Toward understanding the symbiotic role of microbial communities in - - PowerPoint PPT Presentation

Ma ría Glo ria Do míng ue z-Be llo

NYU Sc ho o l o f Me dic ine

Toward understanding the symbiotic role of microbial communities in human biology

“First picture of Earth from the surface of Mars” NASA’s Curiosity rover, Jan 31st 2014

Origin

• f Earth

4.8 billion years ago Origin

• f first life

3.8 billion years ago Multicelular life 2.1 billion years ago Eukaryotes Homo sapiens 0.2 million years ago

BACTERIA

Biology-driven evolution

Costello et al. 2009 Science

Body niches for the human microbiome

Epithelia covers animal bodies

Vaginal seeding skin- oral + strict milk

Newborn 1 month 2 months 4 months 7 months

Developmental exposures and selection pressures

Environmental

0-6 months >6 months

Maternal

Vaginal seeding skin- oral + strict milk

Newborn 1 month 2 months 4 months 7 months

Developmental exposures and selection pressures

0-6 months >6 months

The New Yorker, Nov 4, 2015

Developmental exposures 1-MOM 2-MILK 3-BUILT ENVIRONMENT

The primate tree of life and hominid subsistence

(8) (6) (2.5) (4) (0.2) (15) (Million years ago)

p

Gatherers - Hunters Gatherers

Features that made us human:

(8) (6) (2.5) (4)

Gatherers

(0.2) (15) (Million years ago)

Bipedalism Cooperativism Gatherers - Hunters

p

4 2.5 0.2 M years of common ancestor

Gatherer

Bipedalism and pelvis constraints

• D. Lieberman, 2013

Cooperation and brain size

• D. Lieberman, 2013

Big head + Narrow pelvis

~15% births

C-section and maternal mortality

The Economist, August 2015

C-section rates variation in Europe, 2010

C-section rate changes in Sweden and the USA

SWEDEN USA

1996 2009 2012

17% (2008) 30% (2008)

USA

Effect of delivery mode

• n the neonate’s primary microbiota?

Acquisition of maternal vaginal microbiota

1 2 3 4 Mother-baby pair

PNAS 2010

PNAS 2010

Mode of birth and primary microbiota

Va g ina l C-se c tio n

Mode of birth and primary microbiota

PNAS 2010

Va g ina l C-se c tio n

Mode of birth and primary microbiota

PNAS 2010

?

Bacterial source: the built environment?

Hakdong Shin New York Univ. Humberto Cavallin

• Univ. Puerto Rico

Shin et al 2015 PloS One

(***, p<0.001)

• Unweighted
• 1,000 seqs/sample
• Closed-reference OTU picking

Human skin bacteria in Operating Room dust

PC2 (6%) PC1 (16%) Operating room samples (n=30) HMP_Skin (n=2,199) HMP_Oral (n=3,695) HMP_Vaginal (n=564) HMP_Stool (n=437)

Distances between groups

Unweighted UniFrac Distance

OR samples vs

HMP_Skin HMP_Oral HMP_Vaginal HMP_Stool

0.6 0.8 1.0

*** *** ***

Shin et al 2015 PloS One

Human skin flakes in Operating Room dust

10 um 10 um 10 um 10 um 10 um 10 um

Positive control OR swabs Negative control H/E staining Pan-cytokeratin

Shin et al 2015 PloS One

Restoring the microbiome

• f C-section newborns

Kassandra de Jesus Lavoy Nora Henderson Sukhleen Bedi NYU

Vaginal source C-section

C-section + vaginal gauze

C-section

Vaginal seeding of babies born by C-section

Dominguez-Bello et al 2016 Nature Medicine

Vaginal seeding of babies born by C-section

Inclusion criteria for patients in the clinical study

• Scheduled C-section

(maternal choice, previous C-section or malposition presentation)

• Healthy mothers with healthy pregnancy
• Negative for HIV, Group B Streptococcus (GBS),

active primary herpes, gonorrhea, chlamydia and

• ther STDs, bacterial vaginosis
• Vaginal pH ≤ 4.5 at time of delivery

Beta diversity of vaginal gauze microbes in relation to maternal body sites

Dominguez-Bello et al 2016 Nature Medicine

Bacterial sources in the first month of life

Vaginal delivery Exposed C-section (n=7) (n=4) (n=7)

Dominguez-Bello et al 2016 Nature Medicine

Vaginal delivery Exposed C-section (n=7) (n=4) (n=7)

Bacterial sources in the first month of life

Dominguez-Bello et al 2016 Nature Medicine

Days

Proportion of bacterial taxa in the first month of life

Dominguez-Bello et al 2016 Nature Medicine

Sp Sp Sp La La La La La La La La La La S24-7 S24-7 S24-7 S24-7 S24-7 S24-7 Ba Ba Ba Ba Ba Ba Ba Ba Sp Sp Sp

Days

Proportion of infant bacterial taxa in the first month of life

DELIVERY

Dominguez-Bello et al 2016 Nature Medicine

Restoration of some bacterial taxa at age 1 month

Dominguez-Bello et al 2016 Nature Medicine

Does “seeding” of C-section babies protect from C-section associated diseases

?

Obesity

Huh, Rifas-Shiman, et al. 2012 Blustein et al. 2013 Mueller et al 2014

Asthma

Kero, Gissler et al. 2002 Kero et al. 2002 Thavagnanam et al. 2007 Roduit et al. 2009 Couzin-Frankel 2010 Ege et al. 2011 Azad et al. 2012

Celiac disease

Decker, Engelmann et al. 2010 Marild, Stephansson et al. 2012

Type 1 diabetes

Algert, McElduff et al. 2009 Aumeunier, Grela et al. 2010 Bonifacio et al. 2012

Diseases associated with C-section

Growing incidence of immune disorders in developed countries

Bach 1999

VD

n=13

CS

n=10

Infant age (mo)

p=0.970 p=0.555 p=0.702 p=0.121 p=0.015 p=0.211 p=0.132 p=0.310 p=0.176 p=0.012 p=0.985 p=0.692 p=0.833 p=0.811 p=0.500 p=0.193 p=0.149 p=0.190 p=0.400 p=0.929

PD Whole Tree Observed Species

Infant microbiome diversity variation with age

70% 70%

Infants not exposed to antibiotics

ECAM study Blaser group

Gut Mic ro b io ta fo r He a lth Summit Ba rc e lo na , Ma rc h 14-15. Pa ine e t a l 1998, E c o syste ms

Re silie nc e E xtinc tio ns E xtinc tio ns

Is the urbanite microbiome impacted?

Yatsunenko et al 2012, Nature

Fecal microbiota diversity in three human populations

Adults Babies <6-months

Most Isolated peoples

Photo: Maria G Dominguez-Bello

Contemporary tribal cultures

1975 2008

Uncontacted peoples

Brazil Paraguay Venezuela

Yanomami village – first contact

Photos: Oscar Noya 2008

Westernization

Gut microbiome diversity across cultures

Clemente et al. 2015 Science Advances

Westernization

Gut microbiome diversity across cultures

Clemente et al. 2015 Science Advances

HUMAN MICROBIOME PROJECT

The New Yorker, Nov 4, 2015

Developmental exposures 1-MOM 2-MILK 3-BUILT ENVIRONMENT

Developmental exposures

VS

Developmental exposures

VS

MICROBES ACROSS CULTURES

Home bacterial composition differs by urbanization level

Ruiz et al 2016 Science Advances

Bacterial communities of wall-floors converge with urbanization

Ruiz et al 2016 Science Advances

Wall bacteria in house spaces

Ruiz et al 2016 Science Advances

Houses

Reduced maternal Transmission Reduced exposure to environmental microbes Reduced microbiota diversity Increased chronic immune diseases

Changes in developmental exposures

Origin

• f Earth

4.8 billion years ago Origin

• f first life

3.8 billion years ago Multicelular life 2.1 billion years ago Eukaryotes Homo sapiens 0.2 million years ago

BACTERIA

Biology-driven evolution

Culture-driving evolution

Origin

• f Earth

4.8 billion years ago Origin

• f first life

3.8 billion years ago Multicelular life 2.1 billion years ago Eukaryotes Homo sapiens 0.2 million years ago

BACTERIA

Biology-driven evolution

Urbanite

Culture-driving evolution

Origin

• f Earth

4.8 billion years ago Origin

• f first life

3.8 billion years ago Multicelular life 2.1 billion years ago Eukaryotes Homo sapiens 0.2 million years ago

BACTERIA

Biology-driven evolution

30,000 y

Urbanite

Evolution turns the inevitable into a necessity

Jacques Monod

Supporting team

Se Jin Song

• Univ. Colorado

Hakdong Shin NYU Marina Hoashi NYU Jose CLemente Mount Sinai S.M.

Alfred P. Sloan Foundation Emch Research Fund C&D Research Fund

Rob Knight UCSD Kassandra de Jesus Laboy Ana Maldondado Albertorio Juan L Rivera Correa Jean Frances Ruiz Selena Rodriguez Univ Puerto Rico Carlos Lopez Noraliz Garcia Univ Puerto Rico Oscar Noya Central Univ. of Venezuela

Sloan project team, Peru-Brazil, USA

Henrique Pereira

• Univ. Fed Amazonas

Atila Novoselac

• Univ. Texas-Austin

Luciana Paulino Humberto Cavallin Univ Puerto Rico Martin Blaser NYU