Invited Lecture La Jolla Country Day School La Jolla, CA February 8, 2018

1. “Exploring Your Inner Microbiome”
Invited Lecture
La Jolla Country Day School
La Jolla, CA
February 8, 2018
Dr. Larry Smarr
Director, California Institute for Telecommunications and Information Technology
Harry E. Gruber Professor,
Dept. of Computer Science and Engineering
Jacobs School of Engineering, UCSD
http://lsmarr.calit2.net

2. My Voyage of Discovery to Understand the Microbial Universe Inside Us
Started 40 Years Ago

3. Forty Years Ago
I Did Observational Research on Our Neighbor Galaxy

4. There are 100 billion stars in the
Andromeda galaxy…
…and 100 billion galaxies in the
known universe.

5. It’s a microbial world…
…there are 100 million times as many bacteria on Earth
as stars in the universe.
Microbiology is the ultimate Big Data science!

7. The Cost of Sequencing DNA
Has Fallen Over 100,000x in the Last Ten Years
This Has Enabled Sequencing of
Both Human and Microbial Genomes

8. Marine Microbial Ecology Genome Sequencing Project –
Anchor Dataset Launched March 13, 2007
Measuring the Genetic Diversity
of Ocean Microbes
Specify
Ocean Data
Each Sample
~2000
Microbial
Species

10. 2007:
202 samples
21,752 sequences
2017:
27,000 samples
2.2 billion
sequences

11. November 1, 2017

13. June 8, 2012 June 14, 2012
Interest in the Human Microbiome
Has Moved Quickly From Frontier Science to Public Awareness
August 18, 2012June, 2012

14. To Understand Health and Disease
We Must Consider the Human Microbiome
Inclusion of the “Dark Matter” of the Body
Will Radically Alter Medicine
99% of Your
DNA Genes
Are in Microbe Cells
Not Human Cells
Your Body Has
10 Times As Many Microbe Cells
As DNA-Bearing Human Cells

15. Most of Life’s Evolutionary Time
Was in the Microbial World
You
Are
Here
Source: Carl Woese, et al
Tree of Life Derived from 16S rRNA Sequences

16. When We Think About Biological Diversity
We Typically Think of the Wide Range of Animals
But All These Animals Are in One SubPhylum Vertebrata
of the Chordata Phylum
All images from Wikimedia Commons.
Photos are public domain or by Trisha Shears, Richard Bartz, & Matt Clancy

17. Think of These Phyla of Animals When
You Consider the Biodiversity of Microbes Inside You
Phylum
Annelida
Phylum
Echinodermata
Phylum
Cnidaria
Phylum
Mollusca
Phylum
Arthropoda
Phylum
Chordata
Phylum
Porifera
All images from WikiMedia Commons.
Photos are public domain or by Dan Hershman, Michael Linnenbach, Manuae, B_cool, Nick Hobgood

18. Treating the Human Superorganism:
Your Body is an Ecology!
Nature Reviews
Microbiology
v.9, p. 279 (2011)

19. The Human Microbiome
Has Very Different Microbial Ecologies
Slide from Rob Knight, UCSD

20. As Different as
a Coral Reef’s and a Prairie's Microbiome
Slide from Rob Knight, UCSD

21. Human Stool Contains a Vast Amount of Information:
1 Gram Contains ~1 Billion Microbes, Each With >1 Million DNA Bases
1 Teaspoon Stool Has the Information Content of 1 ton of DVDs

22. I Had Saved Over Three Years Of My Stool Samples
When UCSD Hired Rob Knight
Larry’s 40 Stool Samples Over 3.5 Years
to Rob’s lab on April 30, 2015

23. Microbiome Ecology Diversity Immediately Drops After Colon
Cleanse — Followed By Slow Recovery
Source: Smarr, Hyde, McDonald, Sandborn, Knight

24. Large Jump In Microbiome Ecology After Cleanse — Then
“Wanders” for Two Weeks Back to Normal
Source: Smarr, Hyde, McDonald, Sandborn, Knight

25. November 29, 2016 I Had Robotic Surgery
To Remove 8 Inches of Inflamed Colon

26. Larry Smarr’s Sigmoid Colon Resection
UCSD’s Jacobs Medical Center November 29, 2016
Patient Smarr
With
Robot Arms
Inside Him

27. Gut Microbiome Genus-Level Profiles
Daily Samples Before and After Abdominal Surgery
Colonoscopy Surgery
Source: Embriette Hyde, UCSD

28. Colonoscopy
Surgery
Much Larger Drop in Microbiome Ecology Diversity
Following Surgery Than Following Colonoscopy
Source: Embriette Hyde, UCSD

29. Pre-colonoscopy Post-colonoscopy Pre-surgery Post-surgery
Major Shift in Gut Microbiome Ecology
Following Abdominal Surgery With Return to New Equilibrium State
Source: Embriette Hyde, UCSD

30. The Colonoscopy Didn’t Make Me Look Like a New Person —
But the Surgery Did!
Pre-colonoscopy Post-colonoscopy Pre-surgery
Source: Embriette Hyde, UCSD

31. From War to Gardening:
New Therapeutical Tools for Managing the Microbiome
“I would like to lose the language of warfare,”
said Julie Segre, a senior investigator at
the National Human Genome Research Institute.
”It does a disservice to all the bacteria
that have co-evolved with us
and are maintaining the health of our bodies.”
Will Medical Foods Provide New Tools
for Altering Gut Microbiome?

32. Manipulating Your Microbiome Can Work -- Fecal Microbiome Transfer
Is a Rapidly Growing New Treatment for Clostridia Difficile
Dr. Bill Sandborn,
Chief UCSD GI
Dr. Brigid Boland,
UCSD GI
C. diff is the nation’s
most common
hospital-acquired
infection,
affecting 500,000
and killing 30,000
Americans/year
(CDC)
Fecal transplants
are 90% curative.
OpenBiome supplies
to over 500 hospitals
in all 50 states,
so far 10,000
transplants.
www.cidrap.umn.edu/news-perspective/2015/02/cdc-puts-c-difficile-burden-453000-cases-29000-deaths

33. Fecal Transplants
From Healthy Donor
To C. Diff Patients
Source: Knight Lab, UCSD
Mouth
Skin
Vagina
Stool

34. Massive Research is Underway to Discover
A Wide Range of New Techniques for Manipulating Your Microbiome
www.huffingtonpost.com/entry/gut-bacteria-microbiome-disease_us_57068c55e4b053766188f383
www.synlogictx.com

35. The United States Population’s Human Gut Microbiome
Has Diverged a Great Deal from Hunter-Gatherers
“The microbiome of uncontacted Amerindians,” J. C. Clemente, et al. Science Advances 1, e1500183 (2015).
[Amerindians in
Venezuela/Columbia]
[Africa]
U.S. Human
Microbiome
Project
Missing Microbes

36. We Must Move From Combating Single Microbe Diseases to
Developing the Human/Microbiome System Approach to Public Health
Bach (2002) N Engl J Med, Vol. 347, 911-920
2014
For Public Health It is Still About Microbes,
But from Single Species to Entire Ecologies

37. The Coupled Neural, Immune, and Microbiome Systems
Provide a Model Explaining How Nutrition Can Alter Neurodevelopment

38. Gut Microbes Regulate Serotonin Production,
90% of Which is in the Large Intestine
“It's almost unthinkable
that the gut is not playing a critical role in mind states,"
says gastroenterologist Emeran Mayer, MD,
director of the Center for Neurobiology of Stress at UCLA
Cell 161 264-276 (2015)

39. The Microbiome–Gut–Brain Axis
Provides New Systemic Insights into Shifts in Behavior and Disease
Source: Montiel-Castro, et al.
Frontiers in Integrative Neuroscience 2013
Particularly Important for Healthy Aging

40. Many New Research Studies are Demonstrating Deep Relationships
Between the Gut Microbiome and Behavioral Disorders

41. Center for
Microbiome
Innovation
Seminars
Faculty
Hiring
Education
UCSD Microbial Sciences Initiative
Instrument
Cores
Seed Grants
Fellowships
Chancellor Khosla Launched the UC San Diego
Microbiome and Microbial Sciences Initiative October 29, 2015

42. …and over 120 UCSD Faculty

43. Thanks to Our Great Team!
Calit2@UCSD
Future Patient Team
Jerry Sheehan
Tom DeFanti
Joe Keefe
John Graham
Kevin Patrick
Mehrdad Yazdani
Jurgen Schulze
Andrew Prudhomme
Philip Weber
Fred Raab
Ernesto Ramirez
JCVI Team
Karen Nelson
Shibu Yooseph
Manolito Torralba
Ayasdi
Devi Ramanan
Pek Lum
UCSD Metagenomics Team
Weizhong Li
Sitao Wu
SDSC Team
Michael Norman
Mahidhar Tatineni
Robert Sinkovits
UCSD Health Sciences Team
David Brenner
Rob Knight Lab
Justine Debelius
Embriette Hyde
Jose Navas
Gail Ackermann
Greg Humphrey
William J. Sandborn Lab
Elisabeth Evans
John Chang
Brigid Boland
Dell/R Systems
Brian Kucic
John Thompson