JAMA Neurology,
Год журнала:
2024,
Номер
81(9), С. 925 - 925
Опубликована: Июль 29, 2024
Importance
Dysbiosis
has
been
robustly
demonstrated
in
Parkinson
disease
(PD),
and
fecal
microbiota
transplantation
(FMT)
shown
promising
effects
preclinical
PD
models.
Objective
To
assess
the
safety
symptomatic
efficacy
of
colonic
single-dose
anaerobically
prepared
FMT.
Design,
Setting,
Participants
This
was
a
double-blind,
placebo-controlled,
randomized
clinical
trial
conducted
between
November
2020
June
2023
with
follow-up
period
12
months
at
4
hospitals
Finland.
Patients
aged
35
to
75
years
Hoehn
&
Yahr
stage
1-3
mild
moderate
symptom
burden
dysbiosis
were
included.
Of
229
patients
screened,
48
47
received
intervention.
One
patient
discontinued
due
worsening
symptoms.
Two
further
excluded
before
analysis
45
included
intention-to-treat
analysis.
Intervention
2:1
ratio
receive
FMT
or
placebo
via
colonoscopy.
Main
Outcomes
Measures
The
primary
end
point
change
Movement
Disorder
Society
Unified
Parkinson’s
Disease
Rating
Scale
parts
I-III
(part
III
off
medication)
6
months.
Safety
assessed
by
recording
adverse
events
(AEs).
Results
median
(IQR)
age
65
(52.5-70.0)
group
66
(59.25-69.75)
group;
9
(60.0%)
16
(53.3%)
male
group,
respectively.
outcome
did
not
differ
groups
(0.97
points,
95%
CI,
−5.10
7.03,
P
=
.75).
Gastrointestinal
AEs
more
frequent
(16
[53%]
vs
1
[7%];
.003).
Secondary
outcomes
post
hoc
analyses
showed
stronger
increase
dopaminergic
medication
improvement
certain
motor
nonmotor
group.
Microbiota
changes
pronounced
after
but
differed
donor.
Nevertheless,
status
reversed
frequently
Conclusions
Relevance
safe
offer
clinically
meaningful
improvements.
Further
studies—for
example,
through
modified
approaches
bowel
cleansing—are
warranted
regarding
specific
impact
donor
composition
conversion
on
as
well
needs
PD.
Trial
Registration
ClinicalTrials.gov
Identifier:
NCT04854291
Nature Reviews Gastroenterology & Hepatology,
Год журнала:
2024,
Номер
21(4), С. 222 - 247
Опубликована: Фев. 14, 2024
Crosstalk
between
gut
and
brain
has
long
been
appreciated
in
health
disease,
the
microbiota
is
a
key
player
communication
these
two
distant
organs.
Yet,
mechanisms
through
which
influences
development
function
of
gut–brain
axis
remain
largely
unknown.
Barriers
present
are
specialized
cellular
interfaces
that
maintain
strict
homeostasis
different
compartments
across
this
axis.
These
barriers
include
epithelial
barrier,
blood–brain
barrier
blood–cerebrospinal
fluid
barrier.
ideally
positioned
to
receive
communicate
microbial
signals
constituting
gateway
for
gut–microbiota–brain
communication.
In
Review,
we
focus
on
how
modulation
by
can
constitute
an
important
channel
Moreover,
malfunction
upon
alterations
composition
could
form
basis
various
conditions,
including
often
comorbid
neurological
gastrointestinal
disorders.
Thus,
should
unravelling
molecular
move
from
simplistic
framing
as
'leaky
gut'.
A
mechanistic
understanding
barriers,
especially
during
critical
windows
development,
be
aetiology
The
modulator
This
Review
provides
overview
examines
role
disease.
Signal Transduction and Targeted Therapy,
Год журнала:
2023,
Номер
8(1)
Опубликована: Дек. 6, 2023
Gut-liver-brain
axis
is
a
three-way
highway
of
information
interaction
system
among
the
gastrointestinal
tract,
liver,
and
nervous
systems.
In
past
few
decades,
breakthrough
progress
has
been
made
in
gut
liver
brain
axis,
mainly
through
understanding
its
formation
mechanism
increasing
treatment
strategies.
this
review,
we
discuss
various
complex
networks
including
barrier
permeability,
hormones,
microbial
metabolites,
vagus
nerve,
neurotransmitters,
immunity,
toxic
β-amyloid
(Aβ)
metabolism,
epigenetic
regulation
gut-liver-brain
axis.
Some
therapies
containing
antibiotics,
probiotics,
prebiotics,
synbiotics,
fecal
microbiota
transplantation
(FMT),
polyphenols,
low
FODMAP
diet
nanotechnology
application
regulate
Besides,
some
special
treatments
targeting
gut-liver
include
farnesoid
X
receptor
(FXR)
agonists,
takeda
G
protein-coupled
5
(TGR5)
glucagon-like
peptide-1
(GLP-1)
antagonists
fibroblast
growth
factor
19
(FGF19)
analogs.
Targeting
gut-brain
embraces
cognitive
behavioral
therapy
(CBT),
antidepressants
tryptophan
metabolism-related
therapies.
liver-brain
contains
Aβ
future,
better
interactions
will
promote
development
novel
preventative
strategies
discovery
precise
therapeutic
targets
multiple
diseases.
Molecular Psychiatry,
Год журнала:
2023,
Номер
28(9), С. 3625 - 3637
Опубликована: Сен. 1, 2023
Abstract
The
human
body
harbors
a
diverse
ecosystem
of
microorganisms,
including
bacteria,
viruses,
and
fungi,
collectively
known
as
the
microbiota.
Current
research
is
increasingly
focusing
on
potential
association
between
microbiota
various
neuropsychiatric
disorders.
resides
in
parts
body,
such
oral
cavity,
nasal
passages,
lungs,
gut,
skin,
bladder,
vagina.
gut
gastrointestinal
tract
has
received
particular
attention
due
to
its
high
abundance
role
psychiatric
neurodegenerative
However,
presents
other
tissues,
though
less
abundant,
also
plays
crucial
immune
system
homeostasis,
thus
influencing
development
progression
For
example,
imbalance
associated
periodontitis
might
increase
risk
for
Additionally,
studies
using
postmortem
brain
samples
have
detected
widespread
presence
bacteria
brains
patients
with
Alzheimer’s
disease.
This
article
provides
an
overview
emerging
host
disorders
discusses
future
directions,
underlying
biological
mechanisms,
reliable
biomarkers
microbiota,
microbiota-targeted
interventions,
this
field.
Translational Neurodegeneration,
Год журнала:
2023,
Номер
12(1)
Опубликована: Дек. 15, 2023
Parkinson's
disease
(PD)
is
one
of
the
most
prevalent
neurodegenerative
diseases.
The
typical
symptomatology
PD
includes
motor
symptoms;
however,
a
range
nonmotor
symptoms,
such
as
intestinal
issues,
usually
occur
before
symptoms.
Various
microorganisms
inhabiting
gastrointestinal
tract
can
profoundly
influence
physiopathology
central
nervous
system
through
neurological,
endocrine,
and
immune
pathways
involved
in
microbiota-gut-brain
axis.
In
addition,
extensive
evidence
suggests
that
gut
microbiota
strongly
associated
with
PD.
This
review
summarizes
latest
findings
on
microbial
changes
their
clinical
relevance,
describes
underlying
mechanisms
which
bacteria
may
mediate
PD,
discusses
correlations
between
microbes
anti-PD
drugs.
this
outlines
status
research
therapies
for
future
directions
PD-gut
research.
Journal of Parkinson s Disease,
Год журнала:
2024,
Номер
14(3), С. 467 - 482
Опубликована: Март 26, 2024
The
discovery
of
a
pathogenic
variant
in
the
alpha-synuclein
(SNCA)
gene
Contursi
kindred
1997
indisputably
confirmed
genetic
cause
subset
Parkinson’s
disease
(PD)
patients.
Currently,
variants
one
seven
established
PD
genes
or
strongest
known
risk
factor
gene,
GBA1,
are
identified
∼15%
patients
unselected
for
age
at
onset
and
family
history.
In
this
Debate
article,
we
highlight
multiple
avenues
research
that
suggest
an
important
-
some
cases
even
predominant
role
genetics
aetiology,
including
familial
clustering,
high
rates
monogenic
selected
populations,
complete
penetrance
with
certain
forms.
At
first
sight,
steep
increase
prevalence
exceeding
other
neurodegenerative
diseases
may
argue
against
etiology.
Notably,
principal
contribution
is
conferred
by
LRRK2
GBA1
and,
both
cases,
characterized
overall
late
age-related
penetrance.
addition,
polygenic
plays
considerable
PD.
However,
it
likely
that,
majority
patients,
complex
interplay
aging,
genetic,
environmental,
epigenetic
factors
leads
to
development.
Translational Neurodegeneration,
Год журнала:
2024,
Номер
13(1)
Опубликована: Фев. 27, 2024
The
aetiologies
and
origins
of
neurodegenerative
diseases,
such
as
Alzheimer's
disease
(AD),
Parkinson's
(PD),
amyotrophic
lateral
sclerosis
(ALS)
Huntington's
(HD),
are
complex
multifaceted.
A
growing
body
evidence
suggests
that
the
gut
microbiome
plays
crucial
roles
in
development
progression
diseases.
Clinicians
have
come
to
realize
therapeutics
targeting
potential
halt
This
narrative
review
examines
alterations
AD,
PD,
ALS
HD,
highlighting
close
relationship
between
brain
Processes
mediate
microbiome-brain
communication
including
immunological,
vagus
nerve
circulatory
pathways,
evaluated.
Furthermore,
we
summarize
for
diseases
modify
its
metabolites,
diets,
probiotics
prebiotics,
microbial
antibacterials
faecal
transplantation.
Finally,
current
challenges
future
directions
discussed.
Abstract
Parkinson's
disease
(PD)
is
characterised
neuropathologically
by
the
degeneration
of
dopaminergic
neurons
in
ventral
midbrain,
accumulation
α-synuclein
(α-syn)
aggregates
neurons,
and
chronic
neuroinflammation.
In
past
two
decades,
vitro,
ex
vivo
studies
have
consistently
shown
involvement
inflammatory
responses
mediated
microglia
astrocytes,
which
may
be
elicited
pathological
α-syn
or
signals
from
affected
other
cell
types,
are
directly
linked
to
neurodegeneration
development.
Besides
prominent
immune
alterations
seen
central
nervous
system
(CNS),
including
infiltration
T-cells
into
brain,
more
recent
demonstrated
important
changes
peripheral
profile
within
both
innate
adaptive
compartments,
particularly
involving
monocytes,
CD4+
CD8+
T-cells.
This
review
aims
integrate
consolidated
understanding
immune-related
processes
underlying
pathogenesis
PD,
focusing
on
cells,
neuron-glia
crosstalk
as
well
central-peripheral
interaction
during
development
PD.
Our
analysis
seeks
provide
a
comprehensive
view
emerging
knowledge
mechanisms
immunity
PD
implications
this
for
better
overall
disease.
