Redox Biology,
Journal Year:
2017,
Volume and Issue:
12, P. 505 - 521
Published: March 23, 2017
Changes
in
plasma
concentration
of
small
organic
metabolites
could
be
due
to
their
altered
production
or
urinary
excretion
and
changes
urine
may
the
filtered
load,
tubular
reabsorption,
and/or
volume.
Therefore,
these
factors
should
considered
interpretation
observed
target
metabolite(s).
Fasting
samples
from
180
CKD
patients
120
age-matched
healthy
controls
were
determined
by
UPLC-HDMS-metabolomics
quantitative
real-time
RT-PCR
techniques.
Compared
with
controls,
showed
activation
NF-κB
up-regulation
pro-inflammatory
pro-oxidant
mRNA
protein
expression
as
well
down-regulation
Nrf2-associated
anti-oxidant
gene
expression,
accompanied
activated
canonical
Wnt/β-catenin
signaling.
124
128
identified
40
significantly
both
urine.
Plasma
25
distinctly
different
between
controls.
They
related
amino
acid,
methylamine,
purine
lipid
metabolisms.
Logistic
regression
four
five
metabolites.
Parts
them
good
correlated
eGFR
serum
creatinine.
5-Methoxytryptophan
homocystine
citrulline
Clinical
incorporated
establish
predictive
models.
The
enhanced
metabolite
model
5-methoxytryptophan,
have
satisfactory
accuracy,
sensitivity
specificity
for
CKD.
dysregulation
was
additional
GFR-associated
biomarker
candidates
indicating
advanced
renal
injury.
caused
metabolome,
inflammatory/oxidative
pathway
signaling
suppression
antioxidant
pathway.
•
Chronic
kidney
disease
(CKD)
is
a
serious
public
health
problem.
Redox
wnt/β-catenin
studied
patients.
phenotypes
metabolomics.
Four
GFR
Circulation Research,
Journal Year:
2017,
Volume and Issue:
120(7), P. 1183 - 1196
Published: March 30, 2017
Significant
interest
in
recent
years
has
focused
on
gut
microbiota-host
interaction
because
accumulating
evidence
revealed
that
intestinal
microbiota
play
an
important
role
human
health
and
disease,
including
cardiovascular
diseases.
Changes
the
composition
of
associated
with
referred
to
as
dysbiosis,
have
been
linked
pathologies
such
atherosclerosis,
hypertension,
heart
failure,
chronic
kidney
obesity,
type
2
diabetes
mellitus.
In
addition
alterations
composition,
metabolic
potential
identified
a
contributing
factor
development
Recent
studies
can
elicit
variety
effects
host.
Indeed,
microbiome
functions
like
endocrine
organ,
generating
bioactive
metabolites,
impact
host
physiology.
Microbiota
interact
through
many
pathways,
trimethylamine/trimethylamine
Circulation Research,
Journal Year:
2014,
Volume and Issue:
116(3), P. 448 - 455
Published: Nov. 7, 2014
Trimethylamine-N-oxide
(TMAO),
a
gut
microbial-dependent
metabolite
of
dietary
choline,
phosphatidylcholine
(lecithin),
and
l-carnitine,
is
elevated
in
chronic
kidney
diseases
(CKD)
associated
with
coronary
artery
disease
pathogenesis.To
both
investigate
the
clinical
prognostic
value
TMAO
subjects
versus
without
CKD,
test
hypothesis
that
plays
direct
contributory
role
development
progression
renal
dysfunction.We
first
examined
relationship
between
fasting
plasma
all-cause
mortality
over
5-year
follow-up
521
stable
CKD
(estimated
glomerular
filtration
rate,
<60
mL/min
per
1.73
m(2)).
Median
level
among
was
7.9
μmol/L
(interquartile
range,
5.2-12.4
μmol/L),
which
markedly
higher
(P<0.001)
than
non-CKD
(n=3166).
Within
subjects,
(fourth
quartile)
2.8-fold
increased
risk.
After
adjustments
for
traditional
risk
factors,
high-sensitivity
C-reactive
protein,
estimated
levels
remained
predictive
(hazard
ratio,
1.93;
95%
confidence
interval,
1.13-3.29;
P<0.05).
provided
significant
incremental
(net
reclassification
index,
17.26%;
P<0.001
differences
area
under
receiver
operator
characteristic
curve,
63.26%
65.95%;
P=0.036).
Among
portend
poorer
prognosis
within
cohorts
high
low
cystatin
C.
In
animal
models,
choline
or
directly
led
to
progressive
tubulointerstitial
fibrosis
dysfunction.Plasma
are
patients
long-term
survival.
Chronic
exposures
increase
contributes
dysfunction
models.
Journal of Clinical Investigation,
Journal Year:
2014,
Volume and Issue:
124(10), P. 4204 - 4211
Published: Sept. 30, 2014
Our
group
recently
discovered
that
certain
dietary
nutrients
possessing
a
trimethylamine
(TMA)
moiety,
namely
choline/phosphatidylcholine
and
L-carnitine,
participate
in
the
development
of
atherosclerotic
heart
disease.
A
meta-organismal
pathway
was
elucidated
involving
gut
microbiota-dependent
formation
TMA
host
hepatic
flavin
monooxygenase
3-dependent
(FMO3-dependent)
TMA-N-oxide
(TMAO),
metabolite
shown
to
be
both
mechanistically
linked
atherosclerosis
whose
levels
are
strongly
cardiovascular
disease
(CVD)
risks.
Collectively,
these
studies
reveal
nutrient
precursors,
microbiota,
participants
along
may
serve
as
new
targets
for
prevention
treatment
CVD.
Annual Review of Nutrition,
Journal Year:
2017,
Volume and Issue:
37(1), P. 157 - 181
Published: July 18, 2017
Trimethylamine
N-oxide
(TMAO)
is
a
biologically
active
molecule
and
putative
promoter
of
chronic
diseases
including
atherosclerosis
in
humans.
Host
intestinal
bacteria
produce
its
precursor
trimethylamine
(TMA)
from
carnitine,
choline,
or
choline-containing
compounds.
Most
the
TMA
produced
passively
absorbed
into
portal
circulation,
hepatic
flavin-dependent
monooxygenases
(FMOs)
efficiently
oxidize
to
TMAO.
Both
observational
experimental
studies
suggest
strong
positive
correlation
between
increased
plasma
TMAO
concentrations
adverse
cardiovascular
events,
such
as
myocardial
infarction,
stroke,
death.
However,
clear
mechanistic
link
not
yet
validated.
Therefore,
it
debated
whether
are
cause
result
these
diseases.
Here,
we
have
tried
review
current
understanding
properties
physiological
functions
TMAO,
dietary
sources,
effects
on
human
metabolism.
Studies
that
describe
potential
role
etiology
other
also
discussed.
