microbiome: why a few trillion germs can be a good thing
TRANSCRIPT
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Microbiome: Why a few trillion germs can be a good thing
Paul KubesProfessor
Director Snyder Institute for Chronic Diseases
Dept of Physiology & Pharmacology,
Cumming School of Medicine
Kathy McCoyProfessor
Director - Western Canadian Microbiome Germ-Free Program
Dept of Physiology & Pharmacology,
Cumming School of Medicine
April 18, 2017
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Paul KubesDepartment of Physiology & Pharmacology
Professor at the University of Calgary and Founding Director of the Snyder Institute for Chronic Diseases
Canada Research Chair in Leukocyte Recruitment in Inflammatory Disease
Research focus on understanding complex immune responses in the context of human clinical disease and imaging immune cells during Inflammation, Infection and tissue Injury
Canada’s Health Researcher of the year in 2011
Published >300 papers in top scientific journals
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Kathy McCoyDepartment of Physiology & Pharmacology
Professor at the University of Calgary and Founding Director of the Western Canadian Microbiome Germ-free Program
PhD from Malaghan Institute for Medical Research and Otago University, New Zealand
Research focus on understanding the role of the microbiome in immunity, especially in early life
Published >80 papers in top scientific journals
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Because we are still at WAR in 2014!
CHARLES REX ARBOGAST / THE ASSOCIATED PRESS
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Antibiotic resistant microorganisms
Vancomycin-Resistant
Enterococcus
VRE
How close are we to a nightmarish
return to a pre-antibiotic era?
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The Neutrophil – The Policeman
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Bacteria
Most people think of bacteria as germs that make you sick, but in fact they are also critical to keeping you healthy
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Microbiome
• Collection of bacteria living in and on your body or those living in a particular environment
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The human microbiome
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What are microbes?
• A “microscopic organism,” is a living thing too small to be seen with the naked eye
• Usually only one cell organism
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Key definitions
Microbiota: a community of microbes
Microbiome: really refers to all the microbial genes
Microbe:• Bacteria: single cell organism usually what we look at in
microbiome• Stapholococcus• Streptococcus• E.coli
• Fungi• Virus• Amoeba
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Bacteria
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Fungi
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Virus
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Amoeba
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Diversity increases with age
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Microbiome and health
Even your two hands have different microbiomes!
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Microbiome and health
You’re surrounded by a cloud of bacteria as unique as a fingerprint
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Pigpen was not the only one!
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You and your spouse share microbiome
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Your microbiome starts at birth
• Vaginal birth begets different microbiome than Cesarean section (mostly skin) often of the doctor or nurse
• At home birth different than at hospital
• Breast milk versus formula
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Influenced by diet
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Genetics & disease
Our genes have not changed over last 30 years
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Environment & disease
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Environment & disease
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Environment & disease
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Environment & disease
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Environment & disease
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Environment & disease
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What has changed?
Then
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What has changed?
Now
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Hygiene hypothesis
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Antibiotics alter your microbiome
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Antibiotics
It could take years to replenish a normal gut microbiome
Antibiotics no longer recommended
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Antibiotics
Antibiotics can affect mom’s microbiome and its transfer to baby
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Microbiome links to chronic diseases
◾Acne- teenage change in oils- P. acnes◾Eczema◾Asthma/allergies
◾Autism- often have GI disorders◾Depression and anxiety (metabolites)
◾Autoimmune diseases- RA, MS◾Inflammatory bowel diseases◾Gastric ulcers- H. pylori◾Cancer- H. pylori, viruses
◾Hardening of the arteries- gum disease, infected◾Malnutrition- bacteria help absorb nutrients ◾Obesity- microbiome transfers, change weight◾Diabetes- Type II- switch microbiome◾Dental cavities- Bacteria make acid
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Antibiotics
Antibiotics save lives but need to be given appropriately
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Takeaways
• Not all bacteria are bad
• There is a new organ: the microbiome
• Affecting the microbiome can affect our health
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Man & microbe: A superorganism
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All mucosal surfaces are home to microbiota
• All mucosal surfaces are colonized with bacteria
• Different mucosal surfaces are home to different diversities and composition
Cho & Blaser, Nature Reviews Immunology 2012
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All mucosal surfaces are home to microbiota
• The intestine is a preferred site
• >70% of all bacteria are found in the large intestine (colon)
• >70% of all immune cells are found in the intestine
Sekirov et al, Physiol Reviews 2010
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Colonization occurs in the first years of life
• Born germ-free
• Increasing numbers & increasing diversity within first year
• Heavily influenced by maternal colonization, environmental exposures, diet, antibiotics
McCoy & Köller Clinical Immunology 2015
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Development of immune system
• Immune system of a newborn is not fully developed
• Requires signals from the microbiota for normal development
• ‘Missing’ microbiota at an important time during immune development could increase diseases susceptibility
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Critical window
Early life colonization coincides with a time-limited period in which the immune system is permissive to education from the microbiota
Proper/improper immune education during critical window impacts on resistance/susceptibility to disease later in life
Birth
Prenatal Neonatal AdultYoung
Microbial diversity
Critical Window
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Microbial colonization during critical window
• Gut
• Lung
• Skin
AllergyIBD
Asthma
Atopic dermatitisPsoriasis
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Is the maternal microbiota important?
Exposure to antibiotics during pregnancy is associated with increased susceptibility of infant to immune-mediated diseases
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Maternal microbiota effects
Birth
Prenatal Neonatal AdultYoung
Microbial diversity
Critical Window
Exposure to live intestinal microbes
Exposure to microbial products/metabolites
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Gestational-ONLY colonization
Birth
Prenatal Neonatal AdultYoung
TransientMicrobial colonization
Baby
Microbial colonization
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Gestational-ONLY colonization
Birth
Prenatal Neonatal AdultYoung
TransientMicrobial colonization
Baby
Microbial colonization
• Molecules (metabolites) originating from the maternal microbiota are transferred to the baby through the placenta and the milk
• These molecules stimulate development of innate immune cells in the offspring
• Maternal microbiota prepares the newborn to accept its own microbiota after birth without developing inflammation
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Thanks Mom!
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Strengthen your immune system & don’t destroy your microbiome
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How to harness the power of the microbiome?
FMT:
Fecal microbial transplantation
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Western Canadian Microbiome Centre (WCMC)
WCMC Platforms• Germ free• Genomics & Bioinformatics• Proteomics/Metabolomics• Cytometry• Imaging (in vitro & in vivo)• BioBanking
WCMC Priorities• Platforms• Collaborations• Partnerships• Communication• Education
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WCMC One-stop shop for Microbiome Research
WCMC
Metabolomics
Platform
WCMC
BioBanking
Platform
WCMC
Cytometry
Platform
WCMC
Genomics
Platform
WCMC
Bioinformatics
Platform
WCMC
Imaging
Platform
WCMC Germ
Free Platform
F4/80 Ly6C CD11c
MHC-I MHC-II
CD206
CD11b Ly6G
Kupffer cells (F4/80+ CD11b+ Ly6Clo MHCII+ )
Dcs (CD11c+ F4/80-)
plasmacytoid Dcs (CD11c+ CD317+ F4/80-)
granulocytes (F4/80- Ly6G+ CD24-/low)
Dcs (CD11c+ F4/80-)
unidentified population
unidentified population
infiltrating monocytes (F4/80+ Ly6C+)
granulocytes (F4/80+ Ly6G+ CD24+) 1
2
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basophils (FceR1+ CD11b+ CD44+) 10
infiltrating monocytes (F4/80- CD11clo Ly6C+)
Kupffer cells (F4/80+ CD11c+ CD11b+ Ly6Clo MHCII+ )
a
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Fig.1
F4/80 Ly6C CD11c
MHC-I MHC-II
CD206
CD11b Ly6G
Kupffer cells (F4/80+ CD11b+ Ly6Clo MHCII+ )
Dcs (CD11c+ F4/80-)
plasmacytoid Dcs (CD11c+ CD317+ F4/80-)
granulocytes (F4/80- Ly6G+ CD24-/low)
Dcs (CD11c+ F4/80-)
unidentified population
unidentified population
infiltrating monocytes (F4/80+ Ly6C+)
granulocytes (F4/80+ Ly6G+ CD24+) 1
2
3
4
5
6
7
8
9
11
12
basophils (FceR1+ CD11b+ CD44+) 10
infiltrating monocytes (F4/80- CD11clo Ly6C+)
Kupffer cells (F4/80+ CD11c+ CD11b+ Ly6Clo MHCII+ )
a
b
Sinusoidal zone
Pericentral zone F4
/80
C
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CR
1
CD
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CA
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extravascular
c d
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200
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Fig.1
Gomez de Agüero et al, Science 2016
Li & Limenitakis et al, Nature Communications 2015
Geuking et al, Immunity 2011
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Key takeaways
We may set our microbiome early in life
Excessive antibiotic use will alter your microbiome and therefore impact your health
We need more evidence to support prebiotic and probiotic use
Microbiome transplantation does work in some situations, will be developed further!
www.lettemheatdirt.com
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