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“Deciphering the Dynamic Coupling of 
the Human Immune System and the Gut Microbiome” 
Overview 
Data-Enabled Life Sciences Research (DELSA) 
DELSA Workshop IV 
Bethesda, MD 
May 16, 2013 
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 
1
Why Did I Have an Autoimmune Disease like IBD? 
Despite decades of research, 
the etiology of Crohn's disease 
remains unknown. 
Its pathogenesis may involve 
a complex interplay between 
host genetics, 
immune dysfunction, 
and microbial or environmental factors. 
--The Role of Microbes in Crohn's Disease 
So I Set Out to Quantify All Three! 
Paul B. Eckburg & David A. Relman 
Clin Infect Dis. 44:256-262 (2007)
I Wondered if Crohn’s is an Autoimmune Disease, 
Did I Have a Personal Genomic Polymorphism? 
From www.23andme.com 
SNPs Associated with CD 
Polymorphism in 
Interleukin-23 Receptor Gene 
— 80% Higher Risk 
of Pro-inflammatory 
Immune Response 
NOD2 
ATG16L1 
IRGM 
Now Have My 
Full Human Genome 
Sequenced 
Source: Larry Smarr, Calit2
Fine Time Resolution Sampling Reveals Distinct 
Dynamics of Innate and Adaptive Immune System 
Normal 
Normal
We Find Major Shifts in Microbial Ecology 
Between Healthy and Two Forms of IBD 
Collapse of 
Bacteroidetes 
Explosion of 
Proteobacteria 
Source: Larry Smarr, Calit2
I Can Track Changes in My Microbiome Before and After 
1 Month Antibiotic & 2 Month Prednisone Therapy 
Therapy Greatly Reduced Two Phyla, 
But Massive Reduction in Bacteroidetes 
And Large % Proteobacteria Remain 
Small Changes 
With No Therapy 
Reduced 45x 
Reduced 90x 
I am Trapped in a Local Ecological Equilibrium 
“Far from Healthy” 
Source: Larry Smarr, Calit2

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Deciphering the Dynamic Coupling of the Human Immune System and the Gut Microbiome

  • 1. “Deciphering the Dynamic Coupling of the Human Immune System and the Gut Microbiome” Overview Data-Enabled Life Sciences Research (DELSA) DELSA Workshop IV Bethesda, MD May 16, 2013 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 1
  • 2. Why Did I Have an Autoimmune Disease like IBD? Despite decades of research, the etiology of Crohn's disease remains unknown. Its pathogenesis may involve a complex interplay between host genetics, immune dysfunction, and microbial or environmental factors. --The Role of Microbes in Crohn's Disease So I Set Out to Quantify All Three! Paul B. Eckburg & David A. Relman Clin Infect Dis. 44:256-262 (2007)
  • 3. I Wondered if Crohn’s is an Autoimmune Disease, Did I Have a Personal Genomic Polymorphism? From www.23andme.com SNPs Associated with CD Polymorphism in Interleukin-23 Receptor Gene — 80% Higher Risk of Pro-inflammatory Immune Response NOD2 ATG16L1 IRGM Now Have My Full Human Genome Sequenced Source: Larry Smarr, Calit2
  • 4. Fine Time Resolution Sampling Reveals Distinct Dynamics of Innate and Adaptive Immune System Normal Normal
  • 5. We Find Major Shifts in Microbial Ecology Between Healthy and Two Forms of IBD Collapse of Bacteroidetes Explosion of Proteobacteria Source: Larry Smarr, Calit2
  • 6. I Can Track Changes in My Microbiome Before and After 1 Month Antibiotic & 2 Month Prednisone Therapy Therapy Greatly Reduced Two Phyla, But Massive Reduction in Bacteroidetes And Large % Proteobacteria Remain Small Changes With No Therapy Reduced 45x Reduced 90x I am Trapped in a Local Ecological Equilibrium “Far from Healthy” Source: Larry Smarr, Calit2