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Oxford Inflammatory Bowel Disease & Hepatology MasterClass The microbiota of gut and liver disease Philippe Seksik Hôpital Saint-Antoine, APHP MMBPI ERL U1057 / UMR7203

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Page 1: The microbiota of gut and liver disease - University of Oxford · 100 95 90 S1 S2 S5 S4 S3 % similarity Stability over 2 years The dominant human faecal microbiota is stable Relative

Oxford Inflammatory Bowel Disease & Hepatology MasterClass

The microbiota of gut and liver disease

Philippe Seksik

Hôpital Saint-Antoine, APHP MMBPI ERL U1057 / UMR7203

Page 2: The microbiota of gut and liver disease - University of Oxford · 100 95 90 S1 S2 S5 S4 S3 % similarity Stability over 2 years The dominant human faecal microbiota is stable Relative

Philippe SEKSIK

ABBOTT

BIOCODEX

FERRING

MSD

Disclosures

Page 3: The microbiota of gut and liver disease - University of Oxford · 100 95 90 S1 S2 S5 S4 S3 % similarity Stability over 2 years The dominant human faecal microbiota is stable Relative

Gut microbiota

Page 4: The microbiota of gut and liver disease - University of Oxford · 100 95 90 S1 S2 S5 S4 S3 % similarity Stability over 2 years The dominant human faecal microbiota is stable Relative

Gut microbiota

Page 5: The microbiota of gut and liver disease - University of Oxford · 100 95 90 S1 S2 S5 S4 S3 % similarity Stability over 2 years The dominant human faecal microbiota is stable Relative

Beginning to see the light

Page 6: The microbiota of gut and liver disease - University of Oxford · 100 95 90 S1 S2 S5 S4 S3 % similarity Stability over 2 years The dominant human faecal microbiota is stable Relative

Why do we know so little ?

What do we know ? For gut & liver diseases

In the future ?

The gut microbiota

Page 7: The microbiota of gut and liver disease - University of Oxford · 100 95 90 S1 S2 S5 S4 S3 % similarity Stability over 2 years The dominant human faecal microbiota is stable Relative

Oxford Inflammatory Bowel Disease & Hepatology MasterClass

3 difficulties in studying the microbiota

Page 8: The microbiota of gut and liver disease - University of Oxford · 100 95 90 S1 S2 S5 S4 S3 % similarity Stability over 2 years The dominant human faecal microbiota is stable Relative

MICROBIOTA

All the micro-organisms within the gut

Bacteria

Page 9: The microbiota of gut and liver disease - University of Oxford · 100 95 90 S1 S2 S5 S4 S3 % similarity Stability over 2 years The dominant human faecal microbiota is stable Relative

MICROBIOTA

All the micro-organisms within the gut

Bacteria

Virus

Page 10: The microbiota of gut and liver disease - University of Oxford · 100 95 90 S1 S2 S5 S4 S3 % similarity Stability over 2 years The dominant human faecal microbiota is stable Relative

MICROBIOTA

All the micro-organisms within the gut

Bacteria

Virus (Phages)

Page 11: The microbiota of gut and liver disease - University of Oxford · 100 95 90 S1 S2 S5 S4 S3 % similarity Stability over 2 years The dominant human faecal microbiota is stable Relative

MICROBIOTA

All the micro-organisms within the gut

Bacteria

Virus (Phages)

Page 12: The microbiota of gut and liver disease - University of Oxford · 100 95 90 S1 S2 S5 S4 S3 % similarity Stability over 2 years The dominant human faecal microbiota is stable Relative

MICROBIOTA

All the micro-organisms within the gut

Bacteria

Virus (Phages)

Fungi

http://images.google.de/imgres?imgurl=http://www.ecplanet.com/pic/2004/09/1096090164/saccharomyces.jpg&imgrefurl=http://www.ecplanet.com/canale/scienza-1/ricerche-21/1/0/14350/it/ecplanet.rxdf&h=200&w=200&sz=6&tbnid=zuCuS9VRZnoJ:&tbnh=99&tbnw=99&hl=de&start=7&
Page 13: The microbiota of gut and liver disease - University of Oxford · 100 95 90 S1 S2 S5 S4 S3 % similarity Stability over 2 years The dominant human faecal microbiota is stable Relative

MICROBIOTA

All the micro-organisms within the gut

Bacteria

Virus (Phages)

Fungi

Archaea

http://images.google.de/imgres?imgurl=http://www.ecplanet.com/pic/2004/09/1096090164/saccharomyces.jpg&imgrefurl=http://www.ecplanet.com/canale/scienza-1/ricerche-21/1/0/14350/it/ecplanet.rxdf&h=200&w=200&sz=6&tbnid=zuCuS9VRZnoJ:&tbnh=99&tbnw=99&hl=de&start=7&
Page 14: The microbiota of gut and liver disease - University of Oxford · 100 95 90 S1 S2 S5 S4 S3 % similarity Stability over 2 years The dominant human faecal microbiota is stable Relative

3 difficulties in studying the microbiota

Bacteria

Virus (Phages)

Fungi

Archaea

First difficulty =

EXTREME CULTURE CONDITIONS

http://images.google.de/imgres?imgurl=http://www.ecplanet.com/pic/2004/09/1096090164/saccharomyces.jpg&imgrefurl=http://www.ecplanet.com/canale/scienza-1/ricerche-21/1/0/14350/it/ecplanet.rxdf&h=200&w=200&sz=6&tbnid=zuCuS9VRZnoJ:&tbnh=99&tbnw=99&hl=de&start=7&
Page 15: The microbiota of gut and liver disease - University of Oxford · 100 95 90 S1 S2 S5 S4 S3 % similarity Stability over 2 years The dominant human faecal microbiota is stable Relative

Cultivable fraction

20% of gut microbiota

Page 16: The microbiota of gut and liver disease - University of Oxford · 100 95 90 S1 S2 S5 S4 S3 % similarity Stability over 2 years The dominant human faecal microbiota is stable Relative

Culture independent methods

Cultivable fraction

20% of gut microbiota

Page 17: The microbiota of gut and liver disease - University of Oxford · 100 95 90 S1 S2 S5 S4 S3 % similarity Stability over 2 years The dominant human faecal microbiota is stable Relative

3 difficulties in studying the microbiota

Second difficulty = LARGE NUMBERS

Page 18: The microbiota of gut and liver disease - University of Oxford · 100 95 90 S1 S2 S5 S4 S3 % similarity Stability over 2 years The dominant human faecal microbiota is stable Relative

Bacterial populations

Abundance : 1014 bacteria

Diversity : ~ 1000 species

Page 19: The microbiota of gut and liver disease - University of Oxford · 100 95 90 S1 S2 S5 S4 S3 % similarity Stability over 2 years The dominant human faecal microbiota is stable Relative

Viral populations

Viral genome = 336Mb vast majority = phages or unknown

Minot S, et al Genome Res. 2011

Page 20: The microbiota of gut and liver disease - University of Oxford · 100 95 90 S1 S2 S5 S4 S3 % similarity Stability over 2 years The dominant human faecal microbiota is stable Relative

3 difficulties in studying the microbiota

Third difficulty = COMPLEXITY Ecosystem

Page 21: The microbiota of gut and liver disease - University of Oxford · 100 95 90 S1 S2 S5 S4 S3 % similarity Stability over 2 years The dominant human faecal microbiota is stable Relative

Bacteria

IgA

Milieu

Virus

Page 22: The microbiota of gut and liver disease - University of Oxford · 100 95 90 S1 S2 S5 S4 S3 % similarity Stability over 2 years The dominant human faecal microbiota is stable Relative

Bacteria

IgA

Milieu

Virus Bacteriocins Quorum sensing

Page 23: The microbiota of gut and liver disease - University of Oxford · 100 95 90 S1 S2 S5 S4 S3 % similarity Stability over 2 years The dominant human faecal microbiota is stable Relative

Bacteria

IgA

Nutriments Milieu

Virus Bile Acids

Xenobiotic

Bacteriocins Quorum sensing

Page 24: The microbiota of gut and liver disease - University of Oxford · 100 95 90 S1 S2 S5 S4 S3 % similarity Stability over 2 years The dominant human faecal microbiota is stable Relative

Bacteria

IgA

Milieu

Virus Bacteriocins Quorum sensing

Nutriments

Xenobiotic

Bile Acids

Page 25: The microbiota of gut and liver disease - University of Oxford · 100 95 90 S1 S2 S5 S4 S3 % similarity Stability over 2 years The dominant human faecal microbiota is stable Relative

Bacteria

sIgA

Epithelium

IgA

tight junctions

specialized cells Paneth, M

Milieu

Mucus

Virus

anti-microbial Peptides

Bacteriocins Quorum sensing

Nutriments

Xenobiotic

Bile Acids

Page 26: The microbiota of gut and liver disease - University of Oxford · 100 95 90 S1 S2 S5 S4 S3 % similarity Stability over 2 years The dominant human faecal microbiota is stable Relative

Bacteria

sIgA

Epithelium

IgA

tight junctions

specialized cells Paneth, M

Milieu

Mucus

Virus

anti-microbial Peptides

Bacteriocins Quorum sensing

Nutriments

Xenobiotic

Bile Acids

Page 27: The microbiota of gut and liver disease - University of Oxford · 100 95 90 S1 S2 S5 S4 S3 % similarity Stability over 2 years The dominant human faecal microbiota is stable Relative

What do we know ?

1. Implementation composition

2. Stability - change / resilience

3. Functions

3 major findings

Page 28: The microbiota of gut and liver disease - University of Oxford · 100 95 90 S1 S2 S5 S4 S3 % similarity Stability over 2 years The dominant human faecal microbiota is stable Relative

What do we know ?

1. Implementation composition

2. Stability - Change / Resilience

3. functions

Implementation composition

Page 29: The microbiota of gut and liver disease - University of Oxford · 100 95 90 S1 S2 S5 S4 S3 % similarity Stability over 2 years The dominant human faecal microbiota is stable Relative

Birth: sterile digestive tract

Acquisition of an "adult" microbiota (2-6 years)

Bacterial colonisation

Page 30: The microbiota of gut and liver disease - University of Oxford · 100 95 90 S1 S2 S5 S4 S3 % similarity Stability over 2 years The dominant human faecal microbiota is stable Relative

Birth: sterile digestive tract

Acquisition of an "adult" microbiota (2-6 years)

Bacterial colonisation

Environment &

host factors

Fallani et al. JPGN 2010

Page 31: The microbiota of gut and liver disease - University of Oxford · 100 95 90 S1 S2 S5 S4 S3 % similarity Stability over 2 years The dominant human faecal microbiota is stable Relative

Host factors

Rawls et al., Cell 2006

Page 32: The microbiota of gut and liver disease - University of Oxford · 100 95 90 S1 S2 S5 S4 S3 % similarity Stability over 2 years The dominant human faecal microbiota is stable Relative

Reciprocal gut microbiota transplants

Host factors

Rawls et al., Cell 2006

Page 33: The microbiota of gut and liver disease - University of Oxford · 100 95 90 S1 S2 S5 S4 S3 % similarity Stability over 2 years The dominant human faecal microbiota is stable Relative

Reciprocal gut microbiota transplants

Microbiota composition under the control of

genetic determinants

Rawls et al., Cell 2006

Reciprocal gut microbiota transplants

Page 34: The microbiota of gut and liver disease - University of Oxford · 100 95 90 S1 S2 S5 S4 S3 % similarity Stability over 2 years The dominant human faecal microbiota is stable Relative

Microbiota composition under the control of

genetic determinants

Stewart et al., J. Med. Microbiol. 2005; Zoetendal et al., Microb. Ecol. Health Dis. 2001; Turnbaugh PJ et al .PNAS 2010

Page 35: The microbiota of gut and liver disease - University of Oxford · 100 95 90 S1 S2 S5 S4 S3 % similarity Stability over 2 years The dominant human faecal microbiota is stable Relative

Bacterial populations

Actinobacteria Bacteroidetes

Firmicutes

Three major phyla

Li et al 2008 (n = 5, ~7000 seq) Eckburg et al 2006 (n = 3, ~2500 seq) Manichanh et al 2006 (n = 6, ~500 seq) Gill et al 2006 (n = 2, ~2000 seq)

Page 36: The microbiota of gut and liver disease - University of Oxford · 100 95 90 S1 S2 S5 S4 S3 % similarity Stability over 2 years The dominant human faecal microbiota is stable Relative

What do we know ?

1. Implementation composition

2. Stability - change / resilience

3. functions

Stability - change / resilience

Page 37: The microbiota of gut and liver disease - University of Oxford · 100 95 90 S1 S2 S5 S4 S3 % similarity Stability over 2 years The dominant human faecal microbiota is stable Relative

Microbiota profile

Unique to each individual

«Bar Code»

Page 38: The microbiota of gut and liver disease - University of Oxford · 100 95 90 S1 S2 S5 S4 S3 % similarity Stability over 2 years The dominant human faecal microbiota is stable Relative

Inter individual variability

Species diversity profiling of the dominant fecal microbiota of adults

Zoetendahl et al. 1998 Seksik et al. 2003 Vanhoutte et al. 2004

The faecal microbiota of adults is specific of individuals

14 healthy adults

Page 39: The microbiota of gut and liver disease - University of Oxford · 100 95 90 S1 S2 S5 S4 S3 % similarity Stability over 2 years The dominant human faecal microbiota is stable Relative

10

0

95

90

S1

S2

S5

S4

S3

% similarity

Stability over 2 years

The dominant human faecal microbiota is stable

Relative stability in a same individual

Seksik et al. Gut 2003

Profiles in a same individual

Species diversity profiling of the dominant fecal microbiota of adults

Zoetendahl et al. 1998 Seksik et al. 2003 Vanhoutte et al. 2004

The faecal microbiota of adults is specific of individuals

14 healthy adults

Page 40: The microbiota of gut and liver disease - University of Oxford · 100 95 90 S1 S2 S5 S4 S3 % similarity Stability over 2 years The dominant human faecal microbiota is stable Relative

Stability - change / resilience

Food

Antibiotics

Intestinal Infection

IBD flare

Others

Page 41: The microbiota of gut and liver disease - University of Oxford · 100 95 90 S1 S2 S5 S4 S3 % similarity Stability over 2 years The dominant human faecal microbiota is stable Relative

Ley et al, science 2008

Food intake determines biodiversity

Page 42: The microbiota of gut and liver disease - University of Oxford · 100 95 90 S1 S2 S5 S4 S3 % similarity Stability over 2 years The dominant human faecal microbiota is stable Relative

Community structure of faecal microbiota according to diet (cattle)

Diet determines composition

Shanks et al.AEM 2011

Page 43: The microbiota of gut and liver disease - University of Oxford · 100 95 90 S1 S2 S5 S4 S3 % similarity Stability over 2 years The dominant human faecal microbiota is stable Relative

40

50

60

70

80

90

100

110

0 1 2 3 4 …. 30 …. 60

Time (days)

sim

ila

rit

y %

***

Dominant human faecal microbiota upon short-course antibiotic challenge (De la Cochetiere et al. JCM 2005)

Erythromycin 500mg/d 4 days

Antibiotics: an ecological disaster

Page 44: The microbiota of gut and liver disease - University of Oxford · 100 95 90 S1 S2 S5 S4 S3 % similarity Stability over 2 years The dominant human faecal microbiota is stable Relative

40

50

60

70

80

90

100

110

0 1 2 3 4 …. 30 …. 60

Time (days)

sim

ila

rit

y %

***

Resilience of the microbiota

Erythromycin 500mg/d 4 days

Dominant human faecal microbiota upon short-course antibiotic challenge (De la Cochetiere et al. JCM 2005)

Page 45: The microbiota of gut and liver disease - University of Oxford · 100 95 90 S1 S2 S5 S4 S3 % similarity Stability over 2 years The dominant human faecal microbiota is stable Relative

What do we know ?

1. Implementation composition

2. Stability - Change / Resilience

3. Functions

Functions

Page 46: The microbiota of gut and liver disease - University of Oxford · 100 95 90 S1 S2 S5 S4 S3 % similarity Stability over 2 years The dominant human faecal microbiota is stable Relative

2 major functions

Metabolic functions

Immune / protection

Page 47: The microbiota of gut and liver disease - University of Oxford · 100 95 90 S1 S2 S5 S4 S3 % similarity Stability over 2 years The dominant human faecal microbiota is stable Relative

Metabolic functions

Degradation of sugars, proteins

Control fat storage

Page 48: The microbiota of gut and liver disease - University of Oxford · 100 95 90 S1 S2 S5 S4 S3 % similarity Stability over 2 years The dominant human faecal microbiota is stable Relative

Backhed et al., PNAS 2004

bacteria

Substrate

Epithelial cells

Page 49: The microbiota of gut and liver disease - University of Oxford · 100 95 90 S1 S2 S5 S4 S3 % similarity Stability over 2 years The dominant human faecal microbiota is stable Relative

Backhed et al., PNAS 2004

Inhibition of fiaf

bacteria

Substrate

Epithelial cells

Selective repression of fiaf expression in the intestine

Page 50: The microbiota of gut and liver disease - University of Oxford · 100 95 90 S1 S2 S5 S4 S3 % similarity Stability over 2 years The dominant human faecal microbiota is stable Relative

Backhed et al., PNAS 2004

Inhibition of fiaf

Activation of the LPL Energy recovery from food

bacteria

Substrate

Epithelial cells

Selective repression of fiaf expression in the intestine

Page 51: The microbiota of gut and liver disease - University of Oxford · 100 95 90 S1 S2 S5 S4 S3 % similarity Stability over 2 years The dominant human faecal microbiota is stable Relative

Inhibition of fiaf

Activation of the LPL Energy recovery from food

energy balance

inputs

outputs

Better recovery of energy from food

Reduced use of energy reserves

bacteria

Substrate

Epithelial cells

Selective repression of fiaf expression in the intestine

Backhed et al., PNAS 2004

Page 52: The microbiota of gut and liver disease - University of Oxford · 100 95 90 S1 S2 S5 S4 S3 % similarity Stability over 2 years The dominant human faecal microbiota is stable Relative

Changes in the intestinal microbiota in obese

Metabolic functions

Degradation of sugars, proteins

Control fat storage

Page 53: The microbiota of gut and liver disease - University of Oxford · 100 95 90 S1 S2 S5 S4 S3 % similarity Stability over 2 years The dominant human faecal microbiota is stable Relative

Imbalance in microbiota composition

Dysbiosis

Page 54: The microbiota of gut and liver disease - University of Oxford · 100 95 90 S1 S2 S5 S4 S3 % similarity Stability over 2 years The dominant human faecal microbiota is stable Relative

Firmicutes /Bacteroidetes ratio in obese mice and lean mice

Souris ob/ob : mutation sur le gène de la leptine

Relative increase in the Firmicutes at the expense of Bacteroidetes

Actinobacteria Bacteroidetes

Firmicutes

Microbiota in obese

→Dysbiosis

Ley et al., PNAS 2005

Page 55: The microbiota of gut and liver disease - University of Oxford · 100 95 90 S1 S2 S5 S4 S3 % similarity Stability over 2 years The dominant human faecal microbiota is stable Relative

Gut microbiota drives the phenotype

Dysbiosis

ob/ob

Page 56: The microbiota of gut and liver disease - University of Oxford · 100 95 90 S1 S2 S5 S4 S3 % similarity Stability over 2 years The dominant human faecal microbiota is stable Relative

Gut microbiota drives the phenotype

Dysbiosis

ob/ob

Wild type

Transfer microbiota

Page 57: The microbiota of gut and liver disease - University of Oxford · 100 95 90 S1 S2 S5 S4 S3 % similarity Stability over 2 years The dominant human faecal microbiota is stable Relative

Obese phenotype

Dysbiosis

ob/ob

Transfer microbiota

Wild type

Wild type

Gut microbiota drives the phenotype

Page 58: The microbiota of gut and liver disease - University of Oxford · 100 95 90 S1 S2 S5 S4 S3 % similarity Stability over 2 years The dominant human faecal microbiota is stable Relative

Example: TLR5 KO mice

Develop a 'metabolic syndrom'

Vigay-Kumar et al. Science 2010

Page 59: The microbiota of gut and liver disease - University of Oxford · 100 95 90 S1 S2 S5 S4 S3 % similarity Stability over 2 years The dominant human faecal microbiota is stable Relative

Dysbiosis

TLR 5 KO

Gut microbiota drives the phenotype

Page 60: The microbiota of gut and liver disease - University of Oxford · 100 95 90 S1 S2 S5 S4 S3 % similarity Stability over 2 years The dominant human faecal microbiota is stable Relative

Dysbiosis

TLR 5 KO

Transfer microbiota

Wild type

Gut microbiota drives the phenotype

Page 61: The microbiota of gut and liver disease - University of Oxford · 100 95 90 S1 S2 S5 S4 S3 % similarity Stability over 2 years The dominant human faecal microbiota is stable Relative

Dysbiosis

TLR 5 KO

Transfer microbiota

Wild type

Gut microbiota drives the phenotype

Metabolic syndrome in wild type mice

Page 62: The microbiota of gut and liver disease - University of Oxford · 100 95 90 S1 S2 S5 S4 S3 % similarity Stability over 2 years The dominant human faecal microbiota is stable Relative

Metabolic functions

Steatosis and dysmetabolic steato-hepatitis

Alcoholic hepatitis

Cirrhosis (carcinoma)

Page 63: The microbiota of gut and liver disease - University of Oxford · 100 95 90 S1 S2 S5 S4 S3 % similarity Stability over 2 years The dominant human faecal microbiota is stable Relative

IgA plasma cells (repertoire)

Shaping immune response

Anti-microbial peptides

Epithelial proliferation (carcinogenesis)

Immunes / protection functions

Lindner et al. J exp med. 2012

Page 64: The microbiota of gut and liver disease - University of Oxford · 100 95 90 S1 S2 S5 S4 S3 % similarity Stability over 2 years The dominant human faecal microbiota is stable Relative

In mice

Segmeted Filamentous Bacteria induit response Th17

Gaboriaud-Routhiau et al. Immunity 2009 Ivanov et al. Cell 2009

Atarashi et al. Science 2011

Shaping immune response

Clostridia : accumulation de Treg (Foxp3+) colon

Page 65: The microbiota of gut and liver disease - University of Oxford · 100 95 90 S1 S2 S5 S4 S3 % similarity Stability over 2 years The dominant human faecal microbiota is stable Relative

In mice

Segmeted Filamentous Bacteria induit response Th17

Gaboriaud-Routhiau et al. Immunity 2009 Ivanov et al. Cell 2009

Atarashi et al. Science 2011

Round et al. Science 2011

Shaping immune response

Clostridia : accumulation de Treg (Foxp3+) colon

Bacteroides fragilis (PSA) oriente IL10 Treg

Page 66: The microbiota of gut and liver disease - University of Oxford · 100 95 90 S1 S2 S5 S4 S3 % similarity Stability over 2 years The dominant human faecal microbiota is stable Relative

In mice

Feacalibacterium prausnitzii Sokol et al. PNAS 2008

Anti-inflammatory effect Induction of IL-10

Shaping immune response

Page 67: The microbiota of gut and liver disease - University of Oxford · 100 95 90 S1 S2 S5 S4 S3 % similarity Stability over 2 years The dominant human faecal microbiota is stable Relative

In mice

Feacalibacterium prausnitzii Sokol et al. PNAS 2008

Anti-inflammatory effect Induction of IL-10

Shaping immune response

Page 68: The microbiota of gut and liver disease - University of Oxford · 100 95 90 S1 S2 S5 S4 S3 % similarity Stability over 2 years The dominant human faecal microbiota is stable Relative

Dysbiosis in IBD

R2Ycum=0,719

- 3

- 2

- 1

0

1

2

3

- 6 - 5 - 4 - 3 - 2 - 1 0 1 2 3 4 5 6

t[2]=

0,0

85

t[1]=0,635

R2Ycum=0,772

- 4

- 3

- 2

- 1

0

1

2

3

4

- 5 - 4 - 3 - 2 - 1 0 1 2 3 4 5

t[2]=

0,0

79

t[1]=0,692

IBD in flare

Healthy subjects

IBD in remission

principal component analysis

Page 69: The microbiota of gut and liver disease - University of Oxford · 100 95 90 S1 S2 S5 S4 S3 % similarity Stability over 2 years The dominant human faecal microbiota is stable Relative

6.0 3.6 2.4 1.2 1.3

0%

20%

40%

60%

80%

100%

Healthy IBD in remission IBD in flare

Bacteroidetes

Firmicutes

6.0 3.6 2.4 1.2 1.3

Dysbiosis in IBD

Firmicutes / Bacteroidetes

Sokol et al. IBD 2009

Page 70: The microbiota of gut and liver disease - University of Oxford · 100 95 90 S1 S2 S5 S4 S3 % similarity Stability over 2 years The dominant human faecal microbiota is stable Relative

Lo

g10 C

FU

/g

*

*

7,00

7,50

8,00

8,50

9,00

9,50

10,00

10,50

11,00

11,50

12,00

Bacteria Bacteroides Firmicutes F. prausnitzii

Flare IBD (n= 35)

IBD in remission (n= 14)

Healthy (n=27)

Sokol et al. IBD 2009

Dysbiosis in IBD

Page 71: The microbiota of gut and liver disease - University of Oxford · 100 95 90 S1 S2 S5 S4 S3 % similarity Stability over 2 years The dominant human faecal microbiota is stable Relative

Chronic inflammation

Metabolic activities

SCFA

bile acids

Bacterial toxin (B fragilis)

Wu et al. Nat Med 2009

Goodwin et al PNAS 2011

Epithelial proliferation (carcinogenesis)

Ou et al. Nutr Cancer 2012

Page 72: The microbiota of gut and liver disease - University of Oxford · 100 95 90 S1 S2 S5 S4 S3 % similarity Stability over 2 years The dominant human faecal microbiota is stable Relative

Dysbiosis in colo-rectal cancer

Sobhani et al. Plos One 2011

Page 73: The microbiota of gut and liver disease - University of Oxford · 100 95 90 S1 S2 S5 S4 S3 % similarity Stability over 2 years The dominant human faecal microbiota is stable Relative

Immune / protection functions

IBD

Colo-rectal cancer

IBS

Infectious-colitis / antibiotic-associated

Intestinal ‘Allergy’ – Celiac disease

Page 74: The microbiota of gut and liver disease - University of Oxford · 100 95 90 S1 S2 S5 S4 S3 % similarity Stability over 2 years The dominant human faecal microbiota is stable Relative

Oxford Inflammatory Bowel Disease & Hepatology MasterClass

The Future

Page 75: The microbiota of gut and liver disease - University of Oxford · 100 95 90 S1 S2 S5 S4 S3 % similarity Stability over 2 years The dominant human faecal microbiota is stable Relative

Human gut microbiota

Abundance : 1014 bacteria

Diversity : ~ 1000 species

Our other genome

Page 76: The microbiota of gut and liver disease - University of Oxford · 100 95 90 S1 S2 S5 S4 S3 % similarity Stability over 2 years The dominant human faecal microbiota is stable Relative

Human gut microbiota

Sum of all bacterial DNAs = Metagenome

Abundance : 1014 bacteria

Diversity : ~ 1000 species

Our other genome

Page 77: The microbiota of gut and liver disease - University of Oxford · 100 95 90 S1 S2 S5 S4 S3 % similarity Stability over 2 years The dominant human faecal microbiota is stable Relative

Human gut microbiota

Metagenome (bacterial DNA): ~108 genes

100 to 150 x the human genome

Sum of all bacterial DNAs = Metagenome

Abundance : 1014 bacteria

Diversity : ~ 1000 species

Our other genome

Page 78: The microbiota of gut and liver disease - University of Oxford · 100 95 90 S1 S2 S5 S4 S3 % similarity Stability over 2 years The dominant human faecal microbiota is stable Relative

‘Metagenomic’ projects

Mullard A. The inside story, Nature 2008

Page 79: The microbiota of gut and liver disease - University of Oxford · 100 95 90 S1 S2 S5 S4 S3 % similarity Stability over 2 years The dominant human faecal microbiota is stable Relative

Description of a bacterial functional core

Turnbaugh et al., Nature 2008; MetaHIT Project ; Qin et al , Nature 2010

Page 80: The microbiota of gut and liver disease - University of Oxford · 100 95 90 S1 S2 S5 S4 S3 % similarity Stability over 2 years The dominant human faecal microbiota is stable Relative

Functional core

Description of a bacterial functional core

Turnbaugh et al., Nature 2008; MetaHIT Project ; Qin et al , Nature 2010

Page 81: The microbiota of gut and liver disease - University of Oxford · 100 95 90 S1 S2 S5 S4 S3 % similarity Stability over 2 years The dominant human faecal microbiota is stable Relative

38% of the bacterial genes shared by >50% of individuals (9% shared by> 80%)

We are quite the same

Functional core

Description of a bacterial functional core

Turnbaugh et al., Nature 2008; MetaHIT Project ; Qin et al , Nature 2010

Page 82: The microbiota of gut and liver disease - University of Oxford · 100 95 90 S1 S2 S5 S4 S3 % similarity Stability over 2 years The dominant human faecal microbiota is stable Relative

38% of the bacterial genes shared by >50% of individuals (9% shared by> 80%)

We are quite the same

Rare Genes Genes shared by ≤ 20 % of individuals = 2.4 millions genes

But far from identical Functional core

Description of a bacterial functional core

Turnbaugh et al., Nature 2008; MetaHIT Project ; Qin et al , Nature 2010

Page 83: The microbiota of gut and liver disease - University of Oxford · 100 95 90 S1 S2 S5 S4 S3 % similarity Stability over 2 years The dominant human faecal microbiota is stable Relative

Dysbiosis: differential analysis of the metagenome

Healthy

UC

Crohn’s disease

MetaHIT Project ; Qin et al , Nature 2010

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Microbiota +

Integrative platform

Data from the ecosytem

Genetic / metagenomics

Clinical data

Immune responses

Ecosystem interplay

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Microbiota +

Integrative platform

Data from the ecosytem

Genetic / metagenomics

Clinical data

Immune responses

Ecosystem interplay

Bio-informatics

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Goals

Better understanding of human physiology

To achieve normobiosis

Find new bio-markers

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Summary

Gut microbiota = ‘real’ organ

Involved in physiology metabolism, inflammation, cancer

Involved in many gastro-intestinal and hepatic disorders and diseases

Maintaining biodiversity / balance

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INRA Jouy-en-Josas Joel Doré Philippe Langella Luis Bermudez Chantal Bridonneau

ERL U1057 Germain Trugnan Ginette Thomas Sylvie Rajca Laurent Beaugerie Joelle Masliah Harry Sokol Bénédicte Arnaud Jean-Pierre Grill Dominique Rainteau Henri Duboc Marie-Anne Maubert Lydie Humbert Elodie Quevrain Antonin Lamazière Jacques Cosnes

UMRS 7203 Solange Lavielle Gérard Chassaing Jean-Maurice Mallet Olivier Lequin Rodrigue Marquant Joelle Runfola

Philippe Marteau


Bacteriophage transfer during faecal microbiota ...gut.bmj.com/content/gutjnl/early/2017/05/24/gutjnl-2017-313952... · Bacteriophage transfer during faecal microbiota transplantation

Scientific frontiers in faecal microbiota transplantation ...Design Systematic search was performed, FMt literature was critically appraised and a 1-day round-table discussion was

FMT Capsule G3 Clinical Primer - Digestive Health · 2020-04-30 · treating severe or severe-complicated CDI by FMT review protocols in Fischer et al, “Faecal microbiota transplantation

faecal incontinence

Therapies to modulate the gut microbiota from a dysbiosis to a … · 2015-11-23 · Firmicutes and Bacteroidetes are the only dominant phyla BACTERIOTHERAPY Transplantation of faecal

Presentation: The Regulation of Faecal Microbiota ... · protections-regarding-use-fecal-microbiota-transplantation) As our understanding of the risk factors related to FMT increases,

Comparative assessment of human and farm animal …archimer.ifremer.fr/doc/00000/11071/11297.pdf · 2011-03-01 · Comparative assessment of human and farm animal faecal microbiota

Improving faecal health of our pets - Petfood Forum · 2019-08-15 · •Faecal health score similar to ... •Fecal microbiota similar to cellulose. The role of fibre in canine dilated

Rapid assessment of faecal egg count and faecal egg count

Guidelines The use of faecal microbiota transplant as ... · Clostridium difficile infection (CDI), but there is also an emerging evidence base regarding potential applications in

Bugs, Guts and SpA - ssrmsr2015.weebly.comssrmsr2015.weebly.com/uploads/1/5/0/2/15021412/13__dr_david_ong_guts_bugs_and_spa.pdfNUHS Faecal Microbiota Transplantation Program November

spiral.imperial.ac.uk...Confidential: For Review Only The use of faecal microbiota transplant as treatment for recurrent or refractory Clostridium difficile infection and other potential

Guidelines The use of faecal microbiota transplant as treatment … · 2020. 5. 23. · prepared FMT treatments should be considered suitable when preparing FMT for the treatment

Draft standards for faecal microbiota transplant (FMT) products  · Web view2019-11-15 · The purpose of this consultation paper is to outline the proposed standards for faecal

Funding Requests – South, Central and West - NHS …€¦ · Web viewAddition of policies related to laser therapy in pilonidal sinus, faecal microbiota transplants, balloon catheter

Faecal microbiota transplantation alters gut microbiota in ... · placebo-controlled pilot study. MeTHODS Trial design Patients were included in a 6-month randomised double-blind

RESHAPING FAECAL GUT MICROBIOTA COMPOSITION BY THE …dadun.unav.edu/bitstream/10171/38279/1/Etxeberria U et al-JNB-14-445.pdf · RESHAPING FAECAL GUT MICROBIOTA COMPOSITION BY THE

ORIGINAL ARTICLE Bacteriophage transfer during faecal … · ORIGINAL ARTICLE Bacteriophage transfer during faecal microbiota transplantation in Clostridium difficile infection is

Characterisation of the faecal metabolomeepubs.surrey.ac.uk/805947/9/Characterisation of the... · structure and metabolic function of normal gut microbiota and how this responds

Recurrent Clostridium difficile : The Role of Faecal Microbiota Transplants Dr Jonathan Sutton Ysbyty Gwynedd Betsi Cadwaladr University Health Board

THE SENSITIVITY OF DIRECT FAECAL EXAMINATION, FAECAL

Faecal Analysis

Pelletizing of faecal sludge. Processing of faecal … of faecal sludge. Processing of faecal sludge into fuel pellets. Faecal sludge management Worldwide, sanitation needs of 2.7

Faecal Microbiota Transplant in Inflammatory Bowel … · Oxford Inflammatory Bowel Disease MasterClass Faecal Microbiota Transplant in Inflammatory Bowel Disease Robert Bryant Translational

Faecal microbiota transplantation alters gut microbiota in ... · improvement in iBS. However, different study designs and larger studies are required to examine the role of FMt in

MÁSTER UNIVERSITARIO EN INVESTIGACIÓN EN CIENCIAS …€¦ · FACULTAD DE CIENCIAS ECONÓMICAS Y EMPRESARIALES HORARIO DEL CURSO 2016-2017 15-16 S5 S5 S5 S5 S5 S5 S5 S5 S5 S5 S5

ORIGINAL ARTICLE Anal gas evacuation and colonic ... · Microbiota analysis A total of 100 faecal samples (basal and challenge phases in each participant) were used for microbial

RESEARCH REPOSITORY · Clostridium difficile infection: evolution, phylogeny and molecular epidemiology ... There has been an increasing interest in faecal microbiota transplantation

Exploration of the faecal microbiota and biomarker

Effects of dietary fat on gut microbiota and faecal ... · 1/18/2019 · content alter the gut microbiota and faecal metabolomic profiles, and to determine their relationship with

Faecal culturable microbiota, growth and clinical

Clinical and immunologic effects of faecal microbiota ...€¦ · five consecutive mornings according to our standard procedure for C. difficile treatment. Since the first FMT did

University of Birmingham Systematic review with meta ... · 17 Clostridium difficile infection (CDI) is the commonest nosocomial cause of diarrhoea. Faecal 18 microbiota transplantation

Draft standards for faecal microbiota transplant (FMT ... · Draft Standards for Faecal microbiota transplant (FMT) products V1.0 November 2019 Page 4 of 69 Subsection 9 Blood (serum

Faecal Egg