Healthy guts exclude oxygen - Virology Education...
Transcript of Healthy guts exclude oxygen - Virology Education...
Healthy guts exclude oxygen
4th International Workshop on Microbiome in HIV Pathogenesis, Prevention and Treatment
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Control of microbes by our
immune systemFighting off
bad bugs
Balancing our
microbial self
Immune
system
What is gut homeostasis?
Gut microbiota of humans
What is a balanced microbial community?
Immune
system
Balancing our
microbial self
Microbial community structure in the intestine
Gut microbiota of humans Gut microbiota of mice
Obligate anaerobes(Bacteroidetes and
Firmicutes)
Fiber
Short-chain fatty
acids
Dysbiosis: shift from obligate to facultative anaerobes
Gut microbiota of humans Gut microbiota of mice
Obligate anaerobes(Bacteroidetes and
Firmicutes)
Dysbiosis
Facultative anaerobes(Proteobacteria)
Dysbiosis: shift from obligate to facultative anaerobes
Obligate anaerobes(Bacteroidetes and
Firmicutes)
Dysbiosis
Facultative anaerobes(Proteobacteria)
Lupp et al., 2007
Stecher et al., 2007
Barman et al., 2008
Chemically-induced colitis
Salmonella infection
Frank et al., 2007 Inflammatory
bowel disease
(IBD)
High-fat
diet
Necrotizing
enterocolitis
(NEC)Toxoplasma
infection
Genetically-induced colitis
Raetz et al., 2013
Molloy et al. 2013
Haag et al. 2012
Lupp et al., 2007
Garrett et al., 2010
Martinez-Medina
et al., 2014
Irritable
bowel syndrome
(IBS)
Colorectal cancer
Krogius-Kurikka et
al. 2009
Carroll et al., 2012
Arthur et al., 2012
Antibiotics
Bohnhoff et al., 1954
Saito, 1961
Mai et al., 2011
Normann et al., 2013
Citrobacter
infectionLupp et al., 2007
HIV
enteropathyMutlu et al., 2014
Dysbiosis: shift from obligate to facultative anaerobes
Obligate anaerobes(Bacteroidetes and
Firmicutes)
Dysbiosis
Facultative anaerobes(Proteobacteria)
Lupp et al., 2007
Stecher et al., 2007
Barman et al., 2008
Chemically-induced colitis
Salmonella infection
Frank et al., 2007 Inflammatory
bowel disease
(IBD)
High-fat
diet
Necrotizing
enterocolitis
(NEC)Toxoplasma
infection
Genetically-induced colitis
Raetz et al., 2013
Molloy et al. 2013
Haag et al. 2012
Lupp et al., 2007
Garrett et al., 2010
Martinez-Medina
et al., 2014
Irritable
bowel syndrome
(IBS)
Colorectal cancer
Krogius-Kurikka et
al. 2009
Carroll et al., 2012
Arthur et al., 2012
Antibiotics
Bohnhoff et al., 1954
Saito, 1961
Mai et al., 2011
Normann et al., 2013
Citrobacter
infectionLupp et al., 2007
Is there a common driver for gut dysbiosis?
HIV
enteropathyMutlu et al., 2014
Dysbiosis: shift from obligate to facultative anaerobes
Obligate anaerobes(Bacteroidetes and
Firmicutes)
Dysbiosis
Facultative anaerobes(Proteobacteria)
Salmonella infection
Is there a common driver for gut dysbiosis?
Chemically-induced colitis
Inflammatory
bowel disease
(IBD)
High-fat
diet
Necrotizing
enterocolitis
(NEC)Toxoplasma
infection
Genetically-induced colitis
Irritable
bowel syndrome
(IBS)
Colorectal cancer
Antibiotics
Citrobacter
infection
HIV
enteropathyMutlu et al., 2014
Crypt
Clostridia
Butyrate
Complex
carbohydrates
Undifferentiated
colonocyte
Mature
colonocyte
H2O
H2O
Blood vessel
O2
O2
CO2
Streptomycin102
103
104
105
106
107
108
109
1010
“co
lon
iza
tio
n
resis
tance”
Mock
treatment
E. coli Nissle 1917
CF
U/g
co
lon
co
nte
nt
Streptomycin
(single dose)
Antibiotics drive a luminal expansion of Enterobacteriaceae
Mariana
Byndloss
Crypt
Clostridia
Butyrate
Complex
carbohydrates
Undifferentiated
colonocyte
Mature
colonocyte
H2O
H2O
Blood vessel
O2
O2
CO2
1011
1012
1013
Day 3 after
strep
**
Eub
acte
ria
(16S
rR
NA
gene
cop
ies/
g co
lon
cont
ents
)
Strep: - +
Streptomycin102
103
104
105
106
107
108
109
1010
“co
lon
iza
tio
n
resis
tance”
Mock
treatment
E. coli Nissle 1917
CF
U/g
co
lon
co
nte
nt
Streptomycin
(single dose)
Antibiotics drive a luminal expansion of Enterobacteriaceae
2017 Science 357: 570
Mariana
Byndloss
Streptomycin
(single dose)
108
109
1010
1011
1012
Clo
str
idia
(16S
rR
NA
copi
es/g
col
on c
onte
nts)
Strep:
**
- +
Day 3 after
strep
0
20
40
60
80
100
Rel
ativ
e ab
unda
nce
of
Clo
strid
ia fa
mili
es (
%)
Strep: - +
Day 3 after
strep
Clostridiaceae
Peptostreptococcaceae
Veillonellaceae
Ruminococcaceae
LachnospiraceaeOther:
Butyrate producers:
1011
1012
1013
Day 3 after
strep
**
Eub
acte
ria
(16S
rR
NA
gene
cop
ies/
g co
lon
cont
ents
)
Strep: - +
Crypt
Undifferentiated
colonocyte
Mature
colonocyte
H2O
H2O
Blood vessel
O2
O2
CO2
Butyrate
Complex
carbohydrates
Clostridia
Antibiotics
X
Streptomycin depletes butyrate-producing Clostridia
2017 Science 357: 570
Mariana
Byndloss
108
109
1010
1011
1012
Clo
str
idia
(16S
rR
NA
copi
es/g
col
on c
onte
nts)
Strep:
**
- +
Day 3 after
strep
0
20
40
60
80
100
Rel
ativ
e ab
unda
nce
of
Clo
strid
ia fa
mili
es (
%)
Strep: - +
Day 3 after
strep
Clostridiaceae
Peptostreptococcaceae
Veillonellaceae
Ruminococcaceae
LachnospiraceaeOther:
Butyrate producers:
Crypt
Undifferentiated
colonocyte
Mature
colonocyte
H2O
H2O
Blood vessel
O2
O2
CO2
Butyrate
Complex
carbohydrates
Clostridia
Antibiotics
X
X
Streptomycin lowers butyrate levels
Cec
albu
tyra
te (μm
ol/g
)
Strep:
0.01
0.1
10
1
**
- +
Day 3 after
strep
2017 Science 357: 570
Mariana
Byndloss
108
109
1010
1011
1012
Clo
str
idia
(16S
rR
NA
copi
es/g
col
on c
onte
nts)
Strep:
**
- +
Day 3 after
strep
0
20
40
60
80
100
Rel
ativ
e ab
unda
nce
of
Clo
strid
ia fa
mili
es (
%)
Strep: - +
Day 3 after
strep
Clostridiaceae
Peptostreptococcaceae
Veillonellaceae
Ruminococcaceae
LachnospiraceaeOther:
Butyrate producers:
Crypt
Undifferentiated
colonocyte
Mature
colonocyte
H2O
H2O
Blood vessel
O2
O2
CO2
Butyrate
Complex
carbohydrates
Clostridia
Antibiotics
X
X
Streptomycin lowers butyrate levels
Cec
albu
tyra
te (μm
ol/g
)
Strep:
0.01
0.1
10
1
**
- +
Day 3 after
strep
O2
O2
CO2
Butyrate
Butyrate
ATPADP
Na+
Na+
Na+
Crypt
Undifferentiated
colonocyte
Mature
colonocyte
H2O
H2O
Blood vessel
O2
O2
CO2
Butyrate
Complex
carbohydrates
Clostridia
Antibiotics
X
X
Streptomycin lowers butyrate levels
O2
O2
CO2
Butyrate
Butyrate
ATPADP
Na+
Na+
Na+
Mock-treated
Lumen Mucosa
Hypoxia
(< 1% oxygen)
10%
1%
0.1%
O2
grad
ient
Fabian Rivera-Chavez
2016 CH&M 19:443
Crypt
Blood vessel
10%
1%
0.1%
O2
grad
ient
O2
O2
Butyrate
Complex
carbohydrates
Clostridia
O2
H2O
H2O
X
X
Antibiotics
Mock-treated
Lumen Mucosa
Strep-treated
LumenMucosa
Hypoxia
(< 1% oxygen)
Streptomycin increases epithelial oxygenation
O2
O2
O2
Glucose
Glucose
Lactate
ATP
ADP
Fabian Rivera-Chavez
2016 CH&M 19:443
Crypt
Blood vessel
10%
1%
0.1%
O2
grad
ient
O2
O2
Butyrate
Complex
carbohydrates
Clostridia
O2
H2O
H2O
X
X
Antibiotics
Mock-treated
Lumen Mucosa
Lumen
Mucosa
Strep-treated +
tributyrinStrep-treated
LumenMucosa
Hypoxia
(< 1% oxygen)
Crypt
Undifferentiated
colonocyte
Mature
colonocyte
H2O
H2O
Blood vessel
O2
O2
CO2
Butyrate
Complex
carbohydrates
Clostridia
Antibiotics
XTributyrin
Streptomycin increases epithelial oxygenation
10%
1%
0.1%
O2
grad
ient
2016 CH&M 19:443
Crypt
Blood vessel
10%
1%
0.1%
O2
grad
ient
O2
O2
Butyrate
Complex
carbohydrates
Clostridia
O2
H2O
H2O
X
X
Antibiotics Oxygen drives an expansion of Escherichia coli
2017 Science 357: 570
cydA cydB Cytochrome bd oxidase
(microaerobic conditions)
E. coli
Nissle 1917
cydAB
mutant
E. coli
?
Crypt
Blood vessel
10%
1%
0.1%
O2
grad
ient
O2
O2
Butyrate
Complex
carbohydrates
Clostridia
O2
H2O
H2O
X
X
Antibiotics Oxygen drives an expansion of Escherichia coli
Strep: - +
CI i
n co
lon
cont
ents
(E. c
oli w
tvs.
cyd
AB
)
0
2
4
6
8
10
12
2017 Science 357: 570
cydA cydB Cytochrome bd oxidase
(microaerobic conditions)
E. coli
Nissle 1917
cydAB
mutant
E. coli
cydAB
Crypt
Blood vessel
10%
1%
0.1%
O2
grad
ient
O2
O2
Butyrate
Complex
carbohydrates
Clostridia
O2
H2O
H2O
X
X
Antibiotics
Crypt
Undifferentiated
colonocyte
Mature
colonocyte
H2O
H2O
Blood vessel
O2
O2
CO2
Butyrate
Complex
carbohydrates
Clostridia
Antibiotics
XTributyrin
10%
1%
0.1%
O2
grad
ient
2017 Science 357: 570
Strep:Tributyrin:
--
+-
++
CI i
n co
lon
cont
ents
(E. c
oli w
tvs.
cyd
AB
)
0
2
4
6
8
10
12
cydA cydB Cytochrome bd oxidase
(microaerobic conditions)
E. coli
Nissle 1917
cydAB
mutant
Oxygen drives an expansion of Escherichia coli
Crypt
Blood vessel
10%
1%
0.1%
O2
grad
ient
O2
O2
Butyrate
Complex
carbohydrates
Clostridia
O2
H2O
H2O
X
X
Antibiotics
Crypt
Undifferentiated
colonocyte
Mature
colonocyte
H2O
H2O
Blood vessel
O2
O2
CO2
Butyrate
Complex
carbohydrates
Clostridia
Antibiotics
Tributyrin
10%
1%
0.1%
O2
grad
ient
2017 Science 357: 570
Strep:Tributyrin:
C17:
---
+--
++-
+-+
CI i
n co
lon
cont
ents
(E. c
oli w
tvs.
cyd
AB
)
0
2
4
6
8
10
12
cydA cydB Cytochrome bd oxidase
(microaerobic conditions)
E. coli
Nissle 1917
cydAB
mutant
Oxygen drives an expansion of Escherichia coliC17
Dysbiosis Salmonella infectionChemically-induced colitis
Inflammatory
bowel disease
(IBD)
High-fat
diet
Necrotizing
enterocolitis
(NEC)Toxoplasma
infection
Genetically-induced colitis
Irritable
bowel syndrome
(IBS)
Colorectal cancer
Antibiotics
O2
Citrobacter
Infection
✔
Is there a common driver for gut dysbiosis?
Mariana Byndloss
HIV
enteropathy
Dysbiosis Salmonella infection
O2
Chemically-induced colitis
Inflammatory
bowel disease
(IBD)
High-fat
diet
Necrotizing
enterocolitis
(NEC)Toxoplasma
infection
Genetically-induced colitis
Irritable
bowel syndrome
(IBS)
Colorectal cancer
Antibiotics
O2
Citrobacter
Infection
✔
✔
Is there a common driver for gut dysbiosis?
Fabian
Rivera-Chavez
Mariana Byndloss
HIV
enteropathy
Dysbiosis Salmonella infection
O2
Chemically-induced colitis
Inflammatory
bowel disease
(IBD)
High-fat
diet
Necrotizing
enterocolitis
(NEC)Toxoplasma
infection
Genetically-induced colitis
Irritable
bowel syndrome
(IBS)
Colorectal cancer
Antibiotics
O2
Citrobacter
Infection
O2✔
✔
✔
Is there a common driver for gut dysbiosis?
Christopher Lopez
Fabian
Rivera-Chavez
Mariana Byndloss
HIV
enteropathy
Oxygen as a driver of gut dysbiosis:
What can we learn about homeostasis?
Dysbiosis Salmonella infection
O2
Chemically-induced colitis
O2
Inflammatory
bowel disease
(IBD)
High-fat
diet
Necrotizing
enterocolitis
(NEC)Toxoplasma
infection
Genetically-induced colitis
O2
Irritable
bowel syndrome
(IBS)
Colorectal cancer
Antibiotics
O2
Citrobacter
Infection
O2✔
✔
✔✔
✔Sebastian E Winter
UT Southwestern
Medical Center
Christopher Lopez
Fabian
Rivera-Chavez
Mariana Byndloss
HIV
enteropathy
Peroxisome proliferator-activated receptor gamma (PPAR-γ)
PPAR-γ is mainly expressed in adipose tissue, macrophages and epithelial cells in the colon (colonocytes)
M1 macrophage
Nos2
IFN-γ
D-glucose pyruvate
O2
CO2
lactate
Anaerobic glycolysis
(Warburg effect)
iNOS
PPAR-γβ-oxidation
Nos2
STAT6
O2
CO2
Fatty
acids
M2 macrophage
O2
CO2
O2
β-oxidation
PPAR-γ
Clostridia
Butyrate
Complex
carbohydrates
WT Pparg
Moc
k
2017 Science 357: 570
Butyrate depeltion and inflammation cooperate to increase epithelial oxygenation
Pparg
(Ppargfl/flVillincre/- mice)
WT
(Ppargfl/flVillin-/- mice)
O2
O2
Inflammation
Anaerobic glycolysis
Glucose Lactate
O2
Clostridia
Butyrate
Complex
carbohydrates
PPAR-γXWT Pparg
1% D
SS
Moc
k
E. coliE. coli cydAB
1:1
E. coli cydAB
1:1
100
101
102
103WT Pparg
CI co
lon
co
nte
nts
(E. coli
wtvs.
cydA
B)
1% DSS: - +
Butyrate depeltion and inflammation cooperate to increase epithelial oxygenation
DSS 2017 Science 357: 570
Pparg
(Ppargfl/flVillincre/- mice)
WT
(Ppargfl/flVillin-/- mice)
O2
CO2
O2
Anaerobic glycolysis
β-oxidation
PPAR-γ
SCFAs
Clostridia
Butyrate
Complex
carbohydrates
How does antibiotic treatment generate an inflammatory signal?
Cec
alco
ncen
trat
ion
(μmol
/g)
Strep: - +
**
**
0.001
0.01
0.1
1
10
100
Acetate
Propionate
ADPATP
2017 Science 357: 570
Tregs
Inflammation 0
10
20
30
40
50
60
Strep: - +
CD
3+-e
nric
hed
CD
4+F
OX
P3+
cells
(% o
f tot
al C
D3+
-enr
iche
d co
loni
c ce
lls)
*
O2
CO2
O2
Anaerobic glycolysis
β-oxidation
PPAR-γ
SCFAs
Clostridia
Butyrate
Complex
carbohydrates
How does antibiotic treatment generate an inflammatory signal?
Tregs
Inflammation 0
10
20
30
40
50
60
Strep: - +
CD
3+-e
nric
hed
CD
4+F
OX
P3+
cells
(% o
f tot
al C
D3+
-enr
iche
d co
loni
c ce
lls)
*
0
10
20
30
40
50
Isotype
control
anti-
CD25C
D3+
-enr
iche
d C
D4+
FO
XP
3+ce
lls
(% o
f tot
al C
D3+
-enr
iche
d co
loni
c ce
lls)
*C
ecal
conc
entr
atio
n
(μmol
/g)
Strep: - +
**
**
0.001
0.01
0.1
1
10
100
Acetate
Propionate
ADPATP
2017 Science 357: 570
Streptomycin
O2
O2
Tregs
Inflammation
Anaerobic glycolysis
SCFAs Butyrate
Clostridia
Glucose Lactate
Enterobacteriaceae
X
XXO2
CI c
olon
con
tent
s
(wild
type
vs.
aer
obic
res
pira
tion
defic
ient
)
0
5
10
15
20
25
Isotype
control
anti-
CD25
WT Pparg
**
0
10
20
30
40
50
Isotype
control
anti-
CD25C
D3+
-enr
iche
d C
D4+
FO
XP
3+ce
lls
(% o
f tot
al C
D3+
-enr
iche
d co
loni
c ce
lls)
*
How does antibiotic treatment generate an inflammatory signal?
0
10
20
30
40
50
60
Strep: - +
CD
3+-e
nric
hed
CD
4+F
OX
P3+
cells
(% o
f tot
al C
D3+
-enr
iche
d co
loni
c ce
lls)
*
Cec
alco
ncen
trat
ion
(μmol
/g)
Strep: - +
**
**
0.001
0.01
0.1
1
10
100
Acetate
Propionate
Streptomycin
O2
O2
Tregs
Inflammation
Anaerobic glycolysis
SCFAs Butyrate
Clostridia
Glucose Lactate
Enterobacteriaceae
X
XXO2
CI c
olon
con
tent
s
(wild
type
vs. a
erob
ic r
espi
ratio
n de
ficie
nt)
0
5
10
15
20
25
Isotype
control
anti-
CD25
WT Pparg
**
1000-fold
10-fold
Colonization
resistance
NO3-
NO
NO3-
Nitrate
iNOS
ROS
Nos2
NO2-
Nitrite
narKnarGHJInarUnarZYWVnapFDAGHBC
Respiration drives post-antibiotic expansion of Enterobacteriaceae
?
Nos2
iNOS
Col
onoc
yte
Nos
2 m
RN
A
(fol
d-ch
ange
)
0
2
4
6
8*
Strep: - +
Day 3 after
strep
Streptomycin
O2
O2
Tregs
Inflammation
Anaerobic glycolysis
SCFAs Butyrate
Clostridia
Glucose Lactate
Enterobacteriaceae
X
XXO2
CI c
olon
con
tent
s
(wild
type
vs. a
erob
ic r
espi
ratio
n de
ficie
nt)
0
5
10
15
20
25
Isotype
control
anti-
CD25
WT Pparg
**
Respiration drives post-antibiotic expansion of Enterobacteriaceae
1000-fold
10-fold
?
Nos2
iNOS
NO3-
102
103
104
100
101
***
WT Pparg +
anti-CD25
CI in
fe
ce
s
(E. co
li w
tvs
.cyd
AB
napA
narG
narZ
) 105
E. coli cydAB
napA
narG
narZ
Nos2O2
CO2
O2
Anaerobic glycolysis
β-oxidation
PPAR-γ
SCFAsButyrate
Tregs
Inflammation
ADPATP
PPAR-γ signalling and Tregscooperate
to maintain gut homeostasis
anaerobiosis
Virtuous
PPAR-γ
cycle
Balancing our
microbial self
Immune
system
Can we remediate dysbiosis by reinstating epithelial control to limit the
flow of oxygen into the gut lumen?
Inflammatory
bowel disease
(IBD)Ulcerative colitis
DSS-induced colitis5-aminosalicylic acid
(5-ASA)
DSS induces colitis by triggering ER stressDSS
ER stress
DSS-induced colitis5-aminosalicylic acid
(5-ASA)O2
O2
CO2
Butyrate
Butyrate
ATPADP
Na+
Na+
Na+
O2
O2
Glucose
Glucose
Lactate
ATP
ADP
O2
Undifferentiated
colonocyte
10%
1%
0.1%O
2g
radie
nt
Exc
essi
ve in
test
inal
epith
elia
l rep
air
resp
onse
Co
lon
ic c
ryp
t h
yp
erp
lasia
DSS
ER stressDSS induces colonic crypt hyperplasia
5-aminosalicylic acid
(5-ASA)
O2
O2
Blood vessel
Undifferentiated
colonocyte
10%
1%
0.1%O
2g
radie
nt
Co
lon
ic c
ryp
t h
yp
erp
lasia
DSS
ER stress
5-aminosalicylic acid
(5-ASA)
Mock 2.5% DSSE
xces
sive
inte
stin
al
epith
elia
l rep
air
resp
onse
DSS increases epithelial oxygenation
E. coli
102
103
104
105
106
107
Mock 2.5% DSSE
. col
i in
colo
n co
nten
ts
CF
U/g
)
O2
Stephanie Cevallos
O2
O2
Blood vessel
Undifferentiated
colonocyte
10%
1%
0.1%O
2g
radie
nt
Co
lon
ic c
ryp
t h
yp
erp
lasia
DSS
ER stress
5-aminosalicylic acid
(5-ASA)
Mock 2.5% DSSE
xces
sive
inte
stin
al
epith
elia
l rep
air
resp
onse
5-ASA restores epithelial hypoxia
E. coli
2.5% DSS +
5-ASA
102
103
104
105
106
107
Mock 2.5% DSSE
. col
i in
colo
n co
nten
ts
CF
U/g
)
Control 5-ASA
O2
O2O2
O2
Blood vessel
Undifferentiated
colonocyte
10%
1%
0.1%O
2g
radie
nt
Co
lon
ic c
ryp
t h
yp
erp
lasia
E. coliNR
cydAB
iNOS
NO3-
DSS
ER stress
5-aminosalicylic acid
(5-ASA)
Exc
essi
ve in
test
inal
epith
elia
l rep
air
resp
onse
102
103
104
105
106
107
Mock 2.5% DSSE
. col
i in
colo
n co
nten
ts
CF
U/g
)
Control 5-ASA
5-ASA restores epithelial hypoxia
DSS-induced colitis
E. coli cydAB
napA
narG
narZ
O2
O2
Blood vessel
Undifferentiated
colonocyte
10%
1%
0.1%O
2g
radie
nt
Co
lon
ic c
ryp
t h
yp
erp
lasia
E. coli
DSS
ER stress
5-aminosalicylic acid
(5-ASA)
Exc
essi
ve in
test
inal
epith
elia
l rep
air
resp
onse
102
103
104
105
106
107
Mock 2.5% DSSE
. col
i in
colo
n co
nten
ts
CF
U/g
)
Control 5-ASA
5-ASA restores epithelial hypoxia
DSS-induced colitis
E. coli cydAB
napA
narG
narZ
1
10
100
1000
10000
102
103
101
1Mock DSS
CI i
n fe
ces
(wtv
s.cy
dAB
napA
narG
narZ
)
WT
DSS
Pparg
104
iNOS
NO3- O2
ControlNR
cydAB5-ASA
Nos2O2
CO2
O2
Anaerobic glycolysis
β-oxidation
PPAR-γ
SCFAsButyrate
Tregs
Inflammation
ADPATP
Gut homeostasis
anaerobiosis
Can we remediate dysbiosis by
reinstating epithelial control to
limit the flow of oxygen into the
gut lumen?
Nos2
O2
O2
Tregs
Inflammation
Anaerobic glycolysis
SCFAs Butyrate
Glucose Lactate
iNOS
XX
Nos2O2
CO2
O2
Anaerobic glycolysis
β-oxidation
PPAR-γ
SCFAsButyrate
Tregs
Inflammation
ADPATP
Gut homeostasis
Gut dysbiosis
anaerobiosis
Can we remediate dysbiosis by
reinstating epithelial control to
limit the flow of oxygen into the
gut lumen?
5-aminosalicylic acid
(5-ASA)
Gut dysbiosis: a microbial signature of
epithelial dysfunction
Nos2
O2
O2
Tregs
Inflammation
Anaerobic glycolysis
SCFAs Butyrate
Glucose Lactate
iNOS
XX
Nos2O2
CO2
O2
Anaerobic glycolysis
β-oxidation
PPAR-γ
SCFAsButyrate
Tregs
Inflammation
ADPATP
Gut homeostasis
Gut dysbiosis
anaerobiosis
Can we remediate dysbiosis by
reinstating epithelial control to
limit the flow of oxygen into the
gut lumen?
5-aminosalicylic acid
(5-ASA)
Torsten
Sterzenbach
Univ. Osnabrück,
Germany
Thank you
Collaborators
Renée Tsolis, Garry Adams,
Volkmar Heinrich, Charles
Bevins, Carlito Lebrilla, Oliver
Fiehn, Stephen McSorley,
Valley Stewart, John Roth
Helene
Andrews-
Polymenis
Texas A&M University
Sebastian E Winter
UT Southwestern
Medical Center
Robert A Kingsley
Quadram Institute,
UK
Çagla Tükel
Temple University
Manuela Raffatellu
UC San Diego
Marijke
Keestra-Gounder
University of Colorado
Denver
Tracy Nicholson
USDA, Ames
Robert Crawford
CSU Sacramanto
Parameth
Thiennimitr
Chiang
Mai Univ.
Thailand
Takeshi Haneda
Kitasato Univ.,
Japan
Renato Santos
UFMG, Brazil
Franziska Faber
Univ. Würzburg,
Germany
Christopher
Lopez,
Vanderbilt
Fabian
Rivera-Chavez,
Harvard