
France
Prof C. Knauf
Prof. R. Burcelin
LDRI, UCL, Belgium
Prof G. Muccioli
DDUV, UCL, Belgium
Prof JB Demoulin, Dr A. Essaghir
Prof JC Renauld, Prof. L Dumoutier
IREC
Prof Y. Guiot
Rose-Marie Gobbels
Paris Diderot University Université de Genève,
Hopitaux universitaires
Dr S. Luquet
Prof J. Schrenzel
Prof. C. Magnan
Prof P. François
Paris Curie Institute
Prof V. Lazarevic
Prof S. Robine
KULeuven
Prof. S.W. van der Werve
Prof. J. van Pelt
Wageningen UR
Prof W. de Vos
Dr M. Derrien
Dr. C. Belzer
Dr. J Ouwerkerk
Pitié-Salpêtrière hospital
ICAN
Prof K. Clément
Dr Dao and Microbes
consortium
Metabolomic and Molecular Image
Lab, INCLIVA, Valencia, Spain
Prof. D. Monleon and his team
Gothenburg University, Sweden
Prof F. Backhed
Dr. R. Caesar
Dr. M. Stahlman
Dr. M. Johansson
Former members of Cani’s team
Dr. M. Osto, F. Pierard, M. Van Roye
O. Rottier, Dr. S. Matamoros, Dr. T.
Duparc, A. Bever, Dr G. Trinchese
IDIBAPS and CIBERDEM,
Barcelona, Spain
Dr M. Claret and his team