The NIH Human Microbiome Project
Lita M. Proctor, Ph.D.
Coordinator, Human Microbiome Project
National Human Genome Research Institute, NIH
(+ the work of hundreds of scientists in US and abroad)
The Forum for Medical Affairs
Dallas, TX
November 9, 2014
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Catalysts for creation of the NIH Human Microbiome Project
Autoimmune diseases
Bach, 2002
Infectious diseases
~1400 human pathogens
vs.
~10 million microbial species on
Earth, most which are beneficial
Follow on to Human Genome Project
Human Microbiome Project (2008-2012): a community resource
(http://commonfund.nih.gov/hmp)
Phase 1: Survey of the microbiome in humans
“Who’s there?”
$175M: Common Fund & cofunding from NHGRI + NIAID + NIDDK + NIDCR + NIAMS +
ORWH + NCCAM + ODS
Is there a “core” microbiome?
Healthy cohort study
Demonstration Projects
Clinically healthy
300 male/female
Microbiome-associated
conditions
Skin: eczema, psoriasis, acne
18-40 y.o.
5 major body regions
(18 body sites)
Up to 3 visits in 2 yrs
No antibiotics, probiotics,
immunomodulators
GI/oral: esophageal
adenocarcinoma, necrotizing
enterocolitis, pediatric IBS,
ulcerative colitis, Crohn’s
Disease
Urogenital: bacterial vaginosis,
circumcision, sexual histories
NIH Human Microbiome* Project (2008-2012)
(Canada)
* Human microbiome: full complement of
microbes living in/on the human body and
their collective genes & genomes.
Sequencing Centers
Demonstration Projects
Data Analysis & Coordination Center
Technology Development
Computational Tools
ELSI
Clinical labs
PCoA2 (4.4%)
In healthy American adults, the microbial community
composition in each part of the body is unique.
PCoA1 (13%)
 For each person, est. 1,000 bacterial species and 2,000,000 bacterial genes.
 Total pool, est. 10,000 species and 8,000,000 genes.
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Human Microbiome Project Consortium (2012a)
In fact, microbial composition of healthy adult microbiomes
is highly variable.
Yet, genetic potential of each microbiome is less variable.
Microbial composition of each body site community
Airway
Skin
Oral (1)
Oral (2)
Oral (3)
GI Tract
Urogenital
Phylum level
Proportion
metabolic pathways
of eachmay
bodynot
siteoccur
community
AMicrobial
‘core’ microbial
composition
with host phenotype.
However, a ‘core’ metagenomic and/or functional profile may occur
with host phenotype.
Human Microbiome Project Consortium (2012b)
Subject
Microbial composition may not be the property of interest
Microbiome Property
E.C. categories
E.C. categories
10 most abundant
microbial taxa in
metagenomes of
subjects in cohort
Variability betw. subjects
Variable
10 most abundant
microbial
metabolic genes in
metagenomes of
subjects in cohort
Not variable
10 most abundant
expressed microbial
metabolic genes in
metatranscriptomes
of subjects in cohort
Variable
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Franzosa et al. 2014
Recall: the metagenome is the genetic “blueprint” of the
microbiome.
metabolism
What biological properties do
we need, to understand the role
of the microbiome in the
human:
transcripts?
proteins?
metabolites?
Human Microbiome Project (2013-2016): a community resource
(http://hmp2.org)
Phase 2: Integrative HMP “iHMP” what are they doing?
 $25M, Common Fund & NIDDK + ORWH + NCCAM + ODS
Biological properties of both microbiome and the host
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microbial composition & gene expression, proteins and metabolites
from microbiome and host
longitudinal cohort studies
integrated datasets of these properties as a community resource
Exemplar microbiome-associated human
conditions:
Dynamics of Pregnancy and Preterm Birth:
Vaginal & gut microbiomes and host (mother, infant) properties
Dynamics of IBD Onset:
GI microbiome and host properties
Dynamics of Type 2 Diabetes Onset:
GI & nasal microbiomes and host properties
NIH Human Microbiome Project (2013-2016)
iHMP Research Consortium (15 institutions)
Pregnancy & Preterm Birth study: Buck/Strauss/Jefferson (VCU)
IBD onset study: Xavier/Huttenhower (Broad, Harvard)
T2D onset study: Snyder/Weinstock (Stanford, Jackson Lab)
iHMP Data Analysis and Coordination Center: White (Univ MD)
iHMP marker paper
Cell Host & Microbe, Sept. 2014, vol. 16, issue 3
(open access)
iHMP marker paper describes:
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3 longitudinal cohort studies & their hypotheses
sampling protocols for both microbiome and host
different ‘omics data being collected
where these data will be deposited
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Dynamics of Pregnancy and Preterm Birth Study
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Dynamics of Onset of Inflammatory Bowel Diseases
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Dynamics of Type 2 Diabetes Onset
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Integrative HMP website (http://hmp2.org)
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Questions?
lita.proctor@nih.gov
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