Keynote Forum on the Future of Food, Health and Nutrition University of California, Davis Davis, CA May 1, 2018

1. “Toward Personalized Nutrition
for the Host and its Microbiome”
Keynote
Forum on the Future of Food, Health and Nutrition
University of California, Davis
Davis, CA
May 1, 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
1

2. Abstract
The things we ingest orally, whether food or pharmaceuticals, cause a dynamic evolution of
our gut microbiome, which in turn impacts our health. Mammals have trillions of microbes
inhabiting their GI tract, forming a highly diverse ecology. This gut microbiome is coupled to
all the other organs in the body in multiple ways. New research discoveries demonstrate
that a variety of processed food additives can disrupt the microbiome. I will illustrate
microbiome impacts with experiments I have run on my own body. This new research is
illuminating the coming disruptive transition to personalized nutrition, tuned to the state of
our body and its microbiome.

3. To Understand the Impact of Food on Health and Disease
We Must Consider the Human Microbiome
Inclusion of the “Dark Matter” of the Body
Will Radically Alter Medicine and the Food Industry
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

4. 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

5. 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

6. Are Changes in Our Microbiome Ecology Driving The Multi-Decadal Increase
In Autoimmune and Other Non-Communicable Diseases?
Bach (2002) N Engl J Med, Vol. 347, 911-920
2014

7. Could the Gut Microbiome Ecology Changes Shed New Light On
The Obesity/Metabolic Syndrome Public Health Emergency?
% Obese
100 Million American Adults
Have Diabetes or Prediabetes
- CDC 2017

9. “Non-caloric artificial sweeteners (NAS) are among
the most widely used food additives worldwide.”

11. Sebastian E. Winter, Christopher A. Lopez
& Andreas J. Bäumler,
EMBO reports v.14, p. 319-327 (2013)
Inflammation Enables Anaerobic Respiration Which Leads to Dysbiosis:
Phylum-Level Shifts in the Gut Microbiome Ecology

12. ● Metabolic Network for Central
Metabolism in E.coli
● Other Metabolic Pathways
Not shown:
○ Amino Acid Metabolism
○ Fatty Acid Metabolism
○ Nucleotide Metabolism
○ ……
● Metabolic Network Varies For
Different Strains
King et al. PLOS Computational Biology (2015)
Ubiquinone Reduction/Oxidation
Menaquinone Reduction/Oxidation
Demethylmenaquinone Reduction/Oxidation
Nitrate Reductase
TCA cycle
Glycolysis & Gluconeogenesis
Pentose Phosphate
Pathway
Fermentation
UC San Diego Has Constructed Genome-Wide Metabolic
Computational Models for 110 E. Coli Strains (including 54 IBD isolates)
Bernhard Palsson Systems Biology
Research Group-UC San Diego

13. The Microbiome–Gut–Brain Axis Connects Altered Microbiome Ecology
To Shifts in Behavior and Disease Throughout the Body
Source: Montiel-Castro, et al.
Frontiers in Integrative Neuroscience 2013

14. The Coupled Neural, Immune, and Microbiome Systems
Provide a Model Explaining How Nutrition Can Alter Neurodevelopment
2017

15. Since Humans Are Not Mice, I Have Been Tracking My Internal Biomarkers For A Decade
To Understand My Body/Microbiome Dynamics
My Quarterly
Blood DrawCalit2 64 Megapixel VROOM

16. Only One of My Blood Measurements
Was Far Out of Range--Indicating Chronic Inflammation
Normal Range <1 mg/L
27x Upper Limit
Complex Reactive Protein (CRP) is a Blood Biomarker
for Detecting Presence of Inflammation

17. Longitudinal Stool Tests Revealed Large Excursions in My Immune System:
Inflammatory Bowel Disease
Normal Range
<7.3 µg/mL
124x Upper Limit for Healthy
Lactoferrin is a Protein Shed from Neutrophils -
An Antibacterial that Sequesters Iron
Typical
Lactoferrin Value for
Active Inflammatory
Bowel Disease
(IBD)

18. I Have Been Collaborating with the UCSD Knight Lab
To Analyze My Gut Microbiome Dynamics
Larry’s 40 Stool Samples Over 3.5 Years
to Rob’s lab on April 30, 2015

19. Lessons from Ecological Dynamics:
Gut Microbiome Has Multiple Relatively Stable Equilibria
“The Application of Ecological Theory Toward an Understanding of the Human Microbiome,”
Elizabeth Costello, Keaton Stagaman, Les Dethlefsen, Brendan Bohannan, David Relman
Science 336, 1255-62 (2012)

20. PCoA by Justine Debelius and Jose Navas,
Knight Lab, UCSD
My Gut Microbiome Ecology Shifted After Drug Therapy
Leading to Rapid Weight Gain, But Drop in IBD Symptoms
Lialda &
Uceris
12/1/13
to
1/1/14
12/1/13-
1/1/14
Frequent IBD Symptoms
Weight Loss
7/1/12 to 12/1/14
Blue Balls on
Diagram to the Right
Principal Coordinate Analysis of
Microbiome Ecology
Weight Data from Larry Smarr, Calit2, UCSD
Weekly Weight
Few IBD Symptoms
Weight Gain 1/1/14 to 8/1/15
Red Balls on
Diagram to the Right

21. My Fasting Glucose Level Began to Rise
After the Microbiome Shift – I Had Developed Prediabetes
Glucose Best Range
70 to 100
Prediabetes Range
100 to 125
Weight gain startedDiabetes Range

22. Can We “Garden” Our Way Back to Health?
New 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.”

23. 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

24. Fecal Transplants in Pill Form
For Your Pets Are Already Available
Spinout of
“Based on our research, we have found that many pet digestive
disorders are linked to low bacterial diversity in the gut.”
--AnimalBiome CEO Holly Ganz

25. Adding Vegetable Fiber to the Diet
Seems to Counter Obesity By Increasing Microbiome Diversity

26. Can I Increase My Microbiome Diversity
By Consuming 3 Dozen Plant Species Per Day?
UC San Diego’s Rob Knight Lab is Currently
Sequencing 100 Days of My Stool Samples
I Also Have Photos of Everything I Consumed

27. Aligning Your Eating Pattern With Your Body’s Circadian Rhythm
Is As Important As What You Eat

28. I Volunteered to Become a Patient in the UCSD/Salk Pilot Study
of Time-Restricted Eating (TRE) in Metabolic Syndrome
28
– Hypothesis
– In patients with metabolic syndrome who eat for
≥ 14 hours per day, limiting daily oral intake
to 10 hours per day for 3 months while
using a smartphone application will result in:
– Weight loss
– Improved glucose metabolism
– Improved biomarkers associated with
cardiovascular disease risk
– First study of TRE in metabolic syndrome
– First use of continuous glucose monitoring during TRE
Pam Taub, MD
Cardiology
Satchin Panda, PhD
Circadian Biology

29. Pre Post
Days
1 2 3 4 5 6 7 8 9 10 11
Glucose
(mg/dL)
Glucose
(mg/dL)
Days
1 2 3 4 5 6 7 8 9
Time-Restricting My Food Intake to Ten Hours
Improved My Glucose Spiking Without Changing Diet
Data from Taub/Panda Clinical Trial
Graphics by Azure Grant, QuantifiedSelf.com

30. Pre Post
Days
Days
Days123456789
Days
8am 4pm 12am 8am
Time of Day
1234567891011
8am 4pm 12am 8am
Heat Map of Continuous Glucose Monitor Every 5 Minutes
Before and After 3 Months of Time-Restricted Eating
10-Hour
Eating Window
• Other Improvements:
– Waist 108cm to 102 cm
– Weight 197 to 189
– Blood Pressure 140/74 to 130/69 Data from Taub/Panda Clinical Trial
Graphics by Azure Grant, QuantifiedSelf.com
Time of Day

31. Personalized Nutrition Companies
Based on Human DNA, Blood Biomarkers, and/or Microbiome

32. UC San Diego Is Carrying Out Detailed Input/Output Research
Connecting Metagenomics and Metabolomics of Food and Gut Microbiome
Projects Leaders: Julia Gauglitz, Rob Knight, Pieter Dorrestein, Rachael Dutton, UC San Diego