The microbiome : An introduction - PowerPoint Presentation

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The microbiome: An introduction

Dr Christine K. ChegeMicrobiome SymposiumKenya Paediatric Association Annual Conference10th April 2019

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Definition of microbiome

The collective genomes of microbes that live in and on the human body“ the ecological community of commensal, symbiotic and pathogenic microorganisms that literary share our body space and have long been ignored as determinants of health and disease”

So what is

microbiota

?

Community of microbes living in harmony with human cells

Molecular biologist and Nobel laureate

Joshua Lederberg 2001

We have evolved together!

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In and on you!...and even around you: “the microbial cloud”

Most found here

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Important role in health and disease

Linked to :Obesity

Malnutrition

Heart disease

Diabetes

Some

cancers

Coeliac

disease

Eczema

Asthma

Autoimmune disease

Autism

And more………

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Influence on the immune system

Particularly important in adaptive immune system development in early childhoodhelps in development of tolerance implications on future allergic, inflammatory and autoimmune disorders

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Influence on behavior?

Lets blame lactobacillus

Gut brain axis via the

vagus

nerve

Study done on cowardly

vs

risk-taking miceRead about it here

Association of functional gut disorders with psychiatric disorders

https://www.ncbi.nlm.nih.gov/pubmed/21683077

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How much of us is microbiota?

Previously thought -10 X more microbes than human cells; recently closer to 1:1(39 vs 30 trillion)

100X more genomic content than human genome

1-3% of body’s mass

1-2kg (like your brain….or more )

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BUGS

BRAIN

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Terminologies we need to know

Flora: old name; forget itDiversity: measure of how many different species and how evenly distributed in a microbiomeDysbiosis: imbalance in the microbial communities; associated with disease – this is the rest of the track…

Phenotype:

observable trait(appearance or

behaviour

)determined by genesEnterotype:

collection of species of microbes in the gut microbiome

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The -omes, -

omicsMetabolomeCollection of metabolites from metabolic reactions in a cell, tissue or organismMetatranscriptome

Collection of mRNA molecules expressed from genes in the

microbiota

Proteome

Complete set of proteins expressed by an organism

New

suffix in biology – describes large scale data

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Short history of microbiome research

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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

The father of microbiome

compared his

faecal

and oral

microbiota

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Other key milestones

1885: E. coli from stools of newborns in Germany; Theodor Escherich(yeah…of course)1908: Russian Zoologist, Elie Metchnikoff – posited that health could be enhanced by friendly bacteria in yoghurt1959: rearing of germ free lab animals in ‘gnobiotic

facilities’ to study effect of microbe free living

1970

: Thomas Lucky estimated 100 billion microbes per gram of

faeces

1995: sequencing of the H. influenza genome1996:

16S rRNA sequencing of first human faecal sample

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More recent Advances

2005: bacteria in amniotic fluid of babies born via CS2007: Human microbiome project(HMP) launched2009: study showing association between gut microbiome and disease is launched

2012:

HMP unveils first map of microbes inhabiting health humans

2018:

American Gut Project publishes largest study on

microbiome; over 11000 participants; over 40 diverse countries

Fast forward……

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Microbiome

classification

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A sample of the key players

Bacteroidetes: most prevalent bacteria in gut; produce favourable metabolites that have anti-inflammatory effectsBifidobacterium: early life colonizer;found in gut, mouth, vagina; modulate immune functions; reduced levels in IBD

Lactobacillus:

mouth, gut, vagina;

antidiarrhoeal

propertiesPrevotella

: mouth, gut; metabolic processing

Potential pathogens: pseudomonas, streptococcus

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Microbiome analysis

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metagenomics

Allows study of unculturable microbesGenetic analysis and functional expression screening of microbial communities – microbes are interdependentGives broader description than just species identificationCataloging of microbiome from people of different geographical regions, body systems – microbial diversity studiesSequencing technology using known DNA markers16S rRNA example – all microbes have this gene but unique DNA sequence; closely related microbes show more similarities

Study of the

complete genome of every microbe in a sample

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Microbial community DNA sample

Sequence 16S genesSequence all genesCompare to databases of known 16S genes

Identify known species

Classify as new species

Compare to database of genes with known functions

WHO’S THERE?

WHAT ARE THEY DOING?

or

https://learn.genetics.utah.edu/content/microbiome/study/

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When do we get colonized?

Possibly before birth – diverse intracellular bacteria found in 27% of placentas in crossectional study suggesting maternal fetal1 Meconium from CS and vaginally delivered babies did not differ in bacterial composition – gut colonization occurs before delivery2

Bacteria also present in cord blood and amniotic fluid even in elected CSections

3

1.Kjersti A et

al(2014) 2.Martin

R et al (

2016) 3.

Bearfield

C et al(2002)

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Does it matter how we are born?

C-sectionVaginal birth

Colonised

by mother’s skin biome

Greater risk of obesity, allergy

Mother’s vaginal and gut biome

Less risk of obesity, allergy

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What happens after birth?

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Gut microbiome progression in early childhood

Developmental phase(3-14mo) Transitional phase(15-30mo)Stable phase(31-46mo)

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Temporal development of the gut

microbiome early childhood from the TEDDY study Christopher J. Stewart1,2,18

*

,

Nadim

J. Ajami

1,18

, Jacqueline L. O’Brien1, Diane S. Hutchinson1

, Daniel P. Smith

1

, Matthew C. Wong

1

, Matthew C. ross

1

,

richard

e. Lloyd

1

,

HarshaVardhan

Doddapaneni

3

, Ginger A. Metcalf

3

, Donna Muzny

3

,

richard

A. Gibbs

3

,

tommi

Vatanen

4

, Curtis Huttenhower

4

,

ramnik

J. Xavier

4

, Marian rewers

5

, William Hagopian

6

,

Jorma

toppari

7,8

,

Anette

-G. Ziegler

9,10,11

, Jin-

Xiong

She

12

,

Beena

Akolkar

13

,

Ake

Lernmark

14

,

Heikki

Hyoty

15,16

, Kendra Vehik

17

, Jeffrey P. Krischer

17

& Joseph F. Petrosino

1

*

TEDDY –

The

E

nvironmental

D

eterminants of Diabetes in the Young

903 children Europe and US

12500 stool samples

Aged 3-46

mo

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Conclusions from TEDDY study

With increasing age,the bacterial diversity of the microbiome expandedBifidobacterium predominated the developmental stage and was higher in breastfed infants.The Firmicutes dominated the third stage and were noted to increase with the introduction of solidsVaginally born infants had higher levels of Bacteroides and a higher diversity overall

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Thank you