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
Slides by Jonathan Eisen for BIS2C at UC Davis Spring 2016
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
Slides by Jonathan Eisen for BIS2C at UC Davis Spring 2016
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
Slides by Jonathan Eisen for BIS2C at UC Davis Spring 2014
Classes of symbiosis
Organism
Class of symbiosis A B
Mutualism + +
Commensalism + 0
Parasitism + -
5
Slides by Jonathan Eisen for BIS2C at UC Davis Spring 2014
Classes of symbiosis
Organism
Class of symbiosis A B
Mutualism + +
Commensalism + 0
Parasitism + -
6
Slides by Jonathan Eisen for BIS2C at UC Davis Spring 2014
The Human Microbiome
7
Slides by Jonathan Eisen for BIS2C at UC Davis Spring 2016
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!
Slides by Jonathan Eisen for BIS2C at UC Davis Spring 2014
Who Are We?
9
Slides by Jonathan Eisen for BIS2C at UC Davis Spring 2014
Who Are We?
10
50
Slides by Jonathan Eisen for BIS2C at UC Davis Spring 2016
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
Slides by Jonathan Eisen for BIS2C at UC Davis Spring 2016
Clicker
12
Slides by Jonathan Eisen for BIS2C at UC Davis Spring 2016
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
Slides by Jonathan Eisen for BIS2C at UC Davis Spring 2016
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
Slides by Jonathan Eisen for BIS2C at UC Davis Spring 2014
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
Slides by Jonathan Eisen for BIS2C at UC Davis Spring 2014
Classes of symbiosis
Organism
Class of symbiosis A B
Mutualism + +
Commensalism + 0
Parasitism + -
16
Why All The Attention for Commensalism?
Slides by Jonathan Eisen for BIS2C at UC Davis Spring 2014
Classes of symbiosis
Organism
Class of symbiosis A B
Mutualism + +
Commensalism + 0
Parasitism + -
17
Is this Mutualism?
Slides by Jonathan Eisen for BIS2C at UC Davis Spring 2014
Classes of symbiosis
Organism
Class of symbiosis A B
Mutualism + +
Commensalism + 0
Parasitism + -
18
Is this Parasitism?
Slides by Jonathan Eisen for BIS2C at UC Davis Spring 2014
Classes of symbiosis
Organism
Class of symbiosis A B
Mutualism + +
Commensalism + 0
Parasitism + -
19
Some of Each
Slides by Jonathan Eisen for BIS2C at UC Davis Spring 2016
Why Now? Studies Like This …
20
Turnbaugh et al Nature. 2006 444(7122):1027-31.
Slides by Jonathan Eisen for BIS2C at UC Davis Spring 2014
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
Slides by Jonathan Eisen for BIS2C at UC Davis Spring 2016
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
Slides by Jonathan Eisen for BIS2C at UC Davis Spring 2016
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
Slides by Jonathan Eisen for BIS2C at UC Davis Spring 2014 25
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
Slides by Jonathan Eisen for BIS2C at UC Davis Spring 2014 26
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
Slides by Jonathan Eisen for BIS2C at UC Davis Spring 2016
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
Slides by Jonathan Eisen for BIS2C at UC Davis Spring 2014
Clicker
28
Slides by Jonathan Eisen for BIS2C at UC Davis Spring 2014
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
Slides by Jonathan Eisen for BIS2C at UC Davis Spring 2014
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.
30
Slides by Jonathan Eisen for BIS2C at UC Davis Spring 2014
How could you tell if one of the rRNA genes
you sequence came from a mitochondrion?
31
Slides by Jonathan Eisen for BIS2C at UC Davis Spring 2014
How could you tell if one of the rRNA genes
you sequence came from a fungus?
32
Slides by Jonathan Eisen for BIS2C at UC Davis Spring 2016
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
33
Slides by Jonathan Eisen for BIS2C at UC Davis Spring 2014
The Human Microbiome
34
Microbiomes as Ecosystems
!35
Slides by Jonathan Eisen for BIS2C at UC Davis Spring 2016
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
36
Slides by Jonathan Eisen for BIS2C at UC Davis Spring 2014 37
Slides by Jonathan Eisen for BIS2C at UC Davis Spring 2014 38
Slides by Jonathan Eisen for BIS2C at UC Davis Spring 2014 39
Slides by Jonathan Eisen for BIS2C at UC Davis Spring 2014
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
Slides by Jonathan Eisen for BIS2C at UC Davis Spring 2014
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
Slides by Jonathan Eisen for BIS2C at UC Davis Spring 2014
Variability Across People
42Huttenhower et al. 2012.
Slides by Jonathan Eisen for BIS2C at UC Davis Spring 2016
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
43
Slides by Jonathan Eisen for BIS2C at UC Davis Spring 2014
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
Slides by Jonathan Eisen for BIS2C at UC Davis Spring 2014
Microbiome Involved in Many Functions
• Digestion
• Vitamin Production
• Protection from parasites / pathogens
• Metabolic rate
• Immune regulation
• Odor
• Behavior
47
Slides by Jonathan Eisen for BIS2C at UC Davis Spring 2016
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
48
Slides by Jonathan Eisen for BIS2C at UC Davis Spring 2014
Infant Microbiome, Birth, and Milk
49
David Mills
Slides by Jonathan Eisen for BIS2C at UC Davis Spring 2014
Other Sources
50
Slides by Jonathan Eisen for BIS2C at UC Davis Spring 2014
Disturbing the Microbiome
51
Antibiotics
Diet Changes
Hygiene
Hypothesis
C-sections
Slides by Jonathan Eisen for BIS2C at UC Davis Spring 2014
C-Sections Alter “Normal” Colonization
52
Maria Gloria
Dominguez-Bello
Slides by Jonathan Eisen for BIS2C at UC Davis Spring 2016
Diet Changes Alter Microbiome
53
Switch to solid foods
Slides by Jonathan Eisen for BIS2C at UC Davis Spring 2014
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
Phylotyperelativeabundance(%)
Subject 6
0
20
40
60
80
100
Phylotyperelativeabundance(%)
L. iners
Atopobium
Sneathia
Corynebacterium
Gemella
Finegoldia
Prevotella
Peptostreptococcus
Peptoniphilus
Anaerococcus
Streptococcus
Parvimonas
Staphylococcus
Subject 12
0
20
40
60
80
100
Phylotyperelativeabundance(%)
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
Slides by Jonathan Eisen for BIS2C at UC Davis Spring 2014
Hygiene Hypothesis
55
Susan Lynch
Dogs, Dust, Microbiomes and Asthma
Slides by Jonathan Eisen for BIS2C at UC Davis Spring 2016
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
56
Slides by Jonathan Eisen for BIS2C at UC Davis Spring 2014
Microbiome Transplant
57
Slides by Jonathan Eisen for BIS2C at UC Davis Spring 2014
Restoring the Microbiome: Probiotics and Prebiotics
58
Slides by Jonathan Eisen for BIS2C at UC Davis Spring 2014
Intestinal Transplant
59
Hartman et al. PNAS 2009
Slides by Jonathan Eisen for BIS2C at UC Davis Spring 2014
Coprophagia
60
Slides by Jonathan Eisen for BIS2C at UC Davis Spring 2014
Transfaunation
61
Slides by Jonathan Eisen for BIS2C at UC Davis Spring 2014
Fecal “transplants”
62
Slides by Jonathan Eisen for BIS2C at UC Davis Spring 2014
Openbiome
63
Slides by Jonathan Eisen for BIS2C at UC Davis Spring 2014
DIY Fecal Transplant
64
Slides by Jonathan Eisen for BIS2C at UC Davis Spring 2014 65
DIY Fecal Transplant
Slides by Jonathan Eisen for BIS2C at UC Davis Spring 2014 66
Slides by Jonathan Eisen for BIS2C at UC Davis Spring 2014 66
Slides by Jonathan Eisen for BIS2C at UC Davis Spring 2016
Get Involved
67
Kitty Microbiome

BIS2C: Lecture 13: The Human Microbiome

  • 1.
    Slides by JonathanEisen 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
  • 2.
    Slides by JonathanEisen for BIS2C at UC Davis Spring 2016 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
  • 3.
    Slides by JonathanEisen for BIS2C at UC Davis Spring 2016 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
  • 4.
    Slides by JonathanEisen for BIS2C at UC Davis Spring 2014 Classes of symbiosis Organism Class of symbiosis A B Mutualism + + Commensalism + 0 Parasitism + - 5
  • 5.
    Slides by JonathanEisen for BIS2C at UC Davis Spring 2014 Classes of symbiosis Organism Class of symbiosis A B Mutualism + + Commensalism + 0 Parasitism + - 6
  • 6.
    Slides by JonathanEisen for BIS2C at UC Davis Spring 2014 The Human Microbiome 7
  • 7.
    Slides by JonathanEisen for BIS2C at UC Davis Spring 2016 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!
  • 8.
    Slides by JonathanEisen for BIS2C at UC Davis Spring 2014 Who Are We? 9
  • 9.
    Slides by JonathanEisen for BIS2C at UC Davis Spring 2014 Who Are We? 10 50
  • 10.
    Slides by JonathanEisen for BIS2C at UC Davis Spring 2016 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
  • 11.
    Slides by JonathanEisen for BIS2C at UC Davis Spring 2016 Clicker 12
  • 12.
    Slides by JonathanEisen for BIS2C at UC Davis Spring 2016 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
  • 13.
    Slides by JonathanEisen for BIS2C at UC Davis Spring 2016 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
  • 14.
    Slides by JonathanEisen for BIS2C at UC Davis Spring 2014 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
  • 15.
    Slides by JonathanEisen for BIS2C at UC Davis Spring 2014 Classes of symbiosis Organism Class of symbiosis A B Mutualism + + Commensalism + 0 Parasitism + - 16 Why All The Attention for Commensalism?
  • 16.
    Slides by JonathanEisen for BIS2C at UC Davis Spring 2014 Classes of symbiosis Organism Class of symbiosis A B Mutualism + + Commensalism + 0 Parasitism + - 17 Is this Mutualism?
  • 17.
    Slides by JonathanEisen for BIS2C at UC Davis Spring 2014 Classes of symbiosis Organism Class of symbiosis A B Mutualism + + Commensalism + 0 Parasitism + - 18 Is this Parasitism?
  • 18.
    Slides by JonathanEisen for BIS2C at UC Davis Spring 2014 Classes of symbiosis Organism Class of symbiosis A B Mutualism + + Commensalism + 0 Parasitism + - 19 Some of Each
  • 19.
    Slides by JonathanEisen for BIS2C at UC Davis Spring 2016 Why Now? Studies Like This … 20 Turnbaugh et al Nature. 2006 444(7122):1027-31.
  • 20.
    Slides by JonathanEisen for BIS2C at UC Davis Spring 2014 Microbiome Involved in Many Functions • Digestion • Vitamin Production • Protection from parasites / pathogens • Metabolic rate • Immune regulation • Odor • Behavior 21
  • 21.
    Slides by JonathanEisen for BIS2C at UC Davis Spring 2016 22 Why Now II: DNA Sequencing Advances
  • 22.
    Slides by JonathanEisen for BIS2C at UC Davis Spring 2016 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
  • 23.
    Slides by JonathanEisen for BIS2C at UC Davis Spring 2016 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
  • 24.
    Slides by JonathanEisen for BIS2C at UC Davis Spring 2014 25 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
  • 25.
    Slides by JonathanEisen for BIS2C at UC Davis Spring 2014 26 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
  • 26.
    Slides by JonathanEisen for BIS2C at UC Davis Spring 2016 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
  • 27.
    Slides by JonathanEisen for BIS2C at UC Davis Spring 2014 Clicker 28
  • 28.
    Slides by JonathanEisen for BIS2C at UC Davis Spring 2014 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
  • 29.
    Slides by JonathanEisen for BIS2C at UC Davis Spring 2014 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. 30
  • 30.
    Slides by JonathanEisen for BIS2C at UC Davis Spring 2014 How could you tell if one of the rRNA genes you sequence came from a mitochondrion? 31
  • 31.
    Slides by JonathanEisen for BIS2C at UC Davis Spring 2014 How could you tell if one of the rRNA genes you sequence came from a fungus? 32
  • 32.
    Slides by JonathanEisen for BIS2C at UC Davis Spring 2016 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 33
  • 33.
    Slides by JonathanEisen for BIS2C at UC Davis Spring 2014 The Human Microbiome 34
  • 34.
  • 35.
    Slides by JonathanEisen for BIS2C at UC Davis Spring 2016 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 36
  • 36.
    Slides by JonathanEisen for BIS2C at UC Davis Spring 2014 37
  • 37.
    Slides by JonathanEisen for BIS2C at UC Davis Spring 2014 38
  • 38.
    Slides by JonathanEisen for BIS2C at UC Davis Spring 2014 39
  • 39.
    Slides by JonathanEisen for BIS2C at UC Davis Spring 2014 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
  • 40.
    Slides by JonathanEisen for BIS2C at UC Davis Spring 2014 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
  • 41.
    Slides by JonathanEisen for BIS2C at UC Davis Spring 2014 Variability Across People 42Huttenhower et al. 2012.
  • 42.
    Slides by JonathanEisen for BIS2C at UC Davis Spring 2016 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 43
  • 43.
    Slides by JonathanEisen for BIS2C at UC Davis Spring 2014 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
  • 44.
    !45 Morgan et al.Genome Biology 2012 13:R79 doi:10.1186/gb-2012-13-9-r79
  • 45.
    !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
  • 46.
    Slides by JonathanEisen for BIS2C at UC Davis Spring 2014 Microbiome Involved in Many Functions • Digestion • Vitamin Production • Protection from parasites / pathogens • Metabolic rate • Immune regulation • Odor • Behavior 47
  • 47.
    Slides by JonathanEisen for BIS2C at UC Davis Spring 2016 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 48
  • 48.
    Slides by JonathanEisen for BIS2C at UC Davis Spring 2014 Infant Microbiome, Birth, and Milk 49 David Mills
  • 49.
    Slides by JonathanEisen for BIS2C at UC Davis Spring 2014 Other Sources 50
  • 50.
    Slides by JonathanEisen for BIS2C at UC Davis Spring 2014 Disturbing the Microbiome 51 Antibiotics Diet Changes Hygiene Hypothesis C-sections
  • 51.
    Slides by JonathanEisen for BIS2C at UC Davis Spring 2014 C-Sections Alter “Normal” Colonization 52 Maria Gloria Dominguez-Bello
  • 52.
    Slides by JonathanEisen for BIS2C at UC Davis Spring 2016 Diet Changes Alter Microbiome 53 Switch to solid foods
  • 53.
    Slides by JonathanEisen for BIS2C at UC Davis Spring 2014 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 Phylotyperelativeabundance(%) Subject 6 0 20 40 60 80 100 Phylotyperelativeabundance(%) L. iners Atopobium Sneathia Corynebacterium Gemella Finegoldia Prevotella Peptostreptococcus Peptoniphilus Anaerococcus Streptococcus Parvimonas Staphylococcus Subject 12 0 20 40 60 80 100 Phylotyperelativeabundance(%) 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
  • 54.
    Slides by JonathanEisen for BIS2C at UC Davis Spring 2014 Hygiene Hypothesis 55 Susan Lynch Dogs, Dust, Microbiomes and Asthma
  • 55.
    Slides by JonathanEisen for BIS2C at UC Davis Spring 2016 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 56
  • 56.
    Slides by JonathanEisen for BIS2C at UC Davis Spring 2014 Microbiome Transplant 57
  • 57.
    Slides by JonathanEisen for BIS2C at UC Davis Spring 2014 Restoring the Microbiome: Probiotics and Prebiotics 58
  • 58.
    Slides by JonathanEisen for BIS2C at UC Davis Spring 2014 Intestinal Transplant 59 Hartman et al. PNAS 2009
  • 59.
    Slides by JonathanEisen for BIS2C at UC Davis Spring 2014 Coprophagia 60
  • 60.
    Slides by JonathanEisen for BIS2C at UC Davis Spring 2014 Transfaunation 61
  • 61.
    Slides by JonathanEisen for BIS2C at UC Davis Spring 2014 Fecal “transplants” 62
  • 62.
    Slides by JonathanEisen for BIS2C at UC Davis Spring 2014 Openbiome 63
  • 63.
    Slides by JonathanEisen for BIS2C at UC Davis Spring 2014 DIY Fecal Transplant 64
  • 64.
    Slides by JonathanEisen for BIS2C at UC Davis Spring 2014 65 DIY Fecal Transplant
  • 65.
    Slides by JonathanEisen for BIS2C at UC Davis Spring 2014 66
  • 66.
    Slides by JonathanEisen for BIS2C at UC Davis Spring 2014 66
  • 67.
    Slides by JonathanEisen for BIS2C at UC Davis Spring 2016 Get Involved 67 Kitty Microbiome