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

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 Pond
Branford, Connecticut
http://www.ct.gov/caes/cwp/view.asp?a=2799&q=381326

4. G. Evelyn Hutchinson
(1903-1991)

6. http://apod.nasa.gov

8. Linsley Pond as an energy flow
Raymond Lindeman
www.cedarcreek.umn.edu/

9. Real food webs are even more complex than this...

10. The biodiversity of a little lake:
4 species of mammals
3 birds
20 fish
~200 zooplankton
~1,000 algae
~20,000 species total

11. Why so many species?
http://www.glerl.noaa.gov/pubs/brochures/foodweb/LMfoodweb.pdf

12. Hutchinson’s Niche From The Art of Ecology, 2011

13. A complicated space From The Art of Ecology, 2011

14. Heating of Linsley Pond From The Art of Ecology, 2011

15. Dissolved substances From The Art of Ecology, 2011

16. From The Art of Ecology, 2011
Time opens new niches

17. From The Art of Ecology, 2011
“The History of a Lake”

18. Transforming invasions: the alewife

20. Brooks and Dodson 1965, Science 150:28-35

22. Erosion and
eutrophication leave
their mark
Brugham, Ecology 1979 59:19-36

23. Brugham, Ecology 1979 59:19-36

25. Max Delbruck
(1906-1981)
http://en.wikipedia.org/wiki/
File:Max_Delbruck.jpg

28. Max Delbruck
and Salvador Luria

30. Cold Spring Harbor Archives http://www.flickr.com/photos/cshlarchives/4276595071/

31. “Molecular genetics, our latest
wonder, has taught us to spell
out the connectivity of the tree
of life in such palpable detail that
we may say in plain words, ‘This
riddle of life has been solved.’
The ideas of information
storage, of the replication of the
stored information and of its Max Delbruck,
programmed readout have Nobel Lecture, 1969
become commonplace and have
filtered down into the popular
magazines and grade school
textbooks.”

32. blogs.discover
magazine.com/
loom

33. 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 Project's
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

34. A flood of data...

35. ...and impatience
http://tech.fortune.cnn.com/2010/04/08/the-decade-of-the-human-genome-where-are-the-fab-four/

36. The Genomic Hype Cycle
http://en.wikipedia.org/wiki/Hype_cycle

37. Yes, we’re like viruses...

38. ...but we are also like lakes

40. “Wee animacules”

42. Diaper ecology

43. An undeserved fame

44. Wang et al, Appl Microbiol Biotechnol (2010) 88:1333–1342

45. Stalking the Wild Microbiome
Wang et al, Appl Microbiol Biotechnol (2010) 88:1333–1342

46. 100 trillion
microbes in your
body: more
microbes than all
the humans who
have ever lived
sigen.org

47. Imagine producing an elephant’s worth of microbes

48. Now multiply times five

49. Microbial abundance raises the
question: how human are we?
Human:
10 trillion human cells
20,000 human genes
Microbiota: Microbiota:
100 trillion microbial cells 20 million microbial genes
99.9% of our genomes the same, but our microbes...?

50. 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

51. The microbiome
helps digest food &
metabolize drugs
Annu. Rev. Nutr. 2002. 22:283–307
doi: 10.1146/annurev.nutr.22.011602.092259

52. The microbiome
manages the
immune system
Fraune and Bosch 2010
Bioessays 32: 571–580

53. The microbiome kills invading pathogens
The skin bacteria
Staphylococcus
epidermis makes
δ-toxin and kills
S. aureus
Cogen et al, PLoS ONE 5(1): e8557. doi:10.1371/journal.pone.0008557

54. The microbiome heals wounds
Left ear: wound Right ear: wound
without S. epidermis with S. epidermis
Lai 2009 Nature Medicine 15, 1377 - 1382 (2009)

55. The microbiome: an
organ that works as
an ecosystem

56. Diversity from nose to nose
Wos-Oxley et al, The ISME Journal (2010) 4, 839–851

57. Mouth to mouth: 818 bacterial species lives in three people’s
mouths, 387 shared by all three.
Zaura et al BMC Microbiol (2009) vol. 9 (1) pp. 259

58. What is the shape of the core microbiome?
Hamady M , Knight R Genome Res. 2009;19:1141-1152

59. Or is it a core of genes, not of species?
Hamady M , Knight R Genome Res. 2009;19:1141-1152

60. Diversity within
the core
Periphery
(not in all people)
Core
(in all people)
Costello et al, Science Vol. 326 no. 5960 pp. 1694-1697

61. r Hair
The body has many niches
Hair
ehead Forehead
Forehead
ernal ear (L) External nose
External nose
ernal 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) Navel
C (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

62. Detailed biogeography of the
human face

63. Detailed biogeography of the
human face

64. Wang et al, Appl Microbiol Biotechnol (2010) 88:1333–1342

65. From The Art of Ecology, 2011
Time opens new niches

66. Time opens new niches
A 0.9
0.8
UniFrac 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
Habitat
B 0.3
eighted 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

67. Diversity through co-dependence:
the case of the elusive mouth resident, Synergistetes
Vartoukian et al Environmental Microbiology (2010) 12(4), 916–928

68. 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

69. It’s a jungle in there

70. Four mouth microbes that cannot grow alone
Actinomyces Streptococcus
naeshindii oralis
Fusobacterium Porphyromonas
nucleatum gigivalis
Robinson et al, Microbiol Mol Biol Rev. 2010 Sep;74(3):453-76.

71. Four mouth microbes that cannot grow alone
supports the growth of
Actinomyces Streptococcus
naeshindii oralis
supports the growth of
Fusobacterium Porphyromonas
nucleatum gigivalis
Robinson et al, Microbiol Mol Biol Rev. 2010 Sep;74(3):453-76.

72. Four mouth microbes that cannot grow alone
supports the growth of
Actinomyces Streptococcus
naeshindii oralis
supports the growth of
supports the
growth of
Fusobacterium Porphyromonas
nucleatum gigivalis
Robinson et al, Microbiol Mol Biol Rev. 2010 Sep;74(3):453-76.

73. Four mouth microbes that cannot grow alone
supports the growth of
Actinomyces Streptococcus
naeshindii oralis
supports the growth of
supports the
growth of
supports the growth of
Fusobacterium Porphyromonas
nucleatum gigivalis
Robinson et al, Microbiol Mol Biol Rev. 2010 Sep;74(3):453-76.

74. Four mouth microbes that cannot grow alone
supports the growth of
Actinomyces Streptococcus
naeshindii oralis
supports the growth of
supports the cannot support the
growth of growth of
supports the growth of
Fusobacterium Porphyromonas
nucleatum gigivalis
Robinson et al, Microbiol Mol Biol Rev. 2010 Sep;74(3):453-76.

75. Four mouth microbes that cannot grow alone
supports the growth of
Actinomyces 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 of
Fusobacterium Porphyromonas
nucleatum gigivalis
Robinson et al, Microbiol Mol Biol Rev. 2010 Sep;74(3):453-76.

76. The Tangled Bank
Kolenbrander et al 2010 Nature Reviews Microbiology 8:471

77. “The History of a Lake” From The Art of Ecology, 2011

78. The History of A Microbiome
Reid et al Nat Rev Micro (2011) vol. 9 (1) pp. 27-38

79. From sterile to lush in a matter of weeks
Fierer et al, Research in Microbiology 161 (2010) 635e642

80. Sampling of the microbiota 20
minutes after birth

81. Koenig et al, PNAS 2010

82. A baby’s microbiome
grows more diverse
Koenig et al, PNAS 2010

83. 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-free
Photo- http://flic.kr/p/3vhoNg Stecher and Hardt Current Opinion in Microbiology 2010, 14:1–10

84. Reid et al Nat Rev Micro (2011) vol. 9 (1) pp. 27-38

85. Reid et al Nat Rev Micro (2011) vol. 9 (1) pp. 27-38

86. Reid et al Nat Rev Micro (2011) vol. 9 (1) pp. 27-38

87. Reid et al Nat Rev Micro (2011) vol. 9 (1) pp. 27-38

88. Reid et al Nat Rev Micro (2011) vol. 9 (1) pp. 27-38

89. Two invaders that alter ecosystems
Alewife
Helicobacter hepatica

90. As Helicobacter hepaticus
becomes more common in
mouse cecae (A), microbiome
diversity falls (B)
KUEHL ET AL, INFECTION AND IMMUNITY, Oct. 2005, p. 6952–6961

91. A Manmade Catastrophe (for the Microbiome)

92. Jernberg et al, Microbiology (2010), 156, 3216–3223

93. Antonopoulos et al, Infection and Immunity (2009) vol. 77 (6) pp. 2367-2375

94. Robinson et al, Microbiol Mol Biol Rev. 2010 Sep;74(3):453-76.

95. Microbes guide the flow of energy

96. Do My Bacteria Make Me Look Fat?
Ley RE, Backhed F, Turnbaugh P, et al. 2005. Proc Natl Acad Sci USA 102: 11070–5.

97. • 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
fat
Turnbaugh, et al. Nature 2006; 444:1027

98. Sandoval et al, Science 328, 179 (2010)

99. Kinross et al. Genome Medicine 2011, 3:14

100. Becoming Ecosystem Engineers
Alexander Khoruts, University of Minnestoa

101. 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)

102. Microbiome transplant
Khoruts, et al. J. Clin. Gastroenterol. 44, 354–360 (2010)

103. Patient had first solid bowel movement 2
days after treatment
On 6 month follow up visit, reported daily
stools that were well formed
Khoruts, et al. J. Clin. Gastroenterol. 44, 354–360 (2010)

106. Thanks to Jonathan Eisen, Karen Jansson, Rob Knight,
Sarkis Mazmanian, David Post, and David Skelly
For more information,
visit carlzimmer.com