1

Human microbiome research: Present status and possible future directions

Lita M. Proctor, Ph.D. Coordinator, Human Microbiome Project

NHGRI/NIH

ESEH/NAS workshop January 14-15, 2016

Clinically-examined 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

ii. Disease/disorder cohorts: Skin: eczema, psoriasis, acne GI/oral: esophageal adenocarcinoma, necrotizing enterocolitis, pediatric IBS, ulcerative colitis, Crohn’s Disease Urogenital: bacterial vaginosis, circumcision, sexual histories

NIH Human Microbiome Project: $215M investment, a community resource

Phase 1: Survey of the microbiome “Who’s there?”

Phase 2: Integrative HMP “iHMP” what are they doing?

Pregnancy and Preterm Birth: Vaginal & gut microbiomes and host (mother, infant) IBD Onset: GI microbiome and host Type 2 Diabetes Onset: GI & nasal microbiomes and host

i. Healthy cohort: Model human-microbiome conditions:

Longitudinal studies Biological properties of host &

microbiome: Gene expression profiles

Protein profiles Metabolite profiles Other phenotype data

Trans-NIH Microbiome Working Group (TMWG) established 2012

Extramural program staff only, membership from 16 ICOs

LM Proctor (NHGRI), TMWG chair

Mission: Forum for microbiome-related investments at NIH • Identify, gaps, needs, challenges and

opportunities • Share upcoming FOAs, develop joint

FOAs • Coordinate joint funding of

applications • Develop microbiome review panel at

CSR • Serve as central source for external

community

TMWG (external page): www.commonfund.nih.gov/hmp/related_activities

Microbiome Special Emphasis Panel (SEP) Evaluation

Pilot to evaluate need for microbiome-focused review panel at NIH

Small number of FOAs from several ICs assigned to this panel

Test period over three panels in 2015/2016

Evaluation in fall, 2016

https://www.whitehouse.gov/sites/default/files/docs/national_action_plan_for_combating_antibotic-resistant_bacteria.pdf

National Initiative to Curb Antibiotic Resistance (AR)

Some highlights from the US initiative: • Support research on role of the human microbiome in controlling drug-resistant

pathogens.

• Support research on spread of AR genes between zoonotic pathogens and animal & human microbiomes.

• US will work with WHO and other int’l partners on point-of-care diagnostics, vaccines, and drugs to combat AR bacteria.

• US will work with int’l partners to investigate the microbiomes of food animals and spread of AR.

Total Microbiome Research Funding FY12-14 by Agency Total Funding

for FY12-14: $921,786,776

USDA 4%

DOE 15%

NASA 3% DOD 4%

NIH 56%

FDA 2%

USAID, CDC, Smithsonian, <1%

DOI 1%

NSF 11%

NIST, $225,000 (0.02%)

NOAA <1%

EPA 1%

FTAC-MM 2015

FTAC-MM: OSTP charter FY12-14 data call microbiome ‘writ large’ 6 Departments (16 agencies), 4

Independent Agencies, 1 quasi- governmental entity

Data call results: $922M over FY12-14 NIH comprised 56% of this total NSF and DOE comprised an

additional 26% of this total

Nature Microbiology paper:

$922M

FastTrack Action Committee – Mapping the Microbiome (FTAC-MM)

htt

ps:

//w

ww

.wh

ite

ho

use

.go

v/b

log/

20

15

/11

/20

/map

pin

g-e

arth

s-m

icro

bio

me

s

http://dx.doi.org/10.1038/nmicrobiol.2015.15

FTAC-MM portfolio analysis (human studies)

FTAC-MM 2015

Body regions: • GI tract: 55% of total support • Other body sites: 1-13%

Research themes: • Basic biology: 51% • Applied studies: 28% • Tools/ resource development: 21%

http

://dx.d

oi.o

rg/10

.10

38

/nm

icrob

iol.2

01

5.1

5

Precision Medicine Initiative (PMI)

Dr. Jo Handelsman Yale microbial ecologist OSTP Associate Director of Science Youtube video about PMI, including microbiome https://www.youtube.com/watch?v=RIzbg8REzGw

national research cohort, ~ 1,000,000 subjects emphasis on tools for personalized medicine microbiome being considered as a personalized property

PMI announced by President Obama January 30, 2015 https://www.whitehouse.gov/the-press-office/2015/01/30/fact-sheet-president-obama-s-precision-medicine-initiative

Relationship between microbial properties and time

Microbial property to be measured dependent on question

Dietert and Silbergeld, 2015

Silbergeld’s metaphor “The Microbiome as Gatekeeper and Watchman”

Modified from Funkhouser and Bordenstein (2013)

Microbes acquired from the environment. External breast Skin bacteria (Staphylococcus, Corynebacteria, Propionobacteria)

Internal breast Breast milk contains 100-600 OTUs (Streptococcus, Staphylococcus, Serratia, Corynebacteria, Lactococcus, Weisella, Leuconostoc) Gut bacteria transmitted to mammary glands via lymph fluid and blood. External sources include skin and infant mouth.

Amniotic fluid (proposed) Bacteria of oral origin found in amniotic fluid (Fusobacterium, Streptococcus, Bergeryella, Porphyromonas, Rothia, Fifofactor) Oral bacteria transmitted to uterus via blood.

Placenta (proposed) Bacteria found in umbilical cord blood, amniotic fluid, placenta, fetal membranes, meconium (Escherichia, Shigella, Leuconostoc, Enterococcus, Lactococcus) Bacteria transmitted via vagina or blood.

Vagina Bacterial communities in vagina are significantly different in women of different ethnicities and races. Bacterial communities are less diverse during pregnancy and dominated by Lactobacillus.

Farm animals are the most frequent non-human sources for gene exchange with human-associated microbes.

HGT rates are even higher among bacteria from the same body site.

Smillie et al. (2011)

Human microbiome is a ‘hot spot’ for horizontal gene transfer and it’s not just about antibiotic

resistance.

HG

T/1

00

co

mp

aris

on

s

• What should be done next? What set of questions should be explored to better

understand whether and to what extent the microbiome plays a role in biological response to environmental exposures?

• How can we incorporate aspects of microbiome research into epidemiologic or occupational studies?

• How should microbiome researchers be encouraged to design their research and report their data so that it addresses implications of environmental and occupational exposures and is useful to agencies/stakeholders as they consider risk?

• What could institutions do now to move the field forward? Does the research community need to work with funding agencies to make sure future study sections and peer reviewers are cognizant of and prepared for this emerging area?

Round table questions