The Human Microbiome 101: talk Jonathan Eisen at #FOGM13

The Human Microbiome 101 Jonathan A. Eisen @phylogenomics University of California, Davis Talk for #FOGM13Friday, March 8, 13

Disclosures • I am an advisor for uBiome.Friday, March 8, 13

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Gratuitous Genomics Plot 1500 1125 750 375 0 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012Friday, March 8, 13

Pubmed Hits for Microbiome 1500 1125 750 375 0 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012Friday, March 8, 13

Pubmed Hits for Microbiome 1500 1125 750 Controls? 375 0 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012Friday, March 8, 13

Pubmed Hits for Microbiome, Elvis 1500 1125 750 375 0 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 Microbiome ElvisFriday, March 8, 13

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 - 1118Friday, March 8, 13

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 - 1118Friday, March 8, 13

The Human Microbiome for DummiesFriday, March 8, 13

The Human Microbiome 101Friday, March 8, 13

The Human Microbiome 101 • We are covered in a cloud of microbesFriday, March 8, 13

The Human Microbiome 101 • We are covered in a cloud of microbes • This “microbiome” likely is involved in many important human phenotypesFriday, March 8, 13

The Human Microbiome 101 • We are covered in a cloud of microbes • This “microbiome” LIKELY is involved in many important human phenotypesFriday, March 8, 13

The Human Microbiome 101 • We are covered in a cloud of microbes • This “microbiome” LIKELY is INVOLVED in many important human phenotypesFriday, March 8, 13

The Human Microbiome 101 Chapter 1: Think Like and EcologistFriday, March 8, 13

The Human Microbiome 101 Chapter 2: Incredible Diversity in the CloudFriday, March 8, 13

Studying MicrobesFriday, March 8, 13

Studying Microbes MicroscopyFriday, March 8, 13

Studying Microbes Culturing MicroscopyFriday, March 8, 13

Studying Microbes Culturing Microscopy Count CountFriday, March 8, 13

Studying Microbes Culturing Microscopy Count <<<< CountFriday, March 8, 13

Studying Microbes Solution? Culturing Microscopy Count <<<< CountFriday, March 8, 13

Studying Microbes Solution? DNA Culturing Microscopy Count <<<< CountFriday, March 8, 13

Studying Microbes Solution? rDNA PCR DNA metagenomics Culturing Microscopy Count <<<< CountFriday, March 8, 13

BiogeographyFriday, March 8, 13

Human biogeography Censored CensoredFriday, March 8, 13

Skin •wFriday, March 8, 13

The Human Microbiome 101 Chapter 3: Variation, Variation, VariationFriday, March 8, 13

Friday, March 8, 13

• Microbial community different in many disease states compared to healthy individuals • Unclear if this is cause or effect in most casesFriday, March 8, 13

Morgan et al. Genome Biology 2012 13:R79 doi:10.1186/gb-2012-13-9-r79Friday, March 8, 13

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-r79Friday, March 8, 13

The Human Microbiome 101 Chapter 4: Don’t Oversell the MicrobiomeFriday, March 8, 13

Overselling the MicrobiomeFriday, March 8, 13

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.Friday, March 8, 13

Overselling the Microbiome • Correlation ≠ Causation • Complexity is astonishing • 1000s of taxa • Each with intraspecific variation • Viruses, bacteria, archaea, eukaryotes • Massive risk for false positive associationsFriday, March 8, 13

Turnbaugh et al Nature. 2006 444(7122):1027-31.Friday, March 8, 13

The Human Microbiome 101 Chapter 5: Ecosystem DynamicsFriday, March 8, 13

Colonization Koenig et al. Proc Natl Acad Sci U S A. 2011 108 Suppl 1:4578-85.Friday, March 8, 13

Milk has Microbes ...Friday, March 8, 13

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 hygieneun to take1 Soil swabbing different surfaces in Biology and the Built Environment Center, Institute of Ecology and Evolution, Department ofof 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 Mouthom 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 Urineours 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 environmentshanically 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 arehad 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 (seertions 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, wehat 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 microbialpital 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

Colonization gone wrong Necrotizing enterocolitis C-sectionsFriday, March 8, 13

Disturbing our microbiomeFriday, March 8, 13

Restoring the Microbiome?Friday, March 8, 13

Restoring the MicrobiomeFriday, March 8, 13

Fecal transplantsFriday, March 8, 13

The Human Microbiome 101 Chapter 6: We May Not Be In ChargeFriday, March 8, 13

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

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 hostsFriday, March 8, 13

The Human Microbiome 101 Chapter 8: What NextFriday, March 8, 13

Quantified SelfFriday, March 8, 13

American GutFriday, March 8, 13

uBiomeFriday, March 8, 13

Personal Microbiomes Personal Personal Genomes Microbiomes Family history ++ -- Disease risk ++ -- Treatment ++ -- Research ++ ++ Data returned ++ ++Friday, March 8, 13

Last thoughts • Microbiome counselors? • Who owns the microbiome? • Need 1000s of small studies • Conservation of the microbiome? • Openness is criticalFriday, March 8, 13

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The Human Microbiome 101: talk Jonathan Eisen at #FOGM13

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