This document summarizes a presentation about the human microbiome. It discusses how humans are covered in a cloud of microbes known as the microbiome. This microbiome likely plays an important role in human health and phenotypes. The presentation covers the diversity of microbes in the microbiome and how they vary significantly based on many factors like age, diet, location, and disease states. It also discusses challenges in studying microbes and how DNA sequencing techniques have helped overcome those challenges. The presentation warns against overselling the role of the microbiome in health and emphasizes the complexity of the ecosystem and interactions between the host and microbes. It also discusses how microbes colonize humans and dynamics within the ecosystem.

1. The Human Microbiome 101
Jonathan A. Eisen
@phylogenomics
University of California, Davis
Talk for #FOGM13
Friday, March 8, 13

2. The Human Microbiome 101
Jonathan A. Eisen
@phylogenomics
University of California, Davis
Talk for #FOGM13
Friday, March 8, 13

3. Disclosures
• I am an advisor for uBiome.
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4. 1500
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5. Gratuitous Genomics Plot
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6. Pubmed Hits for Microbiome
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7. Pubmed Hits for Microbiome
1500
1125
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Controls?
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8. Pubmed Hits for Microbiome, Elvis
1500
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Microbiome Elvis
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9. 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
Friday, March 8, 13

10. The Microbiome
• “The Nobel laureate Joshua Lederberg
has suggested using the term
"microbiome" to describe the collective
genome of our indigenous microbes
Badomics Word?
(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
Friday, March 8, 13

11. The Microbiome
• “The Nobel laureate Joshua Lederberg
has suggested using the term
"microbiome" to describe the collective
genome of our indigenous microbes
Badomics Word?
(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
Friday, March 8, 13

12. The Human Microbiome for Dummies
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13. The Human Microbiome 101
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14. The Human Microbiome 101
• We are covered in a cloud of microbes
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15. The Human Microbiome 101
• We are covered in a cloud of microbes
• This “microbiome” likely is involved in
many important human phenotypes
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16. The Human Microbiome 101
• We are covered in a cloud of microbes
• This “microbiome” LIKELY is involved in
many important human phenotypes
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17. The Human Microbiome 101
• We are covered in a cloud of microbes
• This “microbiome” LIKELY is INVOLVED
in many important human phenotypes
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18. The Human Microbiome 101
Chapter 1:
Think Like and Ecologist
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19. The Human Microbiome 101
Chapter 2:
Incredible Diversity in the Cloud
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20. Studying Microbes
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21. Studying Microbes
Microscopy
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22. Studying Microbes
Culturing Microscopy
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23. Studying Microbes
Culturing Microscopy
Count Count
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24. Studying Microbes
Culturing Microscopy
Count <<<< Count
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25. Studying Microbes
Solution?
Culturing Microscopy
Count <<<< Count
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26. Studying Microbes
Solution?
DNA
Culturing Microscopy
Count <<<< Count
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27. Studying Microbes
Solution?
rDNA PCR
DNA
metagenomics
Culturing Microscopy
Count <<<< Count
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28. Studying Microbes
Solution?
rDNA PCR
DNA
metagenomics
Culturing Microscopy
Count <<<< Count
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29. Biogeography
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30. Human biogeography
Censored
Censored
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31. Skin
•w
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32. The Human Microbiome 101
Chapter 3:
Variation, Variation, Variation
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33. Friday, March 8, 13

34. • Microbial community different in many disease
states compared to healthy individuals
• Unclear if this is cause or effect in most cases
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35. Morgan et al. Genome Biology 2012 13:R79 doi:10.1186/gb-2012-13-9-r79
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36. Age Diet Location
Many disease states
Pregant? Exposure
Breast fed? Obese
Morgan et al. Genome Biology 2012 13:R79 doi:10.1186/gb-2012-13-9-r79
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37. The Human Microbiome 101
Chapter 4:
Don’t Oversell the Microbiome
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38. Overselling the Microbiome
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39. 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.
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40. 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
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41. Turnbaugh et al Nature. 2006 444(7122):1027-31.
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42. The Human Microbiome 101
Chapter 5:
Ecosystem Dynamics
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43. Colonization
Koenig et al. Proc Natl Acad Sci U S A. 2011 108 Suppl 1:4578-85.
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44. Milk has Microbes ...
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45. The Built Environment
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
The ISME Journal (2012), 1–11 hands. On toilet surfaces, gut-associated taxa were more prevalent, suggesting fecal contamination of these surfaces. Floor
& 2012 International Society for Microbial Ecology All rights reserved 1751-7362/12
surfaces were the most diverse of all communities and contained several taxa commonly found in soils. Skin-associated
www.nature.com/ismej 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
ORIGINAL ARTICLE 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
Architectural design influences the diversity and 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
structure of the built environment microbiome generally, this work is relevant to the public health field as we show that human-associated microbes arePublic Restrooms
Bacteria of 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
time, theSteven W Kembel1, Evan Jones1, Jeff Kline1,2, Dale Northcutt1,2, Jason Stenson1,2,
100 SOURCES
Ann M Womack1, Brendan JM Bohannan1, G Z Brown1,2 and Jessica L Green1,3 Bathroom biogeography. By practices.
efficacy of hygiene
un to take1
Soil
swabbing different surfaces in
Biology and the Built Environment Center, Institute of Ecology and Evolution, Department of
of outside 80 Water
Average contribution (%)
Biology, University of Oregon, Eugene, OR, USA; 2Energy Studies in Buildings Laboratory, public restrooms, researchers ST, Knights D, Lauber CL, Stombaugh J, et al. (2011) Microbial Biogeography of Public Restroom Surfaces. PLoS ONE 6(11): e28132.
Citation: Flores GE, Bates
doi:10.1371/journal.pone.0028132
Mouth
om plants 3
Department of Architecture, University of Oregon, Eugene, OR, USA and Santa Fe Institute, determined thatEditor: Mark R. Liles, Auburn University, United States of America
microbes vary in
Urine
ours after Fe, NM, USA
Santa 60
Gut
where they come from September 12, 2011; Accepted November 1, 2011; Published November 23, 2011
Received depend-
ere shut Skin ing on the surface (chart). 2011 Flores et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits
Copyright: ß
40 unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
ortion of Buildings are complex ecosystems that house trillions of microorganisms interacting with each Funding: This work was supported with funding from the Alfred P. Sloan Foundation and their Indoor Environment program, and in part by the National
e human other, with humans and with their environment. Understanding the ecological and evolutionarypant in indoor microbial the Howard Hughes Medical Institute. The funders had no role in study design, data collection and analysis, decision to publish, or
Institutes of Health and
processes that determine the diversity and composition of the built environment microbiome—the
20 Figure 3.preparation illustrations of the relative abundance of discriminating taxa on public restroom surfaces. Light blue indicates low
Cartoon of the manuscript.
ck to pre- community of microorganisms that live indoors—is important for understanding the relationship ecology research, dark blue indicates high abundance of taxa. (A) Although skin-associated taxa (Propionibacteriaceae, Corynebacteriaceae,
abundance while Peccia
Competing Interests: The authors have declared that no competing interests exist.
between building design, biodiversity and human health. In this study, we used high-throughputthinks that the field Streptococcaceae) were abundant on all surfaces, they were relatively more abundant on surfaces routinely touched with
Staphylococcaceae and
hands. (B)*Gut-associatedhas (Clostridiales, Clostridiales group XI, Ruminococcaceae, Lachnospiraceae, Prevotellaceae and Bacteroidaceae) were most
taxa
E-mail: noah.fierer@colorado.edu
0
sequencing of the bacterial 16S rRNA gene to quantify relationships between building attributes and
wh i c h abundant on toilet surfaces. (C) Although soil-associated taxa (Rhodobacteraceae, Rhizobiales, Microbacteriaceae and Nocardioidaceae) were in low
airborne bacterial communities at a health-care facility. We quantified airborne bacterial communityyet to gel. And the Sloan
Do in
t
Fa Sta n
So han t
s
ile oile r
hh t
To ndle
Si or
or
ou
u
lus t sea
e
dle
abundance on all restroom surfaces, they were relatively more abundant on the floor of the restrooms we surveyed. Figure not drawn to scale.
i
ll o
ns
lo
flo
or
all
26 Janu- structure and environmental conditions in patient rooms exposed to mechanical or windowFoundation’s Olsiewski
or
tf
a
Do
pe
St
doi:10.1371/journal.pone.0028132.g003
nk
ile
ventilation and in outdoor air. The phylogenetic diversity of airborne bacterial communities was
dis
Introduction communities and revealed a greater diversity of bacteria on
et
T
Journal, lower indoors than outdoors, and mechanically ventilated rooms contained less diverse microbialshares some of his con-
uc
ap
tf
indoor surfaces than captured using cultivation-based techniques
communities than did window-ventilated rooms. Bacterial communities in indoor environments
hanically cern. the stall in), theythan gen-individualsmanuallythe globe spend a large Results of SourceTracker organisms support the taxonomic are
“Everybody’s ever, dispersed across after women used
More were likely [10–13]. Most of the analysis identified in these studies
To
contained many taxa that are absent or rare outdoors, including taxa closely related to potential the toilet. Coupling lives indoors, yet relatively little is knownthe
portion of their these observations with those of about the patterns highlighted above, indicatingsuggesting that the was the
related to human commensals that human skin organisms are
had lower human pathogens. Building attributes, specifically the source of ventilation air, airflow rates, relativeerating vast amounts of indoor environments. Of the studies that
microbial diversity of
distribution of gut-associated bacteria indicate that routine use of primary source of growing onon all public but rather were deposited
not actively bacteria the surfaces restroom surfaces
y than ones with open and temperature, abundance of bacteriathe diversitythosecomposition of indoor says, but looking resultsexamined sets of urine- and fecal-associatedindoor environ- directly (i.e. touching) or indirectlyimportant source skinor by
humidity
win- relative were around. But to quantify andtocon- pathogens was higher
communities. The they move correlated with closely related human data,” she bacterial toilets across the dispersal
have in data microorganisms associated with bacteria examined, while the human gut was an (e.g. shedding of on cells)
indoors than outdoors, and higher in rooms with lower airflow rates and can be difficult because groups themost have While these results are not unexpected,
bility of fresh air translated tributions, Peccia’s team has had to develop lower relative humidity. ments, restroom. relied upon cultivation-based techniques aroundhumans. Despite these efforts, we still have women’s
throughout choose dif- to the toilet, and urine was an important source in an incomplete
n February 9, 2012
The observed relationship between building design and airborne bacterial diversity suggests that they do highlight the importance a variety of household surfaces [1–5].
detect organisms residing on of hand-hygiene when using restrooms (Figure 4, of bacterial Contrary to expectationswith indoor
understanding Table S4). communities associated (see
rtions of microbes associ- indoor environments, altering through building designand operation the communitytools. WithNot surprisingly, these studies have identified be potential above),environments identified limitations of traditional 16 S rRNA gene
we can manage new methods to collect airborne bacteria and ferent analytical Sloan support,
public restrooms since these surfaces could also surfaces in kitchens soil was not because by the SourceTracker algorithm as
of microbial species that potentially colonize the human microbiome during our time indoors. archive and integrated analyt- of human pathogens. Unfortunately,
an body, and consequently, extract their DNA, as the microbes are much though, a data vehicles for restrooms as being hot spots of bacterial contamination.
and the transmission being acloning source of bacteria on any ofhavesurfaces, including
major and sequencing techniques the made replicate sampling
The ISME Journal advance online publication, 26 January 2012; doi:10.1038/ismej.2011.211 previous studies several pathogenic that college students (whosurvive on
Because have documented bacteria are known to are floors (Figure 4). Although the floor samplesthe communities prohibitive.
pathogens. Although this microbial population air than on surfaces. and in-depth characterizations of contained family-level
Subject Category: less abundant in and community ecology ical tools are in the works. the most for extended periods of time [6–8], these are not are taxa that are common in soil, the SourceTracker algorithm
likely surfaces frequent users of the studied restrooms) studies of
Keywords: aeromicrobiology; bacteria; built environment microbiome; community ecology; dispersal; With the advent of high-throughput sequencing techniques, we
hat having natural airflow
environmental filtering
In one recent study, they used air filters To foster collaborations between micro-hand-washers [42,43]. of human disease. canunderestimates the relative importance of sources, like at an
always obvious importance in preventing the spread
the most diligent of probably now investigate indoor microbial communities
Green says answering that to sample airborne particles and microbes biologists, architects, and building scientists, widely recognized that the majority of unprecedented depth and begin to understand the relationship
However, it is now
microorganisms cannot be readily cultivated [9] and thus, the
clinical data; she’s hoping in a classroom during 4 days during which the foundation also sponsored a symposium microorganisms associated with indoor between humans, microbes and the built environment.
overall diversity of
Introduction microbiome—includes human pathogens and com- In order to begin to comprehensively describe the microbial
pital to participate 8, a study students were present and 4 days during on the microbiome of the built environment largely unknown. Recent use of cultiva- diversity of indoor environments, we characterized the bacterial
Friday, March in 13 environments remains

46. Colonization gone wrong
Necrotizing
enterocolitis
C-sections
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47. Disturbing our microbiome
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48. Restoring the Microbiome?
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49. Restoring the Microbiome
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50. Fecal transplants
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51. The Human Microbiome 101
Chapter 6:
We May Not Be In Charge
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52. S Vertebrate Microbiomes
100
Bacteroidetes (red)
80
16S ribosomal RNA sequences (%)
60
40
20
ANALYSIS Firmicutes (blue)
0
r s ts n r e t t
atetured rm en um
a ate nt fac te gu gu
w ul wo im h w
alt dime sur i bra
te
xed e c arth ed er S er Term
Mi alin r e rs Ot
h at rte Worlds within worlds: evolution of
-s so ate r se t -w Ve
onect hw xic
o Sal the vertebrate gut microbiota
N ns
rf res o
I
so , an
il ce
So su rfa Ruth E. Ley*‡¶, Catherine A. Lozupone*§¶, Micah Hamady||, Rob Knight § and
Jeffrey I. Gordon*
Sub Abstract | In this Analysis we use published 16S ribosomal RNA gene sequences to c
the bacterial assemblages that are associated with humans and other mammals, me
Figure 3 | Relative abundance of phyla in samples. Bar graph showing the proportion of sequences from each sample and free-living microbial communities that span a range of environments. The comp
that could be classified at the phylum level. The colour codes for the dominant Firmicutes and Bacteroidetes phyla are shown. of the vertebrate gut microbiota is influenced by diet, host morphology and phylog
Nature
For a complete description of the colour codes see Supplementary information S2 (figure). ‘Other humans’ refers to body Reviews | Microbiology
in this respect the human gut bacterial community is typical of an omnivorous prim
However, the vertebrate gut microbiota is different from free-living communities th
habitats other than the gut; for example, the mouth, ear, skin, vagina and vulva (see Supplementary information S1 (table)). not associated with animal body habitats. We propose that the recently initiated
international Human Microbiome Project should strive to include a broad represen
humans, as well as other mammalian and environmental samples, as comparative an
of microbiotas and their microbiomes are a powerful way to explore the evolutiona
history of the biosphere.
Genera that cross the divide. Another way to visualize
Friday, March 8, 13
family of the gammaproteobacteria class. This fam-
8–11

53. 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
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54. The Human Microbiome 101
Chapter 8:
What Next
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55. Quantified Self
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56. American Gut
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57. uBiome
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58. Personal Microbiomes
Personal Personal
Genomes Microbiomes
Family history ++ --
Disease risk ++ --
Treatment ++ --
Research ++ ++
Data returned ++ ++
Friday, March 8, 13

59. Last thoughts
• Microbiome counselors?
• Who owns the microbiome?
• Need 1000s of small studies
• Conservation of the microbiome?
• Openness is critical
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