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Toward Personalized Nutrition for the Host and its Microbiome


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

Published in: Food
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Toward Personalized Nutrition for the Host and its Microbiome

  1. 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 1
  2. 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. 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. 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. 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. 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. 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
  8. 8. “Non-caloric artificial sweeteners (NAS) are among the most widely used food additives worldwide.”
  9. 9. 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
  10. 10. ● 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
  11. 11. 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
  12. 12. The Coupled Neural, Immune, and Microbiome Systems Provide a Model Explaining How Nutrition Can Alter Neurodevelopment 2017
  13. 13. 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
  14. 14. 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
  15. 15. 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)
  16. 16. 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
  17. 17. 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)
  18. 18. 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
  19. 19. 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
  20. 20. 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.”
  21. 21. 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.
  22. 22. 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
  23. 23. Adding Vegetable Fiber to the Diet Seems to Counter Obesity By Increasing Microbiome Diversity
  24. 24. 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
  25. 25. Aligning Your Eating Pattern With Your Body’s Circadian Rhythm Is As Important As What You Eat
  26. 26. 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
  27. 27. 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,
  28. 28. 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, Time of Day
  29. 29. Personalized Nutrition Companies Based on Human DNA, Blood Biomarkers, and/or Microbiome
  30. 30. 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