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 AffairsDallas, TX

November 9, 2014 1

2

~1400 human pathogensvs.

~10 million microbial species on Earth, most which are beneficial

Follow on to Human Genome Project

Catalysts for creation of the NIH Human Microbiome Project

Bach

, 200

2

Infectious diseases Autoimmune diseases

Demonstration ProjectsHealthy cohort study

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

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?

NIH Human Microbiome* Project (2008-2012)

(Canada)

Sequencing CentersDemonstration ProjectsData Analysis & Coordination CenterTechnology DevelopmentComputational ToolsELSIClinical labs

* Human microbiome: full complement of microbes living in/on the human body and their collective genes & genomes.

In healthy American adults, the microbial community composition in each part of the body is unique.

Human Microbiome Project Consortium (2012a)

PCoA

2 (4

.4%

)

PCoA1 (13%)

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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.

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

In fact, microbial composition of healthy adult microbiomes is highly variable.

Yet, genetic potential of each microbiome is less variable.

Subject

Prop

ortio

n

Human Microbiome Project Consortium (2012b)

A ‘core’ microbial composition may not occur with host phenotype.

However, a ‘core’ metagenomic and/or functional profile may occur with host phenotype.

Phylum level

9Franzosa et al. 2014

10 most abundant microbial taxa in metagenomes of subjects in cohort

10 most abundant microbial metabolic genes in metagenomes of subjects in cohort

10 most abundant expressed microbial metabolic genes in metatranscriptomes of subjects in cohort

Microbial composition may not be the property of interest

E.C.

cat

egor

ies

E.C.

cat

egor

ies

Variable

Microbiome Property Variability betw. subjects

Not variable

Variable

metabolism

What biological properties do we need, to understand the role of the microbiome in the human:

transcripts?proteins?metabolites?

Recall: the metagenome is the genetic “blueprint” of the microbiome.

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

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 microbial composition & gene expression, proteins and metabolites

from microbiome and host longitudinal cohort studies integrated datasets of these properties as a community resource

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)

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iHMP marker paperCell 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

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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