1. 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

4. ~10 million microbial species on Earth, most which are beneficial
Catalysts for creation of the NIH Human Microbiome Project
Infectious diseases Autoimmune diseases
Bach, 2002
~1400 human pathogens
vs.
~10 million microbial species on Earth, most which are beneficial
Follow on to Human Genome Project

5. Phase 1: Survey of the microbiome in humans
Human Microbiome Project ( ): a community resource (
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
18-40 y.o.
5 major body regions
(18 body sites)
Up to 3 visits in 2 yrs
No antibiotics, probiotics, immunomodulators
Microbiome-associated conditions
Skin: eczema, psoriasis, acne
GI/oral: esophageal adenocarcinoma, necrotizing enterocolitis, pediatric IBS, ulcerative colitis, Crohn’s Disease
Urogenital: bacterial vaginosis, circumcision, sexual histories

6. NIH Human Microbiome* Project (2008-2012)
(Canada)
Sequencing Centers
Demonstration Projects
Data Analysis & Coordination Center
Technology Development
Computational Tools
ELSI
Clinical labs
* Human microbiome: full complement of microbes living in/on the human body and their collective genes & genomes.

7. In healthy American adults, the microbial community composition in each part of the body is unique.
PCoA2 (4.4%)
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.
Human Microbiome Project Consortium (2012a)

8. In fact, microbial composition of healthy adult microbiomes
is highly variable.
Yet, genetic potential of each microbiome is less variable.
Microbial metabolic pathways of each body site community
Airway Skin Oral (1) Oral (2) Oral (3) GI Tract Urogenital
Microbial composition of each body site community
Phylum level
The healthy cohort subjects exhibited great variability in the microbiome composition but not in genetic potential for metabolic properties. Perhaps the core property we are looking for is reflected in the metabolic properties of the microbial communities.
A ‘core’ microbial composition may not occur with host phenotype.
However, a ‘core’ metagenomic and/or functional profile may occur with host phenotype.
Subject
Proportion
Human Microbiome Project Consortium (2012b)

9. Microbial composition may not be the property of interest
Microbiome Property
Variability betw. subjects
10 most abundant microbial taxa in metagenomes of subjects in cohort
Variable
10 most abundant microbial metabolic genes in metagenomes of subjects in cohort
Not variable
E.C. categories
10 most abundant expressed microbial metabolic genes in metatranscriptomes of subjects in cohort
E.C. categories
Variable
Franzosa et al. 2014

10. 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?

11. Phase 2: Integrative HMP “iHMP” what are they doing?
Human Microbiome Project ( ): a community resource (
Phase 2: Integrative HMP “iHMP” what are they doing?
$25M, Common Fund & NIDDK + ORWH + NCCAM + ODS
Biological properties of both microbiome and the host
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

12. 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)

13. Cell Host & Microbe, Sept. 2014, vol. 16, issue 3
iHMP marker paper
Cell Host & Microbe, Sept. 2014, vol. 16, issue 3
(open access)
iHMP marker paper describes:
3 longitudinal cohort studies & their hypotheses
sampling protocols for both microbiome and host
different ‘omics data being collected
where these data will be deposited

14. Dynamics of Pregnancy and Preterm Birth Study

15. Dynamics of Onset of Inflammatory Bowel Diseases

16. Dynamics of Type 2 Diabetes Onset

17. Integrative HMP website (http://hmp2.org)

19. Questions?