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The Era of the Microbiome - Talk by Jonathan Eisen
1. !
DNA based Studies of Microbial Diversity
!
Jonathan A. Eisen
!
University of California, Davis
!
!1
!
!
The Era of the Microbiome
!
Jonathan A. Eisen
University of California, Davis
!
December 6, 2013
!
Cleveland Clinic 11th Annual Dr. Roizen's
Preventive and Integrative Medicine Conference
!
6. Pubmed Hits for “Microbiome” vs. “Elvis”
1400
1050
700
350
0
2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012
Microbiome Elvis
7. The Microbiome
“The Nobel laureate Joshua Lederberg has
suggested using the term "microbiome" to
describe the collective genome of our
indigenous microbes (microflora), the idea being
that a comprehensive genetic view of Homo
sapiens as a life-form should include the genes
in our microbiome”
Lora Hooper and Jeff Gordon (Commensal Host-Bacterial Relationships in
the Gut Science 11 May 2001: Vol. 292. no. 5519, pp. 1115 - 1118
8. 1400
1050
700
350
0
The Rise of the Microbiome
Pubmed “Microbiome” Hits
00 01 02 03 04 05 06 07 08 09 10 11 12
16. Microbial Diversity
• Microscope picture
!16
• Microbes are small
• But diversity and numbers are
very high
• Appearance not a good
indicator of type or function
• Field observations of limited
value
36. !36
DNA
extraction
PCR
PCR Sequence
rRNA genes
Phylogenetic tree Sequence alignment = Data matrix
rRNA1
Yeast
Makes lots of
copies of the
rRNA genes in
sample
E. coli
Humans
A
T
A
T
C
A
G
A
A
C
A
T
C
A
C
A
A
G
A
G
C
T
G
T
rRNA1
Yeast
E. coli Humans
rRNA1
5’ ...TACAGTATAGGTGG
AGCTAGCGATCGATCG
A... 3’
rRNA Gene PCR
37. !37
DNA
extraction
rRNA Gene PCR
PCR
PCR Sequence
rRNA genes
Phylogenetic tree Sequence alignment = Data matrix
rRNA1
Yeast
Makes lots of
copies of the
rRNA genes in
sample
E. coli
Humans
A
T
A
T
C
A
G
A
A
C
A
T
C
A
C
A
A
G
A
G
C
T
G
T
rRNA1
Yeast
E. coli Humans
rRNA1
5’ ...TACAGTATAGGTGG
AGCTAGCGATCGATCG
A... 3’
PRIMERS
38. !38
DNA
extraction
rRNA Gene PCR
PCR
PCR Sequence
rRNA genes
Phylogenetic tree Sequence alignment = Data matrix
rRNA1
rRNA2
Makes lots of
copies of the
rRNA genes in
sample
rRNA1
5’ ...ACACACATAGGTG
GAGCTAGCGATCGATC
GA... 3’
E. coli
Humans
A
T
A
T
C
A
G
A
A
C
A
T
C
A
C
A
A
G
A
G
C
T
G
T
rRNA1
rRNA2
E. coli Humans
rRNA2
5’ ...TACAGTATAGGTGG
AGCTAGCGATCGATCG
A... 3’
Yeast Yeast T A C A G T
39. !39
DNA
extraction
PCR
PCR Sequence
rRNA genes
Phylogenetic tree Sequence alignment = Data matrix
rRNA2 rRNA2
rRNA1
rRNA2
Makes lots of
copies of the
rRNA genes in
sample
rRNA1
5’...ACACACATAGGTGGAGCTAGC
GATCGATCGA... 3’
E. coli
Humans
A
T
A
T
C
A
G
A
A
C
A
T
C
A
C
A
A
G
A
G
C
T
G
T
rRNA1
rRNA3 rRNA4
E. coli Humans
5’..TACAGTATAGGTGGAGCTAGC
GACGATCGA... 3’
rRNA3
5’...ACGGCAAAATAGGTGGATTCT
AGCGATATAGA... 3’
rRNA4
5’...ACGGCCCGATAGGTGGATTCT
AGCGCCATAGA... 3’
rRNA3 C A C T G T
rRNA4 C A C A G T
Yeast T A C A G T
Yeast
rRNA Gene PCR
45. !45
DNA
extraction
PCR Sequence
all genes
Phylotyping
Phylogenetic tree
Shotgun
rRNA1
rRNA2
rRNA3 rRNA4
E. coli Humans
Yeast
Shotgun Metagenomics
46. !46
DNA
extraction
Shotgun Metagenomics
PCR Sequence
all genes
Phylogenetic tree
Shotgun
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
articles
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
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.
47. Metagenomics
articles
Community structure and metabolism
through reconstruction of microbial
genomes from the environment
Gene W. Tyson1, Jarrod Chapman3,4, Philip Hugenholtz1, Eric E. Allen1, Rachna J. Ram1, Paul M. Richardson4, Victor V. Solovyev4,
Edward M. Rubin4, Daniel S. Rokhsar3,4 & Jillian F. Banfield1,2
1Department of Environmental Science, Policy and Management, 2Department of Earth and Planetary Sciences, and 3Department of Physics, University of California,
Berkeley, California 94720, USA
4Joint Genome Institute, Walnut Creek, California 94598, USA
photosynthetic biomass Surface water were collected aboard from three sites off February 2003. Additional aboard the SV S” in May are indicated on Fig. S1; sampling protocols one expedition to was extracted from genomic libraries with 2 to 6 kb were made prepared plasmid RESEARCH ...........................................................................................................................................................................................................................
Microbial communities are vital in the functioning of all ecosystems; however, most microorganisms are uncultivated, and their
roles in natural systems are unclear. Here, using random shotgun sequencing of DNA from a natural acidophilic biofilm, we report
reconstruction of near-complete genomes of Leptospirillum group II and Ferroplasma type II, and partial recovery of three other
genomes. This was possible because the biofilm was dominated by a small number of species populations and the frequency of
genomic rearrangements and gene insertions or deletions was relatively low. Because each sequence read came from a different
individual, we could determine that single-nucleotide polymorphisms are the predominant form of heterogeneity at the strain level.
The Leptospirillum group II genome had remarkably few nucleotide polymorphisms, despite the existence of low-abundance
variants. The Ferroplasma type II genome seems to be a composite from three ancestral strains that have undergone homologous
recombination to form a large population of mosaic genomes. Analysis of the gene complement for each organism revealed the
pathways for carbon and nitrogen fixation and energy generation, and provided insights into survival strategies in an extreme
environment.
The study of microbial evolution and ecology has been revolutio-nized
by DNA sequencing and analysis1–3. However, isolates have
been the main source of sequence data, and only a small fraction of
microorganisms have been cultivated4–6. Consequently, focus has
shifted towards the analysis of uncultivated microorganisms via
cloning of conserved genes5 and genome fragments directly from
the environment7–9. To date, only a small fraction of genes have been
recovered from individual environments, limiting the analysis of
fluorescence in situ hybridization (FISH) revealed that all biofilms
contained mixtures of bacteria (Leptospirillum, Sulfobacillus and, in
a few cases, Acidimicrobium) and archaea (Ferroplasma and other
members of the Thermoplasmatales). The genome of one of these
archaea, Ferroplasma acidarmanus fer1, isolated from the Richmond
mine, has been sequenced previously (http://www.jgi.doe.gov/JGI_
microbial/html/ferroplasma/ferro_homepage.html).
A pink biofilm (Fig. 1a) typical of AMD communities was
!47
Environmental Genome Shotgun
Sequencing of the Sargasso Sea
J. Craig Venter,1* Karin Remington,1 John F. Heidelberg,3
Aaron L. Halpern,2 Doug Rusch,2 Jonathan A. Eisen,3
Dongying Wu,3 Ian Paulsen,3 Karen E. Nelson,3 William Nelson,3
Derrick E. Fouts,3 Samuel Levy,2 Anthony H. Knap,6
Michael W. Lomas,6 Ken Nealson,5 Owen White,3
Jeremy Peterson,3 Jeff Hoffman,1 Rachel Parsons,6
Holly Baden-Tillson,1 Cynthia Pfannkoch,1 Yu-Hui Rogers,4
Hamilton O. Smith1
that ARTICLE
53. Drosophila microbiome
Both natural surveys and laboratory experiments indicate that
host diet plays a major role in shaping the Drosophila bacterial
microbiome.!
!
Laboratory strains provide only a limited model of natural host–
microbe interactions!
62. ARTICLES
A human gut microbial gene catalogue
established by metagenomic sequencing
Junjie Qin1*, Ruiqiang Li1*, Jeroen Raes2,3, Manimozhiyan Arumugam2, Kristoffer Solvsten Burgdorf4,
Chaysavanh Manichanh5, Trine Nielsen4, Nicolas Pons6, Florence Levenez6, Takuji Yamada2, Daniel R. Mende2,
Junhua Li1,7, Junming Xu1, Shaochuan Li1, Dongfang Li1,8, Jianjun Cao1, Bo Wang1, Huiqing Liang1, Huisong Zheng1,
Yinlong Xie1,7, Julien Tap6, Patricia Lepage6, Marcelo Bertalan9, Jean-Michel Batto6, Torben Hansen4, Denis Le
Paslier10, Allan Linneberg11, H. Bjørn Nielsen9, Eric Pelletier10, Pierre Renault6, Thomas Sicheritz-Ponten9,
Keith Turner12, Hongmei Zhu1, Chang Yu1, Shengting Li1, Min Jian1, Yan Zhou1, Yingrui Li1, Xiuqing Zhang1,
Songgang Li1, Nan Qin1, Huanming Yang1, Jian Wang1, Søren Brunak9, Joel Dore´6, Francisco Guarner5,
Karsten Kristiansen13, Oluf Pedersen4,14, Julian Parkhill12, Jean Weissenbach10, MetaHIT Consortium{, Peer Bork2,
S. Dusko Ehrlich6 & Jun Wang1,13
To understand the impact of gut microbes on human health and well-being it is crucial to assess their genetic potential. Here
we describe the Illumina-based metagenomic sequencing, assembly and characterization of 3.3 million non-redundant
microbial genes, derived from 576.7 gigabases of sequence, from faecal samples of 124 European individuals. The gene set,
,150 times larger than the human gene complement, contains an overwhelming majority of the prevalent (more frequent)
microbial genes of the cohort and probably includes a large proportion of the prevalent human intestinal microbial genes. The
genes are largely shared among individuals of the cohort. Over 99% of the genes are bacterial, indicating that the entire
cohort harbours between 1,000 and 1,150 prevalent bacterial species and each individual at least 160 such species, which are
also largely shared. We define and describe the minimal gut metagenome and the minimal gut bacterial genome in terms of
functions present in all individuals and most bacteria, respectively.
Japan8,16,17. !62
Human biogeography
63. !63
!
!
Ecology of the Microbiome 2:
!
Population Biology and Variability
66. Variation in the Vaginal Microbiome
!66
Ravel et al. 2011. PNAS 108(Suppl 1): 4680–4687R
67. !67
Morgan et al. Genome Biology 2012 13:R79 doi:10.1186/gb-2012-13-9-r79
68. !68
Age Diet Location
Many disease states
Pregnant? Exposure
Breast fed? Obese
Morgan et al. Genome Biology 2012 13:R79 doi:10.1186/gb-2012-13-9-r79
69. Variability in Health vs. Disease
ARTICLES PC2
•
•
•
!69
Almost all (99.96%) of the phylogenetically assigned genes belonged
40
30
20
10
0
were within this This suggests that (Supplementary functions important We found two required in all bacteria Cluster (%)
1 Figure 5 | Clusters were ranked by the length and copy number clusters with the groups of 100 clusters. that contains 86% •
•
•
• •
• •
•
•
•
•
•
•
•
• •
•
•
•
•
•
•
•
• •
•
•
•
•
•
•
•
•
•
•
•
Healthy
Crohn’s disease
Ulcerative colitis
P value: 0.031
PC1
Figure 4 | Bacterial species abundance differentiates IBD patients and
healthy individuals. Principal component analysis with health status as
instrumental variables, based on the abundance of 155 species with $1%
genome coverage by the Illumina reads in at least 1 individual of the cohort,
was carried out with 14 healthy individuals and 25 IBD patients (21 ulcerative
colitis and 4 Crohn’s disease) fromSpain (Supplementary Table 1). Two first
components (PC1 and PC2) were plotted and represented 7.3% of whole
inertia. Individuals (represented by points) were clustered and centre of
gravity computed for each class; P-value of the link between health status and
species abundance was assessed using a Monte-Carlo test (999 replicates).
70. • Microbial community different in many disease states
compared to healthy individuals
• Unclear if this is cause or effect in most cases
!70
76. Microbes from the Built Environment
Bacteria of Public Restrooms
Figure 3. Cartoon illustrations of the relative abundance of discriminating taxa on public restroom surfaces. Light blue indicates low
abundance while dark blue indicates high abundance of taxa. (A) Although skin-associated taxa (Propionibacteriaceae, Corynebacteriaceae,
Staphylococcaceae and Streptococcaceae) were abundant on all surfaces, they were relatively more abundant on surfaces routinely touched with
hands. (B) Gut-associated taxa (Clostridiales, Clostridiales group XI, Ruminococcaceae, Lachnospiraceae, Prevotellaceae and Bacteroidaceae) were most
abundant on toilet surfaces. (C) Although soil-associated taxa (Rhodobacteraceae, Rhizobiales, Microbacteriaceae and Nocardioidaceae) were in low
abundance on all restroom surfaces, they were relatively more abundant on the floor of the restrooms we surveyed. Figure not drawn to scale.
doi:10.1371/journal.pone.0028132.g003
!76
The ISME Journal (2012), 1–11
& 2012 International Society for Microbial Ecology All rights reserved 1751-7362/12
www.nature.com/ismej
ORIGINAL ARTICLE
Architectural design influences the diversity and
structure of the built environment microbiome
Steven W Kembel1, Evan Jones1, Jeff Kline1,2, Dale Northcutt1,2, Jason Stenson1,2,
Ann M Womack1, Brendan JM Bohannan1, G Z Brown1,2 and Jessica L Green1,3
1Biology and the Built Environment Center, Institute of Ecology and Evolution, Department of
Biology, University of Oregon, Eugene, OR, USA; 2Energy Studies in Buildings Laboratory,
Department of Architecture, University of Oregon, Eugene, OR, USA and 3Santa Fe Institute,
Santa Fe, NM, USA
Buildings are complex ecosystems that house trillions of microorganisms interacting with each
other, with humans and with their environment. Understanding the ecological and evolutionary
processes that determine the diversity and composition of the built environment microbiome—the
community of microorganisms that live indoors—is important for understanding the relationship
between building design, biodiversity and human health. In this study, we used high-throughput
sequencing of the bacterial 16S rRNA gene to quantify relationships between building attributes and
airborne bacterial communities at a health-care facility. We quantified airborne bacterial community
structure and environmental conditions in patient rooms exposed to mechanical or window
ventilation and in outdoor air. The phylogenetic diversity of airborne bacterial communities was
lower indoors than outdoors, and mechanically ventilated rooms contained less diverse microbial
communities than did window-ventilated rooms. Bacterial communities in indoor environments
contained many taxa that are absent or rare outdoors, including taxa closely related to potential
human pathogens. Building attributes, specifically the source of ventilation air, airflow rates, relative
humidity and temperature, were correlated with the diversity and composition of indoor bacterial
communities. The relative abundance of bacteria closely related to human pathogens was higher
indoors than outdoors, and higher in rooms with lower airflow rates and lower relative humidity.
The observed relationship between building design and airborne bacterial diversity suggests that
we can manage indoor environments, altering through building design and operation the community
of microbial species that potentially colonize the human microbiome during our time indoors.
The ISME Journal advance online publication, 26 January 2012; doi:10.1038/ismej.2011.211
Subject Category: microbial population and community ecology
Keywords: aeromicrobiology; bacteria; built environment microbiome; community ecology; dispersal;
environmental filtering
Microbial Biogeography of Public Restroom Surfaces
Gilberto E. Flores1, Scott T. Bates1, Dan Knights2, Christian L. Lauber1, Jesse Stombaugh3, Rob Knight3,4,
Noah Fierer1,5*
1 Cooperative Institute for Research in Environmental Science, University of Colorado, Boulder, Colorado, United States of America, 2 Department of Computer Science,
University of Colorado, Boulder, Colorado, United States of America, 3 Department of Chemistry and Biochemistry, University of Colorado, Boulder, Colorado, United
States of America, 4 Howard Hughes Medical Institute, University of Colorado, Boulder, Colorado, United States of America, 5 Department of Ecology and Evolutionary
Biology, University of Colorado, Boulder, Colorado, United States of America
Abstract
We spend the majority of our lives indoors where we are constantly exposed to bacteria residing on surfaces. However, the
diversity of these surface-associated communities is largely unknown. We explored the biogeographical patterns exhibited
by bacteria across ten surfaces within each of twelve public restrooms. Using high-throughput barcoded pyrosequencing of
the 16 S rRNA gene, we identified 19 bacterial phyla across all surfaces. Most sequences belonged to four phyla:
Actinobacteria, Bacteriodetes, Firmicutes and Proteobacteria. The communities clustered into three general categories: those
found on surfaces associated with toilets, those on the restroom floor, and those found on surfaces routinely touched with
hands. On toilet surfaces, gut-associated taxa were more prevalent, suggesting fecal contamination of these surfaces. Floor
surfaces were the most diverse of all communities and contained several taxa commonly found in soils. Skin-associated
bacteria, especially the Propionibacteriaceae, dominated surfaces routinely touched with our hands. Certain taxa were more
common in female than in male restrooms as vagina-associated Lactobacillaceae were widely distributed in female
restrooms, likely from urine contamination. Use of the SourceTracker algorithm confirmed many of our taxonomic
observations as human skin was the primary source of bacteria on restroom surfaces. Overall, these results demonstrate that
restroom surfaces host relatively diverse microbial communities dominated by human-associated bacteria with clear
linkages between communities on or in different body sites and those communities found on restroom surfaces. More
generally, this work is relevant to the public health field as we show that human-associated microbes are commonly found
on restroom surfaces suggesting that bacterial pathogens could readily be transmitted between individuals by the touching
of surfaces. Furthermore, we demonstrate that we can use high-throughput analyses of bacterial communities to determine
sources of bacteria on indoor surfaces, an approach which could be used to track pathogen transmission and test the
efficacy of hygiene practices.
Citation: Flores GE, Bates ST, Knights D, Lauber CL, Stombaugh J, et al. (2011) Microbial Biogeography of Public Restroom Surfaces. PLoS ONE 6(11): e28132.
doi:10.1371/journal.pone.0028132
Editor: Mark R. Liles, Auburn University, United States of America
Received September 12, 2011; Accepted November 1, 2011; Published November 23, 2011
Copyright: ! 2011 Flores et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits
unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funding: This work was supported with funding from the Alfred P. Sloan Foundation and their Indoor Environment program, and in part by the National
Institutes of Health and the Howard Hughes Medical Institute. The funders had no role in study design, data collection and analysis, decision to publish, or
preparation of the manuscript.
Competing Interests: The authors have declared that no competing interests exist.
* E-mail: noah.fierer@colorado.edu
Introduction
More than ever, individuals across the globe spend a large
portion of their lives indoors, yet relatively little is known about the
microbial diversity of indoor environments. Of the studies that
have examined microorganisms associated with indoor environ-ments,
most have relied upon cultivation-based techniques to
detect organisms residing on a variety of household surfaces [1–5].
Not surprisingly, these studies have identified surfaces in kitchens
and restrooms as being hot spots of bacterial contamination.
Because several pathogenic bacteria are known to survive on
surfaces for extended periods of time [6–8], these studies are of
obvious importance in preventing the spread of human disease.
However, it is now widely recognized that the majority of
microorganisms cannot be readily cultivated [9] and thus, the
communities and revealed a greater diversity of bacteria on
indoor surfaces than captured using cultivation-based techniques
[10–13]. Most of the organisms identified in these studies are
related to human commensals suggesting that the organisms are
not actively growing on the surfaces but rather were deposited
directly (i.e. touching) or indirectly (e.g. shedding of skin cells) by
humans. Despite these efforts, we still have an incomplete
understanding of bacterial communities associated with indoor
environments because limitations of traditional 16 S rRNA gene
cloning and sequencing techniques have made replicate sampling
and in-depth characterizations of the communities prohibitive.
With the advent of high-throughput sequencing techniques, we
can now investigate indoor microbial communities at an
unprecedented depth and begin to understand the relationship
between humans, microbes and the built environment.
the stall in), they were likely dispersed manually after women used
the toilet. Coupling these observations with those of the
distribution of gut-associated bacteria indicate that routine use of
toilets results in the dispersal of urine- and fecal-associated bacteria
throughout the restroom. While these results are not unexpected,
they do highlight the importance of hand-hygiene when using
public restrooms since these surfaces could also be potential
vehicles for the transmission of human pathogens. Unfortunately,
previous studies have documented that college students (who are
likely the most frequent users of the studied restrooms) are not
always the most diligent of hand-washers [42,43].
Results of SourceTracker analysis support the taxonomic
patterns highlighted above, indicating that human skin was the
primary source of bacteria on all public restroom surfaces
examined, while the human gut was an important source on or
around the toilet, and urine was an important source in women’s
restrooms (Figure 4, Table S4). Contrary to expectations (see
above), soil was not identified by the SourceTracker algorithm as
being a major source of bacteria on any of the surfaces, including
floors (Figure 4). Although the floor samples contained family-level
taxa that are common in soil, the SourceTracker algorithm
probably underestimates the relative importance of sources, like
time, the
begun to take
of outside
from plants
hours after
were shut
proportion of
the human
back to pre-vious
which
26 Janu-ary
Journal,
mechanically
had lower
diversity than ones with open win-dows.
availability of fresh air translated
proportions of microbes associ-ated
human body, and consequently,
pathogens. Although this
that having natural airfl ow
Green says answering that
clinical data; she’s hoping
Stall in
Stall out
Faucet handles
Toilet seat
Toilet flush handle
they move around. But to quantify those con-tributions,
Peccia’s team has had to develop
new methods to collect airborne bacteria and
extract their DNA, as the microbes are much
less abundant in air than on surfaces.
In one recent study, they used air fi lters
to sample airborne particles and microbes
in a classroom during 4 days during which
in indoor microbial
ecology research, Peccia
thinks that the field has
yet to gel. And the Sloan
Foundation’s Olsiewski
shares some of his con-cern.
“Everybody’s gen-erating
vast amounts of
Sink floor
data,” she says, but looking across data sets
can be diffi cult because groups choose dif-ferent
analytical tools. With Sloan support,
though, a data archive and integrated analyt-ical
tools are in the works.
To foster collaborations between micro-biologists,
architects, and building scientists,
the foundation also sponsored a symposium
100
80
60
40
20
0
Average contribution (%)
Door in
Door out
Soap dispenser
Toi l et floo r
SOURCES
Soil
Water
Mouth
Urine
Gut
Skin
Bathroom biogeography. By
swabbing different surfaces in
public restrooms, researchers
determined that microbes vary in
where they come from depend-ing
on the surface (chart).
February 9, 2012
77. !77
!
!
Ecology of the Microbiome 4:
!
Disturbance
87. Vertebrate Microbiomes
Bacteroidetes (red)
ANALYSIS
Firmicutes (blue)
Worlds within worlds: evolution of
the vertebrate gut microbiota
Ruth E. Ley*‡¶, Catherine A. Lozupone*§¶, Micah Hamady||, Rob Knight§ and
Jeffrey I. Gordon*
Abstract | In this Analysis we use published 16S ribosomal RNA gene sequences to compare
the bacterial assemblages that are associated with humans and other mammals, metazoa
and free-living microbial communities that span a range of environments. The composition
of the vertebrate gut microbiota is influenced by diet, host morphology and phylogeny, in this respect the human gut bacterial community is typical of an omnivorous primate.
However, the vertebrate gut microbiota is different from free-living communities that not associated with animal body habitats. We propose that the recently initiated
international Human Microbiome Project should strive to include a broad representation humans, as well as other mammalian and environmental samples, as comparative analyses
of microbiotas and their microbiomes are a powerful way to explore the evolutionary
history of the biosphere.
Vertebrate gut
Figure 3 | Relative abundance of phyla in samples. Bar graph showing the proportion of sequences from each sample
that could be classified at the phylum level. The colour codes for the dominant Firmicutes and Bacteroidetes phyla are shown.
For a complete description of the colour codes see Supplementary information S2 (figure). ‘Other Nature humans’ Reviews refers | Microbiology
to body
habitats other than the gut; for example, the mouth, ear, skin, vagina and vulva (see Supplementary information S1 (table)).
16S ribosomal RNA sequences (%)
100
80
60
40
20
0
Salt water
Salt-water surface
Termite gut
Other human
Subsurface, anoxic or sediment
Mixed water
Soils or freshwater sediments
Non-saline cultured
Insects or earthworms
Genera that cross the divide. Another way to visualize
family of the gammaproteobacteria class. This fam-ily
ANALYSIS
Nat Rev Microbiol. 2008 October ; 6(10): 776–788. doi:10.1038/nrmicro1978.
!87
89. Human superorganism
• Human-microbe associations are very old
• Microbial genes on a person >> human genes
• Your microbes are coadapted to each other
• Microbes known to manipulate EVERYTHING imaginable
in hosts
!89
93. Overselling the Microbiome
• Changes in gut bacteria protect against
stroke
• Scientists look to mummies for obesity
cure
• Good bacteria in the intestine prevent
diabetes, study suggests.
!93
94. Overselling the Microbiome
• Correlation ≠ Causation
• Complexity is astonishing
! 1000s of taxa
! Each with intraspecific variation
! Viruses, bacteria, archaea,
eukaryotes
• Massive risk for false positive
associations
!94
95. !95
!
!
Lesson 4:
!
Lots of New Things Happening
98. Personal Microbiomes
• How will tests be used?
!98
Personal
Genomes
Personal
Microbiomes
Family history ++ --
Disease risk ++ --
Treatment ++ --
Research ++ ++
Data returned ++ ++
100. Last thoughts
• Microbiome counselors?
• Who owns the microbiome?
• Need 1000s of small studies
• Conservation of the microbiome?
• Openness is critical
!100
101. 1400
1050
700
350
0
The Rise of the Microbiome
2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012