The Human Jungle: Exploring the Microbiome

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This is a keynote lecture I gave at a scientific conference on how to translate discoveries about the genome into medical applications. ( http://jointsummits2011.amia.org/keynote-presentations ) I urged them to think of the human body as a lake, and to think of themselves as ecologists. For more information, visit http://carlzimmer.com

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  • Models of a core microbiome. The circles represent the microbial communities in different individuals and can be thought of as either representing different taxa (species, genera, etc.) or representing different genes. (A) “Substantial core” model. Most individuals share most components of the microbiota. (B) “Minimal core” model. All individuals share a few components, and any individual shares many components with a few other individuals, but very little is shared across all individuals. (C) “No core” model. Nothing is shared by all individuals, and most diversity is unique to a given individual. (D) “Gradient” model. Individuals next to each other on a gradient, for example, age or obesity, share many components, but individuals at opposite ends share little or nothing. (E) “Subpopulation” model. Different subpopulations, for example, those defined by geography or disease, have different cores, but nothing is shared across subpopulations. Scenarios C–E would represent situations in which the strategy of identifying core species for sequencing, then using these as a scaffold for “omics” studies, would be problematic.\n
  • Models of a core microbiome. The circles represent the microbial communities in different individuals and can be thought of as either representing different taxa (species, genera, etc.) or representing different genes. (A) “Substantial core” model. Most individuals share most components of the microbiota. (B) “Minimal core” model. All individuals share a few components, and any individual shares many components with a few other individuals, but very little is shared across all individuals. (C) “No core” model. Nothing is shared by all individuals, and most diversity is unique to a given individual. (D) “Gradient” model. Individuals next to each other on a gradient, for example, age or obesity, share many components, but individuals at opposite ends share little or nothing. (E) “Subpopulation” model. Different subpopulations, for example, those defined by geography or disease, have different cores, but nothing is shared across subpopulations. Scenarios C–E would represent situations in which the strategy of identifying core species for sequencing, then using these as a scaffold for “omics” studies, would be problematic.\n
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  • The Human Jungle: Exploring the Microbiome

    1. The Inner Jungle:The Natural History of the Human Microbiome Carl Zimmer Joint Summits on Translational Science Keynote Lecture San Francisco, CA, March 8, 2011
    2. Linsley PondBranford, Connecticuthttp://www.ct.gov/caes/cwp/view.asp?a=2799&q=381326
    3. G. Evelyn Hutchinson (1903-1991)
    4. http://apod.nasa.gov
    5. Linsley Pond as an energy flow Raymond Lindeman www.cedarcreek.umn.edu/
    6. Real food webs are even more complex than this...
    7. The biodiversity of a little lake:4 species of mammals3 birds20 fish~200 zooplankton~1,000 algae~20,000 species total
    8. Why so many species?http://www.glerl.noaa.gov/pubs/brochures/foodweb/LMfoodweb.pdf
    9. Hutchinson’s Niche From The Art of Ecology, 2011
    10. A complicated space From The Art of Ecology, 2011
    11. Heating of Linsley Pond From The Art of Ecology, 2011
    12. Dissolved substances From The Art of Ecology, 2011
    13. From The Art of Ecology, 2011Time opens new niches
    14. From The Art of Ecology, 2011“The History of a Lake”
    15. Transforming invasions: the alewife
    16. Brooks and Dodson 1965, Science 150:28-35
    17. Erosion andeutrophication leave their markBrugham, Ecology 1979 59:19-36
    18. Brugham, Ecology 1979 59:19-36
    19. Max Delbruck (1906-1981)http://en.wikipedia.org/wiki/ File:Max_Delbruck.jpg
    20. Max Delbruckand Salvador Luria
    21. Cold Spring Harbor Archives http://www.flickr.com/photos/cshlarchives/4276595071/
    22. “Molecular genetics, our latestwonder, has taught us to spellout the connectivity of the treeof life in such palpable detail thatwe may say in plain words, ‘Thisriddle of life has been solved.’The ideas of informationstorage, of the replication of thestored information and of its Max Delbruck,programmed readout have Nobel Lecture, 1969become commonplace and havefiltered down into the popularmagazines and grade schooltextbooks.”
    23. blogs.discovermagazine.com/ loom
    24. It will unlock new insights into our origins and history as a species; and it points to new ways of combating disease. The people of many countries have invested in the Human Genome Projects determination of the sequence, and it is hard to see how that investment could have received better returns.http://www.nature.com/nature/journal/v409/n6822/full/409745a0.html
    25. A flood of data...
    26. ...and impatiencehttp://tech.fortune.cnn.com/2010/04/08/the-decade-of-the-human-genome-where-are-the-fab-four/
    27. The Genomic Hype Cycle http://en.wikipedia.org/wiki/Hype_cycle
    28. Yes, we’re like viruses...
    29. ...but we are also like lakes
    30. “Wee animacules”
    31. Diaper ecology
    32. An undeserved fame
    33. Wang et al, Appl Microbiol Biotechnol (2010) 88:1333–1342
    34. Stalking the Wild MicrobiomeWang et al, Appl Microbiol Biotechnol (2010) 88:1333–1342
    35. 100 trillionmicrobes in your body: moremicrobes than allthe humans who have ever lived sigen.org
    36. Imagine producing an elephant’s worth of microbes
    37. Now multiply times five
    38. Microbial abundance raises the question: how human are we? Human: 10 trillion human cells 20,000 human genesMicrobiota: Microbiota:100 trillion microbial cells 20 million microbial genes 99.9% of our genomes the same, but our microbes...?
    39. The microbiome is like an extra organ Sekirov, I. et al. Physiol. Rev. 90: 859-904 2010; doi:10.1152/physrev.00045.2009 Copyright ©2010 American Physiological Society
    40. The microbiomehelps digest food & metabolize drugsAnnu. Rev. Nutr. 2002. 22:283–307doi: 10.1146/annurev.nutr.22.011602.092259
    41. The microbiomemanages theimmune systemFraune and Bosch 2010Bioessays 32: 571–580
    42. The microbiome kills invading pathogensThe skin bacteriaStaphylococcusepidermis makesδ-toxin and killsS. aureus Cogen et al, PLoS ONE 5(1): e8557. doi:10.1371/journal.pone.0008557
    43. The microbiome heals woundsLeft ear: wound Right ear: woundwithout S. epidermis with S. epidermis Lai 2009 Nature Medicine 15, 1377 - 1382 (2009)
    44. The microbiome: anorgan that works asan ecosystem
    45. Diversity from nose to nose Wos-Oxley et al, The ISME Journal (2010) 4, 839–851
    46. Mouth to mouth: 818 bacterial species lives in three people’smouths, 387 shared by all three. Zaura et al BMC Microbiol (2009) vol. 9 (1) pp. 259
    47. What is the shape of the core microbiome?Hamady M , Knight R Genome Res. 2009;19:1141-1152
    48. Or is it a core of genes, not of species?Hamady M , Knight R Genome Res. 2009;19:1141-1152
    49. Diversity within the core Periphery(not in all people) Core (in all people) Costello et al, Science Vol. 326 no. 5960 pp. 1694-1697
    50. r Hair The body has many niches Hairehead Forehead Foreheadernal ear (L) External nose External noseernal ear (R) External ear (R) External ear (R) el External ear (L) External ear (L)mpit (R) Palm (R) Palm (R)mpit (L) Index finger (R) Index finger (R)ernal nose Palm (L) Palm (L) tril (R) Index finger (L) Index finger (L) tril (L) Forearm (R) Forearm (R)ex finger (R) Forearm (L) Forearm (L)m (R) Nostril (R) Nostril (R)ex finger (L) Nostril (L) Nostril (L)earm (R) EAC (R) Armpit (R)earm (L) EAC (L) Armpit (L)m (L) Armpit (R) Sole of foot (R) k of knee (R) Armpit (L) Sole of foot (L) k of knee (L) Sole of foot (R) Back of knee (R)e of foot (R) Sole of foot (L) Back of knee (L)e of foot (L) Back of knee (R) NavelC (R) Back of knee (L) EAC (R)C (L) Navel EAC (L)ns penis Glans penis Glans penis ia minora Labia minora Labia minora l cavity Oral cavity Oral cavity sal tongue Dorsal tongue Dorsal tongue (Sp) Gut (Sp) Gut (Sp) (Sw) Gut (Sw) Gut (Sw) 0.02 0.05 weighted quantitative symmetric UniFrac (Kulczynski) Costello et al, Science Vol. 326 no. 5960 pp. 1694-1697 Fig. S11
    51. Detailed biogeography of thehuman face
    52. Detailed biogeography of thehuman face
    53. Wang et al, Appl Microbiol Biotechnol (2010) 88:1333–1342
    54. From The Art of Ecology, 2011Time opens new niches
    55. Time opens new nichesA 0.9 0.8UniFrac distance 0.7 0.6 variation within people (day-to-day) variation between people 0.5 (on any given day) 0.4 Oral Gut Skin Nostril Hair EAC cavity HabitatB 0.3eighted UniFrac distance 0.2 variation within people 0.1 (day-to-day) Costello et al, Science Vol. 326 no. 5960 pp. 1694-1697 variation between people
    56. Diversity through co-dependence:the case of the elusive mouth resident, Synergistetes Vartoukian et al Environmental Microbiology (2010) 12(4), 916–928
    57. Top: Synergistetes alone in culture grows extremely slowly Bottom: Parvimonas micra speeds up growth of Synergistetes (streak)Vartoukian et al Environmental Microbiology (2010) 12(4), 916–928
    58. It’s a jungle in there
    59. Four mouth microbes that cannot grow aloneActinomyces Streptococcus naeshindii oralisFusobacterium Porphyromonas nucleatum gigivalis Robinson et al, Microbiol Mol Biol Rev. 2010 Sep;74(3):453-76.
    60. Four mouth microbes that cannot grow alone supports the growth ofActinomyces Streptococcus naeshindii oralis supports the growth ofFusobacterium Porphyromonas nucleatum gigivalis Robinson et al, Microbiol Mol Biol Rev. 2010 Sep;74(3):453-76.
    61. Four mouth microbes that cannot grow alone supports the growth ofActinomyces Streptococcus naeshindii oralis supports the growth of supports the growth ofFusobacterium Porphyromonas nucleatum gigivalis Robinson et al, Microbiol Mol Biol Rev. 2010 Sep;74(3):453-76.
    62. Four mouth microbes that cannot grow alone supports the growth ofActinomyces Streptococcus naeshindii oralis supports the growth of supports the growth of supports the growth ofFusobacterium Porphyromonas nucleatum gigivalis Robinson et al, Microbiol Mol Biol Rev. 2010 Sep;74(3):453-76.
    63. Four mouth microbes that cannot grow alone supports the growth ofActinomyces Streptococcus naeshindii oralis supports the growth of supports the cannot support the growth of growth of supports the growth ofFusobacterium Porphyromonas nucleatum gigivalis Robinson et al, Microbiol Mol Biol Rev. 2010 Sep;74(3):453-76.
    64. Four mouth microbes that cannot grow alone supports the growth ofActinomyces Streptococcus naeshindii oralis supports the growth of supports the cannot support on its cannot support the growth of own, but can speed growth of growth if A. naeshindii is also present supports the growth ofFusobacterium Porphyromonas nucleatum gigivalis Robinson et al, Microbiol Mol Biol Rev. 2010 Sep;74(3):453-76.
    65. The Tangled BankKolenbrander et al 2010 Nature Reviews Microbiology 8:471
    66. “The History of a Lake” From The Art of Ecology, 2011
    67. The History of A Microbiome Reid et al Nat Rev Micro (2011) vol. 9 (1) pp. 27-38
    68. From sterile to lush in a matter of weeks Fierer et al, Research in Microbiology 161 (2010) 635e642
    69. Sampling of the microbiota 20minutes after birth
    70. Koenig et al, PNAS 2010
    71. A baby’s microbiomegrows more diverse Koenig et al, PNAS 2010
    72. A lesson from ecology: diversity is healthy Salmonella invades more successfully if mice are treated with antibiotics, have low-diversity microbiomes (LCM), or are germ-freePhoto- http://flic.kr/p/3vhoNg Stecher and Hardt Current Opinion in Microbiology 2010, 14:1–10
    73. Reid et al Nat Rev Micro (2011) vol. 9 (1) pp. 27-38
    74. Reid et al Nat Rev Micro (2011) vol. 9 (1) pp. 27-38
    75. Reid et al Nat Rev Micro (2011) vol. 9 (1) pp. 27-38
    76. Reid et al Nat Rev Micro (2011) vol. 9 (1) pp. 27-38
    77. Reid et al Nat Rev Micro (2011) vol. 9 (1) pp. 27-38
    78. Two invaders that alter ecosystemsAlewife Helicobacter hepatica
    79. As Helicobacter hepaticus becomes more common inmouse cecae (A), microbiome diversity falls (B)KUEHL ET AL, INFECTION AND IMMUNITY, Oct. 2005, p. 6952–6961
    80. A Manmade Catastrophe (for the Microbiome)
    81. Jernberg et al, Microbiology (2010), 156, 3216–3223
    82. Antonopoulos et al, Infection and Immunity (2009) vol. 77 (6) pp. 2367-2375
    83. Robinson et al, Microbiol Mol Biol Rev. 2010 Sep;74(3):453-76.
    84. Microbes guide the flow of energy
    85. Do My Bacteria Make Me Look Fat?Ley RE, Backhed F, Turnbaugh P, et al. 2005. Proc Natl Acad Sci USA 102: 11070–5.
    86. • Germ-free mice given ob/ob or wild-type gut microbes • Chow consumption and exercise the same for both groups • Both sets of mice had similar starting weight and percentage of body fatTurnbaugh, et al. Nature 2006; 444:1027
    87. Sandoval et al, Science 328, 179 (2010)
    88. Kinross et al. Genome Medicine 2011, 3:14
    89. Becoming Ecosystem EngineersAlexander Khoruts, University of Minnestoa
    90. Khoruts’s dilemma: 61 year old patient--Antibiotics for lung infection led to intestinal C. difficile infection Chronic Diarrhea - 8 months Loose bowel movements every 15 minutes Wore diapers at all times Confined to a wheel chair Lost 27 Kg Antibiotic therapy for C. difficile uneffective Khoruts, et al. J. Clin. Gastroenterol. 44, 354–360 (2010)
    91. Microbiome transplant Khoruts, et al. J. Clin. Gastroenterol. 44, 354–360 (2010)
    92. Patient had first solid bowel movement 2 days after treatmentOn 6 month follow up visit, reported daily stools that were well formed Khoruts, et al. J. Clin. Gastroenterol. 44, 354–360 (2010)
    93. Thanks to Jonathan Eisen, Karen Jansson, Rob Knight,Sarkis Mazmanian, David Post, and David Skelly For more information, visit carlzimmer.com

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