Neufeld erin 2012 for posting

Our bodies, our microbes,

ourselves

Extended Learning Opportunities

Erin, Ontario Feb 23, 2012

Twitter @JoshDNeufeld

[email protected]

Diversity of microbial communities Factors (pH, latitude), human microbiome

Rare members, undetected organisms Method development

Linking function and phylogeny Stable-isotope probing and metagenomics

Carbon cycling and biofuel bugs

Discovery of novel N-cycle players Denitrification Nitrification Anammox

Microbial ecology Why is this so hard to study?

Microbiology of you What’s in you and why does it matter?

Today’s lecture – an overview

Thanks

Hand

elsm

an J. 200

7. Encyclope

dia of Life

Scien

ces

1031 Number of microbial cells on Earth 1021 Number of stars in the Universe

1011 Stars in the Milky Way

1010 Microbial cells per gram of soil 1014 Human cells with each human

106 Microbial cells per mL of seawater

107 Viral particles per mL of seawater

Microbial World

1015 Microbial cells with each human

h9p://en

.wikiped

ia.org/w

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I then most always saw,

with great wonder, that in

the said matter there were

many very little living

animalcules, very prettily

a-moving.

Carl Woese, Professor of Microbiology at

the University of Illinois at Urbana-Champaign

One of the first to use

the sequences of ribosome genes for

taxonomy

Bacterial taxonomy became “a field fresh

with the excitement of the experimental

harvest”

“The small subunit ribosomal RNA genes were ideal because of their universal distribu.on, structural conserva.on, the presence of conserved and variable regions, and resistance to lateral gene

transfer” Neufeld and Mohn (2005)

16S rRNA genes Why so ubiquitous for microbial ecology studies?

Bacteria

PROKARYOTES

Archaea Eukarya

EUKARYOTES

Universal ancestor

Diplomonads (Giardia)

Marine Crenarchaeota

Microsporidia

Trichomonads

Flagellates

Ciliates

Plants

Fungi

Animals Entamoebae Slime

molds

Extreme halophiles

Thermoplasma

Methanopyrus Pyrolobus

Pyrodictium

Methanosarcina Euryarchaeota

Crenarchaeota Thermoproteus

Thermococcus

Methano- bacterium

Methano- coccus

Green nonsulfur bacteria

Gram- positive bacteria

Mitochondrion

Chloroplast

Proteobacteria

Flavobacteria Cyanobacteria

Thermotoga

Thermodesulfobacterium

Aquifex

CharacterizaWon of microbial isolates universal phylogeneWc tree

You are here.

Costa Rica b

irds Sampling microbial communiWes is akin to sampling diverse communiWes from other areas of biology.

Sampling is usually done by capturing sequences rather than capturing organisms.

Problem?

Hughes et al. 2001

Sampling microbial communiWes

Microbial ecology Why is this so hard to study?

Microbiology of you What’s in you and why does it matter?

Today’s lecture – an overview

What we’ve learned from ribosomal RNA

surveys of our bodies and the

environment.

Who are we?

Image by Feel MysWc

DISCLAIMER

No medical advice in this talk.

There are more bacteria in your gut than there are people on the planet.

10 bacterial cells : 1 human cell

1 g of feces = 1 million bacteria

Every surface of our body is a niche for microbes

90% microbe, 10% human

100X more microbial genes than human genes

Humans are like “spaceships” for our bugs

Our microbial fingerprint is unique

LocaWon, locaWon, locaWon

Mouth: saliva, tongue, mucosal surfaces, teeth and gums (700 species; 10 phyla)

Esophagus: microbes from oral cavity and upper respiratory tract (95 species; 6 phyla)

Stomach: low numbers; lactobacilli, streptococci, H. pylori (128 species; 8 phyla)

Small intes.ne: -‐  duodenum: not opWmal to colonize -‐  jejunum: increase in streptococci, lactobacilli, Haemophilus, Bacteroides, and Bifidobacteria -‐  ileum: increased numbers, resembles colon

Large intes.ne (colon): -‐  Lumen: anaerobes:aerobes 100-‐1000:1 -‐  Bacteroides, Bifido, Clostridium, Bacillus, Fusobacterium (800 species; 10 phyla)

What role do

microorganisms

play in your body?

Sterile at birth Colonization begins immediately

“Adult” community

by 1 year

Koeniga et al. 2011

Peas and formula

?

AnWbioWcs

1 Supragingival plaque L 2 Subgingival plaque L 3 Supragingival plaque L 4 Supragingival plaque L 5 Tongue biofilm

Mouth

6 Gastric antrum 7 Gastric body 8 Duodenum

Stomach

9 Transverse colon 10 Sigmoid colon 11 Rectum 12 Stool

Colon

5

7

6

8

12

9 10

11

1 2

4 3

Bacteroides

Coprococcus

Faecalibacterium

Blautia

Parvimonas

Streptococcus

Prevotella

HaemophilusVeillonella

Fusobacterium

Neisseria Capnocytophaga

Campylobacter

PC1

(7.9

%)

PC1 (17.0%)

Verrucomicrobia

Acidobacteria

Firmicutes

Bacteriodetes

Cyanobacteria

SR1

Actinobacteria

Proteobacteria

Fusobacteria

TM7Spirochaetes

Tongue plaqueTooth plaqueGastric antrumGastric bodyDuodenum

Transverse ColonSigmoid ColonRectumStool

PhylumGenus

Sample site

Sample location Subject Gender

MouthStomachDuodenumColonStool

Subject 1Subject 2Subject 3Subject 4

FemaleMale

b c d

a

Mouth

Stomach/ Duodenum Colon

Stool

65671523

17333

70171

11269 58

18

64 3

578251

527

Subject 1

Mouth


Stool

6924827

5509

63 110

313 83 49

8

99 15

149466

148

Subject 2

Mouth


Stool

5605176

15523

61 103

167 78 15

7

61 6

276733

70

Subject 3

Mouth


Stool

8164145

34814

18 32

83 70 7

1

100 3

512739

1092

Subject 4

Women

Men

Germ-‐free mouse colonized with microbial community of obese mouse or lean mouse.

Obese mice •  50% lower Bacteroidetes, higher Firmicutes •  Weight loss = increased Bacteroidetes,

decreased Firmicutes Same result found in humans (Turnbaugh et al. 2006)

Gut Microbiome

Ley et al. 2006

Depression

Premysl Bercik, McMaster University (personal communicaWon)

Behaviour

“Intestinal dysbiosis might contribute to psychiatric disorders in patients with

bowel disorders.”

Implications?

Probiotics "Live microorganisms which when administered in adequate amounts confer a health benefit on the host".

Fecal transplants

Fecal transplants have >90% success rate in C. difficile associated disease. How else could they be used? "The potenWal is very high, but the actual amount of research is relaWvely low” -‐Rob Knight

What will we discover next?

Gut Microbiome summary

Over 800 different species, 7000 strains Experimental evidence shows implicaWons in: •  metabolism of carbohydrates (obesity) •  ulcers and Helicobacter pylori predominance •  immune system (allergies, asthma, pathogen defense) •  synthesis of amino acids and vitamins •  deacWvaWng xenobioWcs (carcinogens) •  response to epithelial cell injury (by pathogens) •  colorectal cancer (2nd leading cause of cancer-‐related death) •  inflammatory bowel diseases (Crohn’s and coliWs) •  possible role in mulWple sclerosis, Parkinson’s •  link to depression and behaviour

Turnbaugh et al. 2007

Research in my lab seeks to answer

some of these quesWons

IBS,

depression, periodonWWs

Hygiene hypothesis

"The human microbiome has been selected, and passed from mother to child, because the bacterial genes are helpful, but as a result of modern practices including widespread antibiotics use, caesarean sections, amalgam dental fillings, constant cleansing, clean water, smaller families and transmission of these normal ancestral microbes has changed, and there are consequences. Some consequences might be good, while others could be bad."

Dr. Martin J. Blaser Professor of Microbiology

NYU Langone Medical Center

Implications

Health and disease linked to microbes

Novel treatments can come from microbes

With understanding, we can be in control

What’s next? (invite your help)

Thank you

Extended Learning Opportunities

Erin, Ontario Feb 23, 2012

Twitter @JoshDNeufeld

[email protected]

Neufeld erin 2012 for posting

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