BIS2C: Lecture 13: The Human Microbiome

Slides by Jonathan Eisen for BIS2C at UC Davis Spring 2016
Lecture 13:
The Human Microbiome
BIS 002C
Biodiversity & the Tree of Life
Spring 2016
Prof. Jonathan Eisen
1

Where we are going and where we have been
• Previous Lecture:
!12: Novelty
• Current Lecture:
!13: The Human Microbiome
• Next Lecture:
!14: Big Organisms
2

Key Concepts and Outline
• Humans are swarming with microbes
• Microbiomes are Complex Ecosystems
• Enormous Variation within & between
People
• Variation is Associated with Various Health
States and Phenotypes
• Possible Causes of the Variation Have
Been Identified
• It May Be Possible to Alter / Restore the
Microbiome
4

Classes of symbiosis
Organism
Class of symbiosis A B
Mutualism + +
Commensalism + 0
Parasitism + -
5

Organism
Mutualism + +
Commensalism + 0
Parasitism + -
6

7

Summer 2012 Workshop in Biology and
Multimedia for High School Teachers
Microbes are all over us
8
http://commons.wikimedia.org/wiki/
File:Man_shadow_-_upper.png
Thousands of different species on the skin alone
Some thrive on dry patches of the elbow, others
thrive in moist environment of armpit
There are millions of microbes
per square inch on your body
It is estimated that there are more microbes
in your intestine than there are human cells
in your body!

Who Are We?
9

Who Are We?
10
50

microBIOME or microbiOME
• microbi-OME
!collection of genomes of microbes from a
community (emphasis on OME)
• micro-BIOME
!a community of microbes (emphasis on
BIOME)
• see http://tinyurl.com/definemicrobiome
11

Clicker
12

Clicker
Which of the following lineages contain
microbes?
A: Bacteria
B: Archaea
C: Eukaryotes
D: All of the above
E: None of the above
13

Clicker
Which of the following lineages contain
microbes?
A: Bacteria
B: Archaea
C: Eukaryotes
D: All of the above
E: None of the above
14

The Rise of the Microbiome
15
0
350
700
1050
1400
00 01 02 03 04 05 06 07 08 09 10 11 12
Pubmed “Microbiome” Hits

Organism
Mutualism + +
Commensalism + 0
Parasitism + -
16
Why All The Attention for Commensalism?

Organism
Mutualism + +
Commensalism + 0
Parasitism + -
17
Is this Mutualism?

Organism
Mutualism + +
Commensalism + 0
Parasitism + -
18
Is this Parasitism?

Organism
Mutualism + +
Commensalism + 0
Parasitism + -
19
Some of Each

Why Now? Studies Like This …
20
Turnbaugh et al Nature. 2006 444(7122):1027-31.

Microbiome Involved in Many Functions
• Digestion
• Vitamin Production
• Protection from parasites / pathogens
• Metabolic rate
• Immune regulation
• Odor
• Behavior
21

Slides by Jonathan Eisen for BIS2C at UC Davis Spring 2016 22
Why Now II: DNA Sequencing Advances

Great Plate Count Anomaly
23
<<<<
Culturing Observation
CountCount
http://www.google.com/url?
sa=i&rct=j&q=&esrc=s&source=images&c
d=&docid=rLu5sL207WlE1M&tbnid=CRLQ
YP7d9d_TcM:&ved=0CAUQjRw&url=http
%3A%2F%2Fwww.biol.unt.edu
%2F~jajohnson
%2FDNA_sequencing_process&ei=hFu7U_
TyCtOqsQSu9YGwBg&psig=AFQjCNG-8EB
dEljE7-
yHFG2KPuBZt8kIPw&ust=14048739512114
24
DNA 
or
RNA

Archaea
Woese Classification of Cultured Taxa by rRNA
24
rRNA rRNArRNA
ACUGC
ACCUAU
CGUUCG
ACUCC
AGCUAU
CGAUCG
ACCCC
AGCUCU
CGCUCG
Taxa Characters
S ACUGCACCUAUCGUUCG
R ACUCCACCUAUCGUUCG
E ACUCCAGCUAUCGAUCG
F ACUCCAGGUAUCGAUCG
C ACCCCAGCUCUCGCUCG
W ACCCCAGCUCUGGCUCG
EukaryotesBacteria
Carl
Woese

rRNA
Taxa Characters
B1 ACTGCACCTATCGTTCG
B2 ACTCCACCTATCGTTCG
E1 ACTCCAGCTATCGATCG
E2 ACTCCAGGTATCGATCG
A1 ACCCCAGCTCTCGCTCG
A2 ACCCCAGCTCTGGCTCG
New ACCCCAGCTCTGCCTCG
EukaryotesBacteria Archaea
Culture Independent Studies
ACTGC
ACCTAT
CGTTCG
ACTGC
ACCTAT
CGTTCG
ACTGC
ACCTAT
CGTTCG
Many
sequences
from one
sample all
point to the
same branch
on the tree
Norm
Pace

DNA
Taxa Characters
B1 ACTGCACCTATCGTTCG
B2 ACTCCACCTATCGTTCG
E1 ACTCCAGCTATCGATCG
E2 ACTCCAGGTATCGATCG
A1 ACCCCAGCTCTCGCTCG
A2 ACCCCAGCTCTGGCTCG
New1 ACCCCAGCTCTGCCTCG
New2 AGGGGAGCTCTGCCTCG
New3 ACTCCAGCTATCGATCG
New4 ACTGCACCTATCGTTCG
EukaryotesBacteria Archaea
ACTGC
ACCTAT
CGTTCG
ACTCC
AGCTAT
CGATCG
ACCCC
AGCTCT
CGCTCG
AGGGG
AGCTCT
CGCTCG
AGGGG
AGCTCT
CGCTCG
ACTGC
ACCTAT
CGTTCG
Even with
more taxa it
still works
Culture Independent Studies

Metagenomics Has Many Other Purposes
27
metagenomics
ACUGC
ACCUAU
CGUUCG
ACUCC
AGCUAU
CGAUCG
ACCCC
AGCUCU
CGCUCG
Taxa Characters
S ACUGCACCUAUCGUUCG
R ACUCCACCUAUCGUUCG
E ACUCCAGCUAUCGAUCG
F ACUCCAGGUAUCGAUCG
C ACCCCAGCUCUCGCUCG
W ACCCCAGCUCUGGCUCG
inputs of fixed carbon or nitrogen from external sources. As with
Leptospirillum group I, both Leptospirillum group II and III have the
genes needed to fix carbon by means of the Calvin–Benson–
Bassham cycle (using type II ribulose 1,5-bisphosphate carboxy-
lase–oxygenase). All genomes recovered from the AMD system
contain formate hydrogenlyase complexes. These, in combination
with carbon monoxide dehydrogenase, may be used for carbon
fixation via the reductive acetyl coenzyme A (acetyl-CoA) pathway
by some, or all, organisms. Given the large number of ABC-type
sugar and amino acid transporters encoded in the Ferroplasma type
Figure 4 Cell metabolic cartoons constructed from the annotation of 2,180 ORFs
identified in the Leptospirillum group II genome (63% with putative assigned function) and
1,931 ORFs in the Ferroplasma type II genome (58% with assigned function). The cell
cartoons are shown within a biofilm that is attached to the surface of an acid mine
drainage stream (viewed in cross-section). Tight coupling between ferrous iron oxidation,
pyrite dissolution and acid generation is indicated. Rubisco, ribulose 1,5-bisphosphate
carboxylase–oxygenase. THF, tetrahydrofolate.
articles
NATURE | doi:10.1038/nature02340 | www.nature.com/nature 5©2004 NaturePublishing Group

Clicker
28

Clicker
How could you tell if one of the rRNA genes
you sequence came from a chloroplast?
A: It should group in rRNA trees with plant
nuclear rRNA genes.
B: It should group in rRNA trees with
proteobacteria.
C: It should group in rRNA trees with
cyanobacteria.
D. It should group in rRNA trees with TACK
E: You can’t tell.
29

Clicker
you sequence came from a chloroplast?
A: It should group in rRNA trees with plant
nuclear rRNA genes.
B: It should group in rRNA trees with
proteobacteria.
C: It should group in rRNA trees with
cyanobacteria.
D. It should group in rRNA trees with TACK
E: You can’t tell.
30

you sequence came from a mitochondrion?
31

you sequence came from a fungus?
32

People
Been Identified
Microbiome
33

34

People
Been Identified
Microbiome
36

Variation Between Countries: Gut
40
The ISME Journal (2013) 7, 85–95; doi:10.1038/ismej.2012.81
MJ Blaser et al. ISMEJ 2012
US Amerindian
Actinobacteria
(Propionibacteria)
Firmicutes
(Staphylococcus)
Relativeabundance
Actinobacteria dominates in the US
Boulder NY Platanillal A Platanillal B
Proteobacteria

Variation Between Countries: Gut
41
The ISME Journal (2013) 7, 85–95; doi:10.1038/ismej.2012.81
MJ Blaser et al. ISMEJ 2012
US Amerindian
Actinobacteria
(Propionibacteria)
Firmicutes
(Staphylococcus)
Relativeabundance
Actinobacteria dominates in the US
Boulder NY Platanillal A Platanillal B
Proteobacteria

Variability Across People
42Huttenhower et al. 2012.

People
Been Identified
Microbiome
43

Variability is Correlated to Many Health States
• Microbial community different in many disease
states compared to healthy individuals
• Unclear if this is cause or effect in most cases
44

!45
Morgan et al. Genome Biology 2012 13:R79 doi:10.1186/gb-2012-13-9-r79

!46
Morgan et al. Genome Biology 2012 13:R79 doi:10.1186/gb-2012-13-9-r79
Age Diet Location
Many disease states
ExposurePregnant?
Breast fed? Obese

Microbiome Involved in Many Functions
• Digestion
• Vitamin Production
• Protection from parasites / pathogens
• Metabolic rate
• Immune regulation
• Odor
• Behavior
47

People
Been Identified
Microbiome
48

Infant Microbiome, Birth, and Milk
49
David Mills

Other Sources
50

Disturbing the Microbiome
51
Antibiotics
Diet Changes
Hygiene
Hypothesis
C-sections

C-Sections Alter “Normal” Colonization
52
Maria Gloria
Dominguez-Bello

Diet Changes Alter Microbiome
53
Switch to solid foods

Response to Antibiotics
54
illustrated by the communities of subjects 14, 15, 16, 18, and 19 that
appeared to be comparatively stable over time, whereas others such as
subjects 11 and 27 commonly shifted to different community types that
were more often associated with higher Nugent scores. The underlying
The rapid and sometimes extensive turnover of human vaginal bacte-
rial communities was visualized by mapping temporal changes in
community composition onto the three-dimensional (3D) community
space defined previously in a cross-sectional study by Ravel et al. of
A B
DC
Subject 24
0
20
40
60
80
100
Phylotyperelativeabundance(%)
L. crispatus
L. iners
L. jensenii
Staphylococcus
L. gasseri
Corynebacterium
Clostridium
Lactobacillales 2
L. vaginalis
L. otu5
Subject 29
0
20
40
60
80
100
Subject 6
0
20
40
60
80
100
L. iners
Atopobium
Sneathia
Corynebacterium
Gemella
Finegoldia
Prevotella
Peptostreptococcus
Peptoniphilus
Anaerococcus
Streptococcus
Parvimonas
Staphylococcus
Subject 12
0
20
40
60
80
100
Time (weeks)
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15
Time (weeks)
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15
Time (weeks)
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15
Time (weeks)
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15
Phylotypes
L. crispatus L. iners L. gasseri StaphylococcusL. jensenii Atopobium
Prevotella
Aerococcus
Anaerococcus
Streptococcus
Clostridium
ParvimonasGardnerella Mobiluncus Corynebacterium
Gemella
Finegoldia Peptostreptococcus Peptoniphilus
L. otu5Lactobacillales 2 L. otu3 L. vaginalis L. otu4Sneathia 80 100
Phylotype percent
relative abundance
0 20 40 60
L. crispatus
Streptococcus
L. reuteri
Bifidobacterium
Anaerococcus
Prevotella
Finegoldia
Peptostreptococcus
Escherichia
Alloscardovia
Atopobium
Prevotella
Parvimonas
Peptoniphilus
Sneathia
Mobiluncus
Lachnospiraceae 10
Ruminococcaceae 3
Gardnerella
Lachnospiraceae 11
Aerococcus
Moryella
Peptococcus
Lachnospiraceae 2
Anaerococcus
Allisonella
Peptostreptococcus
Megasphaera
Lachnospiraceae 10 Ruminococcaceae 3
Lachnospiraceae 11Moryella PeptococcusLachnospiraceae 2
Allisonella
Megasphaera
L. reuteri Bifidobacterium
Escherichia Alloscardovia
onMay2,2012stm.sciencemag.orgDownloadedfrom

Hygiene Hypothesis
55
Susan Lynch
Dogs, Dust, Microbiomes and Asthma

People
Been Identified
Microbiome
56

Microbiome Transplant
57

Restoring the Microbiome: Probiotics and Prebiotics
58

Intestinal Transplant
59
Hartman et al. PNAS 2009

Coprophagia
60

Transfaunation
61

Fecal “transplants”
62

Openbiome
63

DIY Fecal Transplant
64

DIY Fecal Transplant

Get Involved
67
Kitty Microbiome

BIS2C: Lecture 13: The Human Microbiome

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