connecting body time series to macro body changes

“Connecting Body Time Series

to Macro Body Changes”

The American Academy of Osteopathy 2017 Convocation

The Balance Point: Bringing the Science and Art of Osteopathic Medicine Together

Breakout Session

Colorado Springs, CO

March 24, 2017

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.net1

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

Think of These Phyla of Animals When

You Consider the Biodiversity of Microbes Inside You

Phylum

Annelida

Phylum

Echinodermata

Phylum

CnidariaPhylum

Mollusca

Phylum

Arthropoda

Phylum

Chordata

Phylum

Porifera

Results Include Relative Abundance of Hundreds of Microbial Species

Average Over 250 Healthy People

From NIH Human Microbiome ProjectNote Log Scale

Clostridium difficile

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)

LS Abrupt Change in Weight and in Symptoms

January 1, 2014

Lialda

Uceris

Frequent IBD Symptoms

Weight Loss

Few IBD Symptoms

Weight Gain

Source: Larry Smarr, UCSD

My Microbiome Ecology

Time Series Over 3 Years

Source Justine Debelius, Knight Lab, UC San Diego

Coloring Samples Before (Blue) and After (Red) January 2014

Reveals Clustering


An Apparent Sudden Phase Change Occurs


Larry Smarr Gut Microbiome Ecology Shifted After Drug Therapy

Between Two Time-Stable Equilibriums Correlated to Physical Symptoms

Lialda

&

Uceris

12/1/13 to 1/1/14

12/1/13-

1/1/14

Frequent IBD Symptoms

Weight Loss

5/1/12 to 12/1/14Blue Balls on Diagram

to the Right

Few IBD Symptoms

Weight Gain

1/1/14 to 1/1/16

Red Balls on Diagram

to the Right

Principal Coordinate Analysis of

Microbiome Ecology

PCoA by Justine Debelius and Jose Navas,

Knight Lab, UCSD

Weight Data from Larry Smarr, Calit2, UCSD

An

tib

ioti

cs

Prednisone

1/1/12 to 5/1/12

5/1/12

Weekly Weight (Red Dots Stool Sample)

Few IBD Symptoms

Weight Gain

1/1/14 to 1/1/16

Red Balls on Diagram

to the Right

20 Years of Smarr’s Fasting Glucose:

Directional Shift at Same Time as Weight Gain and Microbiome Ecology Shift

Glucose Best Range

70 to 100

Prediabetes Range

100 to 125

Weight gain started

Microbiome Ecology Highly Disrupted

by Medical Interventions

Colon Cleanse

Colon Cleanse

Antibiotics

Data from Dr. Embriette Hyde,

Rob Knight Group, UCSD

July 2015 Colonoscopy November 2016 Colonoscopy

Phylum Level Changes

Associated with Colonoscopy and Surgery

Pre-

colonoscopy

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Bacteroidetes Firmicutes Proteobacteria Verrucomicrobia Cyanobacteria Fusobacteria

Pre-

colonoscopyPost-colonoscopy Pre-

colonoscopyPost-colonoscopy Post-

surgery

July 2015 November-December 2016

Data from Dr. Embriette Hyde,

Rob Knight Group, UCSD

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

EGG Array in UCSD Professor Todd Coleman’s Lab

Experiment with PhD Student Armen Gharibans

2 Days After Surgery 2 Weeks After Surgery1 Week Before Surgery

Stomach (0.05 Hz) Small Intestines (0.18 Hz)

Colon

Sigmoid Blockage

Using EGG to Separate Out

the Components of the GI Tract

Source: Armen Gharibans, UCSD

GI Hyper-Activity Passed Gas 1st Bowel Movement

2nd Night of Sleep 3rd Night of Sleep

Return to normal

High power, irregular Low power, periodic Low power, regular

48 Hours EGG on Larry Smarr:

When Does the Colon Restart After Surgery?

Source: Armen Gharibans, UCSD; Analysis by Benjamin Smarr, UCB

Carcinoembryonic Antigen (CEA) Screening Test for Cancer

Was Elevated and Increasing, Dropped After Surgery, But Is Now Increasing

85% of Healthy People 95% of Healthy People

Ranges from Exeter Clinical Labs www.exeterlaboratory.com/test/carcinoembryonic-antigen-cea/

Post-Surgery

Colonoscopy Images Show Inflamed Pseudopolyps

in 6 inches of Sigmoid Colon Over Six Years

Dec 2010 Jan 2012 Nov 2016

Note how the one polyp gets progressive bigger

and then grows a twin…

Pathology Report on Resected Colon:

“No Dysplasia Identified”