npj Parkinson s Disease,
Год журнала:
2020,
Номер
6(1)
Опубликована: Июнь 12, 2020
Abstract
In
Parkinson’s
disease
(PD),
gastrointestinal
features
are
common
and
often
precede
the
motor
signs.
Braak
colleagues
proposed
that
PD
may
start
in
gut,
triggered
by
a
pathogen,
spread
to
brain.
Numerous
studies
have
examined
gut
microbiome
PD;
all
found
it
be
altered,
but
inconsistent
results
on
associated
microorganisms.
Studies
date
been
small
(
N
=
20
306)
difficult
compare
or
combine
due
varied
methodology.
We
conducted
microbiome-wide
association
study
(MWAS)
with
two
large
datasets
for
internal
replication
333
507).
used
uniform
methodology
when
possible,
interrogated
confounders,
applied
statistical
tests
concordance,
followed
correlation
network
analysis
infer
interactions.
Fifteen
genera
were
at
significance
level,
both
datasets,
methods,
without
covariate
adjustment.
The
associations
not
independent,
rather
they
represented
three
clusters
of
co-occurring
Cluster
1
was
composed
opportunistic
pathogens
elevated
PD.
2
short-chain
fatty
acid
(SCFA)-producing
bacteria
reduced
3
carbohydrate-metabolizing
probiotics
Depletion
anti-inflammatory
SCFA-producing
levels
confirmatory.
Overabundance
is
an
original
finding
their
identity
provides
lead
experimentally
test
role
Signal Transduction and Targeted Therapy,
Год журнала:
2024,
Номер
9(1)
Опубликована: Фев. 16, 2024
Abstract
The
human
gastrointestinal
tract
is
populated
with
a
diverse
microbial
community.
vast
genetic
and
metabolic
potential
of
the
gut
microbiome
underpins
its
ubiquity
in
nearly
every
aspect
biology,
including
health
maintenance,
development,
aging,
disease.
advent
new
sequencing
technologies
culture-independent
methods
has
allowed
researchers
to
move
beyond
correlative
studies
toward
mechanistic
explorations
shed
light
on
microbiome–host
interactions.
Evidence
unveiled
bidirectional
communication
between
central
nervous
system,
referred
as
“microbiota–gut–brain
axis”.
microbiota–gut–brain
axis
represents
an
important
regulator
glial
functions,
making
it
actionable
target
ameliorate
development
progression
neurodegenerative
diseases.
In
this
review,
we
discuss
mechanisms
As
provides
essential
cues
microglia,
astrocytes,
oligodendrocytes,
examine
communications
microbiota
these
cells
during
healthy
states
Subsequently,
diseases
using
metabolite-centric
approach,
while
also
examining
role
microbiota-related
neurotransmitters
hormones.
Next,
targeting
intestinal
barrier,
blood–brain
meninges,
peripheral
immune
system
counteract
dysfunction
neurodegeneration.
Finally,
conclude
by
assessing
pre-clinical
clinical
evidence
probiotics,
prebiotics,
fecal
transplantation
A
thorough
comprehension
will
foster
effective
therapeutic
interventions
for
management
Gut,
Год журнала:
2020,
Номер
69(10), С. 1867 - 1876
Опубликована: Авг. 5, 2020
The
gut
microbiota
has
been
implicated
in
cancer
and
shown
to
modulate
anticancer
drug
efficacy.
Altered
is
associated
with
resistance
chemo
drugs
or
immune
checkpoint
inhibitors
(ICIs),
whereas
supplementation
of
distinct
bacterial
species
restores
responses
the
drugs.
Accumulating
evidence
revealed
potential
modulating
enhance
efficacy
Regardless
valuable
findings
by
preclinical
models
clinical
data
patients
cancer,
a
more
thorough
understanding
interactions
therapy
helps
researchers
identify
novel
strategy
for
prevention,
stratify
effective
treatment
reduce
complication.
In
this
review,
we
discuss
scientific
on
role
treatment,
highlight
latest
knowledge
technologies
leveraged
target
specific
bacteria
that
contribute
tumourigenesis.
First,
provide
an
overview
establishing
links
between
bacteria,
inflammation
treatment.
Second,
mechanisms
used
growth,
responses,
as
well
chemotherapeutic
ICIs.
Third,
demonstrate
various
approaches
their
translational
research.
Finally,
limitations
current
microbiome
research
context
ongoing
efforts
overcome
these
challenges
future
perspectives.
Acta Pharmaceutica Sinica B,
Год журнала:
2019,
Номер
10(1), С. 19 - 32
Опубликована: Дек. 10, 2019
Microbes
inhabiting
the
intestinal
tract
of
humans
represent
a
site
for
xenobiotic
metabolism.
The
gut
microbiome,
collection
microorganisms
in
gastrointestinal
tract,
can
alter
metabolic
outcome
pharmaceuticals,
environmental
toxicants,
and
heavy
metals,
thereby
changing
their
pharmacokinetics.
Direct
chemical
modification
xenobiotics
by
either
through
or
re-entering
via
enterohepatic
circulation,
lead
to
increased
metabolism
bioactivation,
depending
on
enzymatic
activity
within
microbial
niche.
Unique
enzymes
encoded
microbiome
include
those
that
reverse
modifications
imparted
host
detoxification
pathways.
Additionally,
limit
absorption
small
intestine
increasing
expression
cell–cell
adhesion
proteins,
supporting
protective
mucosal
layer,
and/or
directly
sequestering
chemicals.
Lastly,
gene
is
regulated
including
CYP450s,
multi-drug
resistance
transcription
factors
regulate
them.
While
affects
pharmacokinetics
xenobiotic,
also
influence
viability
microbiome.
Our
understanding
complex
interconnectedness
between
host,
will
advance
with
new
modeling
systems,
technology
development
refinement,
mechanistic
studies
focused
contribution
human
Parkinson's
disease
is
a
neurodegenerative
disorder
characterized
by
the
accumulation
of
intracellular
aggregates
misfolded
alpha-synuclein
along
cerebral
axis.
Several
studies
report
association
between
intestinal
dysbiosis
and
disease,
although
cause-effect
relationship
remains
to
be
established.
Herein,
gut
microbiota
composition
64
Italian
patients
with
51
controls
was
determined
using
next-generation
sequencing
approach.
A
real
metagenomics
shape
based
on
gas
chromatography-mass
spectrometry
also
investigated.
The
most
significant
changes
within
group
highlighted
reduction
in
bacterial
taxa,
which
are
linked
anti-inflammatory/neuroprotective
effects,
particularly
Lachnospiraceae
family
key
members,
such
as
Butyrivibrio,
Pseudobutyrivibrio,
Coprococcus,
Blautia
direct
evaluation
fecal
metabolites
revealed
several
classes
metabolites.
Changes
were
seen
lipids
(linoleic
acid,
oleic
succinic
sebacic
acid),
vitamins
(pantothenic
acid
nicotinic
amino
acids
(isoleucine,
leucine,
phenylalanine,
glutamic
pyroglutamic
acid)
other
organic
compounds
(cadaverine,
ethanolamine,
hydroxy
propionic
acid).
Most
modified
strongly
correlated
abundance
members
belonging
family,
suggesting
that
these
bacteria
correlate
altered
metabolism
rates
disease.IMPORTANCE
To
our
knowledge,
this
one
few
thus
far
correlates
analysis
disease.
Overall,
data
highlight
modifications
numerous
This
suggests
associated
dysregulation
involves
synergistic
microbes
favoring
homeostasis.
Interestingly,
short-chain
fatty
(SCFA)-producing
influenced
metabolomics
profile,
affecting
potential
protective
effects
Parkinson
group.
On
hand,
extensive
impact
has
at
level
metabolic
pathways
could
encourage
identification
specific
biomarkers
for
diagnosis
treatment
light
effect
drugs
have
microbiota.
European Journal of Pharmaceutical Sciences,
Год журнала:
2021,
Номер
162, С. 105812 - 105812
Опубликована: Март 20, 2021
The
absorption
of
oral
drugs
is
frequently
plagued
by
significant
variability
with
potentially
serious
therapeutic
consequences.
source
can
be
traced
back
to
interindividual
in
physiology,
differences
special
populations
(age-
and
disease-dependent),
drug
formulation
properties,
or
food-drug
interactions.
Clinical
evidence
for
the
impact
some
these
factors
on
pharmacokinetic
mounting:
e.g.
gastric
pH
emptying
time,
small
intestinal
fluid
pediatrics
elderly,
surgical
changes
gastrointestinal
anatomy.
However,
link
colonic
(transit
composition,
microbiome),
sex
(male
vs.
female)
gut-related
diseases
(chronic
constipation,
anorexia
cachexia)
has
not
been
firmly
established
yet.
At
same
a
way
decrease
provided
pharmaceutical
industry:
clinical
suggests
that
approaches
employed
during
development
exposure.
This
review
outlines
main
drivers
exposure
potential
overcome
them,
while
highlighting
existing
knowledge
gaps
guiding
future
studies
this
area.
Molecular Nutrition & Food Research,
Год журнала:
2020,
Номер
64(9)
Опубликована: Март 20, 2020
Abstract
The
full
consensus
on
the
role
of
dietary
polyphenols
as
human‐health‐promoting
compounds
remains
elusive.
two‐way
interaction
between
and
gut
microbiota
(GM)
(i.e.,
modulation
GM
by
their
catabolism
GM)
is
determinant
in
polyphenols’
effects.
identification
human
metabotypes
associated
with
a
differential
microbial
metabolism
has
opened
new
research
scenarios
to
explain
inter‐individual
variability
upon
consumption.
unequivocally
identified
so
far
are
those
involved
isoflavones
(equol
and(or)
O
‐desmethylangolesin
producers
versus
non‐producers)
ellagic
acid
(urolithin
metabotypes,
including
only
urolithin‐A
(UM‐A),
urolithin‐A,
isourolithin‐A,
urolithin‐B
(UM‐B),
non‐producers
(UM‐0)).
In
addition,
metabolites
(phenolic‐derived
postbiotics)
such
equol,
urolithins,
valerolactones,
enterolactone,
enterodiol,
8‐prenylnaringenin,
among
others,
can
exert
health
knowledge
updated
position
taken
here
i)
polyphenols,
ii)
evidence
phenolic‐derived
postbiotics
health,
iii)
biomarkers
clustering
individuals
depending
(metabotyping)
effects,
iv)
catecholamines
illustrate
intersection
personalized
nutrition
precision
medicine.
Microorganisms,
Год журнала:
2022,
Номер
10(9), С. 1838 - 1838
Опубликована: Сен. 14, 2022
Gut
bacteria
play
an
important
role
in
the
digestion
of
food,
immune
activation,
and
regulation
entero-endocrine
signaling
pathways,
but
also
communicate
with
central
nervous
system
(CNS)
through
production
specific
metabolic
compounds,
e.g.,
bile
acids,
short-chain
fatty
acids
(SCFAs),
glutamate
(Glu),
γ-aminobutyric
acid
(GABA),
dopamine
(DA),
norepinephrine
(NE),
serotonin
(5-HT)
histamine.
Afferent
vagus
nerve
(VN)
fibers
that
transport
signals
from
gastro-intestinal
tract
(GIT)
gut
microbiota
to
brain
are
linked
receptors
esophagus,
liver,
pancreas.
In
response
these
stimuli,
sends
back
entero-epithelial
cells
via
efferent
VN
fibers.
Fibers
not
direct
contact
wall
or
intestinal
microbiota.
Instead,
reach
100
500
million
neurons
enteric
(ENS)
submucosa
myenteric
plexus
wall.
The
modulation,
development,
renewal
ENS
controlled
by
microbiota,
especially
those
ability
produce
metabolize
hormones.
Signals
generated
hypothalamus
pituitary
adrenal
glands
hypothalamic
axis
(HPA).
SCFAs
produced
adhere
free
(FFARs)
on
surface
epithelial
(IECs)
interact
enter
circulatory
system.
alter
synthesis
degradation
neurotransmitters.
This
review
focuses
effect
have
neurotransmitters
vice
versa.
Signal Transduction and Targeted Therapy,
Год журнала:
2021,
Номер
6(1)
Опубликована: Фев. 24, 2021
Abstract
The
phenylalanine–tyrosine–dopa–dopamine
pathway
provides
dopamine
to
the
brain.
In
this
process,
tyrosine
hydroxylase
(TH)
is
rate-limiting
enzyme
that
hydroxylates
and
generates
levodopa
(
l
-dopa)
with
tetrahydrobiopterin
(BH
4
)
as
a
coenzyme.
Here,
we
show
oral
berberine
(BBR)
might
supply
H
•
through
dihydroberberine
(reduced
BBR
produced
by
bacterial
nitroreductase)
promote
production
of
BH
from
dihydrobiopterin;
increased
enhances
TH
activity,
which
accelerates
-dopa
gut
bacteria.
Oral
acts
in
way
similar
vitamins.
intestinal
bacteria
enters
brain
circulation
transformed
dopamine.
To
verify
gut–brain
dialog
activated
BBR’s
effect,
Enterococcus
faecalis
or
faecium
was
transplanted
into
Parkinson’s
disease
(PD)
mice.
significantly
ameliorated
PD
manifestation
mice;
additionally,
combination
showed
better
therapeutic
effect
than
alone.
Moreover,
2,4,6-trimethyl-pyranylium
tetrafluoroborate
(TMP-TFB)-derivatized
matrix-assisted
laser
desorption
mass
spectrometry
(MALDI-MS)
imaging
identified
elevated
striatal
levels
mouse
brains
,
strengthened
intensity
These
results
demonstrated
an
agonist
could
lead
gut.
Furthermore,
study
28
patients
hyperlipidemia
confirmed
blood/fecal
Hence,
improve
function
upregulating
biosynthesis
microbiota
vitamin-like
effect.