The document provides an overview of the human microbiome and its importance. It notes that the human microbiome consists of trillions of microbes, especially bacteria, that inhabit our bodies. Our microbial cells outnumber our human cells 10 to 1. The microbes play an important role in metabolism, immune function, and other processes. Ongoing research is exploring links between the microbiome and conditions like obesity, cancer, inflammatory bowel disease, and neurological disorders. The microbiome represents an exciting area of research into human health and disease.

1. Our bodies,
our microbes,
ourselves
jneufeld@uwaterloo.ca
Extended Learning
Opportunities
Erin, Ontario
Feb 23, 2012
Twitter @JoshDNeufeld

2. Linking function and phylogeny
Stable-isotope probing and metagenomics
Carbon cycling and biofuel bugs
Discovery of novel N-cycle players
Denitrification
Nitrification
Anammox
Diversity of microbial communities
Factors (pH, latitude), human microbiome
Rare members, undetected organisms
Method development

3. Today’s lecture – an overview
Microbial ecology
Why is this so hard to study?
Microbiology of you
What’s in you and why does it matter?

4. Thanks
Handelsman
J.
2007.
Encyclopedia
of
Life
Sciences

5. 1021 Number of stars in the Universe
1031 Number of microbial cells on Earth
1011 Stars in the Milky Way
1015 Microbial cells with each human
1014 Human cells with each human
1010 Microbial cells per gram of soil
106 Microbial cells per mL of seawater
107 Viral particles per mL of seawater
Microbial World

7. I then most always saw,
with great wonder, that in
the said matter there were
h9p://en.wikipedia.org/wiki/Antonie_van_Leeuwenhoek
many very little living
animalcules, very prettily
a-moving.

8. Carl Woese, Professor
of Microbiology at
the University of Illinois
at Urbana-Champaign
One of the first to use
the sequences of
ribosome genes for
taxonomy
Bacterial taxonomy
became “a field fresh
with the excitement of
the experimental
harvest”

9. 16S
rRNA
genes
Why
so
ubiquitous
for
microbial
ecology
studies?
“The
small
subunit
ribosomal
RNA
genes
were
ideal
because
of
their
universal
distribu.on,
structural
conserva.on,
the
presence
of
conserved
and
variable
regions,
and
resistance
to
lateral
gene
transfer”
Neufeld
and
Mohn
(2005)

10. CharacterizaWon
of
microbial
isolates
universal
phylogeneWc
tree
PROKARYOTES
EUKARYOTES
You
Bacteria
Archaea
Eukarya
are
here.
Animals
Entamoebae
Slime
Green nonsulfur molds
bacteria
Euryarchaeota
Fungi
Mitochondrion
Methanosarcina
Methano- Extreme Plants
Gram- Crenarchaeota
bacterium
halophiles
Proteobacteria
positive Thermoproteus
bacteria
Methano- Ciliates
Chloroplast
Pyrodictium
coccus
Thermoplasma
Cyanobacteria
Thermococcus
Flavobacteria
Flagellates
Marine Pyrolobus
Crenarchaeota
Methanopyrus
Trichomonads
Thermotoga
Thermodesulfobacterium Microsporidia
Aquifex Diplomonads
Universal (Giardia)
ancestor

11. Sampling
microbial
communiWes
Sampling
microbial
irds
Costa
Rica
b communiWes
is
akin
to
sampling
diverse
communiWes
from
other
areas
of
biology.
Sampling
is
usually
done
by
capturing
sequences
rather
than
capturing
organisms.
Hughes
et
al.
2001
Problem?

12. Today’s lecture – an overview
Microbial ecology
Why is this so hard to study?
Microbiology of you
What’s in you and why does it matter?

13. Who are we?
What we’ve learned
from ribosomal RNA
surveys of our
bodies and the
environment.
Image
by
Feel
MysWc

14. DISCLAIMER
No medical advice in this talk.

15. There are more bacteria in your gut than
there are people on the planet.

16. 10
ba
cteria
l
cells
:
1
hu
man
c
ell

18. 1 g of feces = 1 million bacteria
Every surface of our body is a
niche for microbes
90% microbe, 10% human
100X more microbial genes
than human genes
Humans are like “spaceships”
for our bugs
Our microbial fingerprint is unique

20. LocaWon,
locaWon,
locaWon
Mouth:
saliva,
tongue,
mucosal
surfaces,
teeth
and
gums
(700
species;
10
phyla)
Esophagus:
microbes
from
oral
cavity
and
upper
respiratory
tract
(95
species;
6
phyla)
Stomach:
low
numbers;
lactobacilli,
streptococci,
H.
pylori
(128
species;
8
phyla)
Small
intes.ne:
-­‐
duodenum:
not
opWmal
to
colonize
-­‐
jejunum:
increase
in
streptococci,
lactobacilli,
Haemophilus,
Bacteroides,
and
Bifidobacteria
-­‐
ileum:
increased
numbers,
resembles
colon
Large
intes.ne
(colon):
-­‐
Lumen:
anaerobes:aerobes
100-­‐1000:1
-­‐
Bacteroides,
Bifido,
Clostridium,
Bacillus,
Fusobacterium
(800
species;
10
phyla)

21. What role do
microorganisms
play in your body?

22. Sterile at birth
Colonization begins
immediately

23. “Adult”
community
by 1 year

26. Peas
and
formula
?
AnWbioWcs
Koeniga
et
al.
2011

29. Mouth
2 3 1 Supragingival plaque L
1 4
2 Subgingival plaque L
3 Supragingival plaque L
4 Supragingival plaque L
5 Tongue biofilm
5
Stomach
6 6 Gastric antrum
7 Gastric body
7 8 Duodenum
8
9 10
Colon
9 Transverse colon
11 10 Sigmoid colon
11 Rectum
12 Stool
12

32. a Tongue plaque Transverse Colon
Sample site Tooth plaque Sigmoid Colon Phylum
PC1 (7.9%)
Gastric antrum Rectum
Gastric body Stool Genus
Duodenum
Faecalibacterium
Bacteroides
Coprococcus Verrucomicrobia
Campylobacter
Blautia
Fusobacterium Bacteriodetes
Fusobacteria
Prevotella Acidobacteria
Cyanobacteria
Firmicutes
Proteobacteria TM7
Neisseria Capnocytophaga
Haemophilus Spirochaetes
Actinobacteria
Streptococcus Veillonella
SR1
Parvimonas
PC1 (17.0%)
b Sample location c Subject d Gender
Mouth
Stomach Subject 1
Duodenum Subject 2 Female
Colon Subject 3 Male
Stool Subject 4

33. Stomach/
Colon
Duodenum
Mouth Stool
173 527
1523 33 578
6567 251
70 18
171
64 69 58
3
112
Subject 1

36. Women
Men

38. Gut
Microbiome
Ley
et
al.
2006
Germ-­‐free
mouse
colonized
with
microbial
community
of
obese
mouse
or
lean
mouse.
Obese
mice
• 50%
lower
Bacteroidetes,
higher
Firmicutes
• Weight
loss
=
increased
Bacteroidetes,
decreased
Firmicutes
Same
result
found
in
humans
(Turnbaugh
et
al.
2006)

40. Depression

41. Behaviour
Premysl
Bercik,
McMaster
University
(personal
communicaWon)

42. “Intestinal dysbiosis might
contribute to psychiatric
disorders in patients with
bowel disorders.”

44. Implications?

45. Probiotics "Live microorganisms which when
administered in adequate amounts confer a health benefit on the host".

46. Fecal
transplants
have
>90%
success
rate
in
C.
difficile
associated
disease.
How
else
could
they
be
used?
"The
potenWal
is
very
high,
but
the
actual
amount
of
research
is
relaWvely
low”
-­‐Rob
Knight
Fecal transplants

48. What will we
discover next?

49. ?

50. ?

51. ?

52. ?

53. ?

54. ?

55. ?

56. ?

57. Gut
Microbiome
summary
Over
800
different
species,
7000
strains
Experimental
evidence
shows
implicaWons
in:
• metabolism
of
carbohydrates
(obesity)
• ulcers
and
Helicobacter
pylori
predominance
• immune
system
(allergies,
asthma,
pathogen
defense)
• synthesis
of
amino
acids
and
vitamins
• deacWvaWng
xenobioWcs
(carcinogens)
• response
to
epithelial
cell
injury
(by
pathogens)
• colorectal
cancer
(2nd
leading
cause
of
cancer-­‐related
death)
• inflammatory
bowel
diseases
(Crohn’s
and
coliWs)
• possible
role
in
mulWple
sclerosis,
Parkinson’s
• link
to
depression
and
behaviour

58. Research
in
my
lab
seeks
to
answer
some
of
these
quesWons
IBS,
depression,
periodonWWs
Turnbaugh
et
al.
2007

59. Hygiene
hypothesis

62. "The human microbiome has been selected,
and passed from mother to child, because the
bacterial genes are helpful, but as a result of
modern practices including widespread
antibiotics use, caesarean sections, amalgam
dental fillings, constant cleansing, clean water,
smaller families and transmission of these
normal ancestral microbes has changed, and
there are consequences. Some consequences
might be good, while others could be bad."
Dr. Martin J. Blaser
Professor of Microbiology
NYU Langone Medical Center

63. Implications
Health and disease linked to microbes
Novel treatments can come from microbes
With understanding, we can be in control
What’s next? (invite your help)

65. Thank you
jneufeld@uwaterloo.ca
Extended Learning
Opportunities
Erin, Ontario
Feb 23, 2012
Twitter @JoshDNeufeld