ESC Heart Failure,
Journal Year:
2025,
Volume and Issue:
unknown
Published: March 17, 2025
Abstract
Aims
Gut
dysbiosis
is
proven
to
be
involved
in
the
pathogenesis
and
progression
of
heart
failure
(HF).
Hindering
detrimental
effects
gut‐heart
axis
an
emerging
trend.
Our
goal
investigate
causal
relationship
between
gut
microbiota
HF,
with
aim
facilitating
future
exploration
microbiome‐targeted
approaches
prevent
delay
HF.
Methods
results
Two‐sample
Mendelian
randomization
(MR)
analysis
was
applied
association
microbiome
HF
among
individuals
European
ancestry.
Genetic
variants
associated
196
bacterial
taxa
from
MiBioGen
consortium
were
used
as
exposure
data,
summary
statistics
for
derived
Heart
Failure
Molecular
Epidemiology
Therapeutic
Targets
(HERMES)
outcome
data.
Five
MR
methods
applied,
including
inverse
variance
weighted,
maximum
likelihood,
MR‐Egger,
weighted
median,
mode.
Reverse
causality
instrumental
variables
(IVs)
tested
by
Steiger
test
directionality.
Strength
IVs
evaluated
F
‐statistics.
Cochrane's
Q
test,
MR‐Egger
regression
analysis,
Pleiotropy
RESidual
Sum
Outlier
(MR‐PRESSO)
tests
detect
heterogeneity
pleiotropy.
Leave‐one‐out
method
testing
stability
results.
Seven
microbiomes
found
them
higher
risks
developing
these
included
Order_Selenomonadales
(odds
ratio
[OR]
=
1.11,
P
0.024),
Family_Peptococcaceae
(OR
1.07,
0.045),
Genus_
Eubacterium
eligens
group
1.14,
0.022),
oxidoreducens
1.12,
0.011)
Genus_Flavonifractor
0.012).
Genus_Anaerostipes
Order_Bacillales
lower
0.90,
0.014;
OR
0.95,
0.042,
respectively).
Evidence
pleiotropy
or
not
observed.
Conclusions
We
identified
seven
intestinal
that
causally
at
level
gene
prediction.
This
study
will
help
discovery
potential
preventive
therapeutic
targets
Journal of Cellular and Molecular Medicine,
Journal Year:
2025,
Volume and Issue:
29(1)
Published: Jan. 1, 2025
ABSTRACT
This
study
aims
to
elucidate
the
potential
genetic
commonalities
between
metabolic
syndrome
(MetS)
and
rheumatic
diseases
through
a
disease
interactome
network,
according
publicly
available
large‐scale
genome‐wide
association
studies
(GWAS).
The
analysis
included
linkage
disequilibrium
score
regression
analysis,
cross
trait
meta‐analysis
colocalisation
identify
common
overlap.
Using
modular
partitioning,
network‐based
two
proteins
in
protein–protein
interaction
set
was
divided
quantified.
Clinical
samples
from
public
databases
were
used
confirm
mapped
genes.
Mendelian
randomisation
analyses
conducted
using
instrumental
variables
for
causal
inference.
MetS
rheumatoid
arthritis
(RA),
ankylosing
spondylitis
(AS),
systemic
lupus
erythematosus
(SLE),
Sjogren's
(SS)
their
primary
module
networks
shared
topological
overlap
correlation.
Functional
highlighted
significance
of
these
targets
processes
such
as
diverse
array
pathways
involving
glucose,
lipids,
energy,
protein
transport,
inflammatory
response,
autophagy
cytokine
regulation,
elucidating
which
intersects
with
diseases.
Causal
associations
determined
phenotypes
persistence
effects
on
remained
evident
even
after
adjusting
alcohol
consumption
smoking.
We
have
specific
Several
genes
(e.g.,
PRRC2A,
PSMB8,
BAG6,
GPSM3,
PBX2,
etc.)
been
identified
molecular
RA,
AS,
SLE
SS,
may
serve
treatments.
Arthritis & Rheumatology,
Journal Year:
2023,
Volume and Issue:
75(8), P. 1334 - 1343
Published: April 11, 2023
The
positive
association
between
rheumatoid
arthritis
(RA)
and
osteoporosis
has
been
reported
in
previous
observational
studies,
but
the
causal
relationship
remains
unclear.
This
study
was
undertaken
to
investigate
whether
RA
causally
associated
with
Japanese
populations
using
Mendelian
randomization
(MR)
analyses.Publicly
available
summarized
data
from
genome-wide
studies
(GWAS)
on
(4,199
cases
208,254
controls)
(7,788
204,665
were
obtained
BioBank
Japan.
Eleven
RA-related
single-nucleotide
polymorphisms
(P
<
5×10-8
)
selected
as
instrumental
variables.
We
used
inverse
variance-weighted
method
primary
calculate
odds
ratios
(ORs)
95%
confidence
intervals
(95%
CIs).
also
MR-Egger's
method,
weighted
median,
mode
determine
robustness
of
main
results.
To
partially
test
horizontal
pleiotropy,
we
intercept
pleiotropy
residual
sum
outlier
(MRPRESSO)
test.Using
showed
that
genetically
predicted
positively
(OR
1.10,
CI
1.06-1.14,
P
0.001).
robust
when
tested
results
1.09,
1.03-1.16,
=
0.023),
median
1.04-1.15,
0.001),
1.08,
1.03-1.13,
0.012).
Horizontal
not
detected
0.737)
by
or
MRPRESSO
test.Our
show
a
potential
osteoporosis.
finding
consistent
different
MR
methods
sensitivity
analysis.
Further
are
needed
GWAS
more
details
performed
other
East
Asian/Japanese
available.
Frontiers in Immunology,
Journal Year:
2023,
Volume and Issue:
14
Published: Aug. 30, 2023
While
targeted
systemic
inflammatory
modulators
show
promise
in
preventing
chronic
kidney
disease
(CKD)
progression,
the
causal
link
between
specific
factors
and
CKD
remains
uncertain.Using
a
genome-wide
association
study
of
41
serum
cytokines
from
8,293
Finnish
individuals,
we
conducted
bidirectional
two-sample
Mendelian
randomization
(MR)
analysis.
In
addition,
genetically
predicted
associations
5
phenotypes,
including
CKD,
estimated
glomerular
filtration
rate
(eGFR),
dialysis,
rapid
progression
decline
eGFR.
Inverse
variance
weighting
(IVW)
served
as
primary
MR
method,
while
MR-Egger,
weighted
median,
MR-pleiotropy
residual
sum
outlier
(MR-PRESSO)
were
utilized
for
sensitivity
Cochrane's
Q
test
heterogeneity.
Leave-one-out
method
ensured
stability
results,
Bonferroni
correction
assessed
relationship
strength.Seventeen
associated
with
diverse
renal
outcomes.
Among
them,
after
test,
higher
tumor
necrosis
factor
alpha
levels
decrease
eGFR
(OR
=
1.064,
95%
CI
1.028
-
1.103,
P
0.001),
interleukin-4
an
increase
(β
0.003,
0.001
0.005,
0.002),
growth
regulated
oncogene
(GROα)
increased
risk
(OR=1.035,
1.012
1.058,
0.003).
contrast,
genetic
susceptibility
to
was
GROa,
may
lead
stem
cell
factor.
We
did
not
find
presence
horizontal
pleiotropy
during
analysis.We
discovered
causally
related
that
contribute
initiation
at
prediction
level.
Frontiers in Microbiology,
Journal Year:
2023,
Volume and Issue:
14
Published: July 18, 2023
The
gut
microbiome
is
closely
related
to
gastrointestinal
(GI)
cancer,
but
the
causality
of
with
GI
cancer
has
yet
be
fully
established.
We
conducted
this
two-sample
Mendelian
randomization
(MR)
study
reveal
potential
causal
effect
microbiota
on
cancer.Summary-level
genetic
data
were
derived
from
MiBioGen
consortium
and
Dutch
Microbiome
Project.
Summary
statistics
six
cancers
drawn
United
Kingdom
Biobank.
Inverse-variance-weighted
(IVW),
MR-robust
adjusted
profile
score
(MR-RAPS),
weighted-median
(WM)
methods
used
evaluate
link
between
cancer.
In
addition,
we
performed
sensitivity
analyses
reverse
MR
analyses.We
identified
associations
21
bacterial
taxa
(values
p
<
0.05
in
all
three
methods).
Among
them,
phylum
Verrucomicrobia
(OR:
0.17,
95%
CI:
0.05-0.59,
=
0.005)
retained
a
strong
negative
association
intrahepatic
cholangiocarcinoma
after
Bonferroni
correction,
whereas
order
Bacillales
1.67,
1.23-2.26,
0.001)
positive
pancreatic
Reverse
indicated
that
was
associated
17
microbial
methods,
among
inverse
colorectal
family
Clostridiaceae1
0.91,
0.86-0.96,
by
correction.Our
implicates
effects
specific
potentially
providing
new
insights
into
prevention
treatment
through
bacteria.
Metabolism and Target Organ Damage,
Journal Year:
2024,
Volume and Issue:
4(2)
Published: April 7, 2024
Chronic
kidney
disease
(CKD)
and
nonalcoholic
fatty
liver
(NAFLD),
metabolic
dysfunction-associated
(MAFLD)
steatotic
(MASLD)
account
for
substantial
financial
burden
worldwide.
These
alarming
features
call
enhanced
efforts
to
prevent
manage
the
development
progression
of
CKD.
Accumulating
evidence
supporting
a
causal
role
NAFLD/MAFLD/MASLD-in
CKD
opens
new
horizons
achieve
this
aim.
Recent
epidemiological
studies
meta-analyses
exploring
association
NAFLD/MAFLD/MASLD
with
characteristics
associated
odds
incident
are
discussed.
The
involved
pathomechanisms,
including
common
soil
hypothesis,
genetics,
gut
dysbiosis,
portal
hypertension,
examined
in
detail.
Finally,
lifestyle
changes
(diet
physical
exercise),
direct
manipulation
microbiota,
drug
approaches
involving
statins,
renin-angiotensin-aldosterone
system
inhibitors,
GLP-1
Receptor
Agonists,
Sodium-glucose
cotransporter-2,
pemafibrate,
vonafexor
within
context
prevention
management
among
those
NAFLD/MAFLD/MASLD.
evolving
nomenclature
may
generate
confusion
practicing
clinicians
investigators.
However,
comparative
investigating
pros
contra
different
nomenclatures
identify
most
useful
definitions
strategies
identify,
prevent,
halt
onset
Frontiers in Microbiology,
Journal Year:
2023,
Volume and Issue:
14
Published: July 24, 2023
Increasing
evidence
from
observational
studies
and
clinical
experimentation
has
indicated
a
link
between
the
gut
microbiotas
(GMs)
polycystic
ovary
syndrome
(PCOS),
however,
causality
direction
of
microbiome
PCOS
remains
to
be
established.
We
conducted
comprehensive
search
four
databases-PubMed,
Cochrane
Library,
Web
Science,
Embase
up
until
June
1,
2023,
subjected
results
meta-analysis.
In
this
study,
bidirectional
two-sample
Mendelian
randomization
(MR)
analysis
was
employed
investigate
impact
microbiota
on
(PCOS).
The
genome-wide
association
study
(GWAS)
data
for
comprised
113,238
samples,
while
GWAS
were
derived
MiBioGen
consortium,
encompassing
total
sample
size
18,340
individuals.
As
largest
dataset
its
kind,
represents
most
meta-analysis
concerning
composition
date.
Single
nucleotide
polymorphisms
(SNPs)
selected
as
instrumental
variables
at
various
taxonomic
levels,
including
Phylum,
Class,
Order,
Family,
Genus.
causal
associations
exposures
outcomes
assessed
using
established
MR
methods.
To
correct
multiple
testing,
false
discovery
rate
(FDR)
method
applied.
reliability
potential
biases
evaluated
through
sensitivity
F-statistics.
incorporated
20
that
met
criteria,
revealing
close
specific
species.
per
our
analysis,
we
identified
six
At
genus
level,
Actinomyces
(ORIVW
=
1.369,
FDR
0.040),
Streptococcus
1.548,
0.027),
Ruminococcaceae
UCG-005
1.488,
0.028)
risk
factors
PCOS.
Conversely,
Candidatus
Soleaferrea
0.723,
Dorea
0.580,
0.032),
UCG-011
0.732,
0.030)
found
protective
against
Furthermore,
MR-PRESSO
global
test
MR-Egger
regression
not
affected
by
horizontal
pleiotropy
(p
>
0.05).
Finally,
leave-one-out
corroborated
robustness
findings.
Both
indicates
there
is
relationship
PCOS,
which
may
contribute
providing
novel
insights
development
new
preventive
therapeutic
strategies
International Journal of Molecular Sciences,
Journal Year:
2024,
Volume and Issue:
25(3), P. 1716 - 1716
Published: Jan. 31, 2024
Regardless
of
the
currently
proposed
best
medical
treatment
for
heart
failure
patients,
morbidity
and
mortality
rates
remain
high.
This
is
due
to
several
reasons,
including
interaction
between
oral
cardiac
drug
administration
gut
microbiota.
The
relation
drugs
(especially
antibiotics)
microbiota
well
established,
but
it
also
known
that
more
than
24%
non-antibiotic
affect
microbiota,
altering
microbe's
environment
its
metabolic
products.
Heart
lies
mainly
in
blockage
neuro-humoral
hyper-activation.
There
debate
as
whether
heart-failure-specific
can
totally
block
this
hyper-activation,
or
so-called
intestinal
dysbiosis
commonly
observed
group
patients
their
action.
Although
there
are
reports
indicating
a
strong
drug-gut
interplay,
little
about
chronic
failure.
In
review,
we
review
contemporary
data
on
topic
infancy.
We
aim
produce
scientific
thoughts
questions
provide
reasoning
further
clinical
investigation.
Frontiers in Microbiology,
Journal Year:
2024,
Volume and Issue:
15
Published: Feb. 2, 2024
Background
An
increasing
body
of
evidence
suggests
a
profound
interrelation
between
the
microbiome
and
sleep-related
concerns.
Nevertheless,
current
observational
studies
can
merely
establish
their
correlation,
leaving
causality
unexplored.
Study
objectives
To
ascertain
whether
specific
gut
microbiota
are
causally
linked
to
seven
characteristics
propose
potential
strategies
for
insomnia
prevention.
Methods
The
study
employed
an
extensive
dataset
genetic
variations
from
MiBioGen
alliance,
encompassing
18,340
individuals.
Taxonomic
classification
was
conducted,
identifying
131
genera
196
bacterial
taxa
analysis.
Sleep-related
phenotype
(SRP)
data
were
sourced
IEU
OpenGWAS
project,
covering
traits
such
as
insomnia,
chronotype,
snoring.
Instrumental
variables
(IVs)
selected
based
on
criteria,
including
locus-wide
significance,
linkage
disequilibrium
calculations,
allele
frequency
thresholds.
Statistical
methods
explore
causal
relationships,
inverse
variance
weighted
(IVW),
MR-Egger,
median,
Mode.
Sensitivity
analyses,
pleiotropy
assessments,
Bonferroni
corrections
ensured
result
validity.
Reverse
analysis
adherence
STROBE-MR
guidelines
conducted
bolster
study’s
rigor.
Results
Bidirectional
Mendelian
randomization
(MR)
reveals
causative
interplay
phenotypes.
Notably,
outcomes
rigorously
Bonferroni-corrected
examination
illuminate
correlations
amid
precise
compositions
intestinal
slumber-associated
parameters.
Elevated
abundance
within
taxonomic
ranks
class
Negativicutes
order
Selenomonadales
markedly
associated
with
heightened
susceptibility
severe
(OR
=
1.03,
95%
CI:
1.02–1.05,
p
0.0001).
Conversely,
augmented
representation
phylum
Lentisphaerae
stands
in
concord
protracted
sleep
duration
1.02,
1.01–1.04,
0.0005).
Furthermore,
exposure
genus
Senegalimassilia
exhibits
ameliorate
manifestation
snoring
symptoms
0.98,
0.96–0.99,
Conclusion
This
has
unveiled
relationship
SRPs,
bestowing
significant
latent
value
upon
future
endeavors
both
foundational
research
clinical
therapy.
Frontiers in Immunology,
Journal Year:
2024,
Volume and Issue:
15
Published: Feb. 8, 2024
Background
Despite
establishing
an
association
between
gut
microbiota
and
spondyloarthritis
(SpA)
subtypes,
the
causal
relationship
them
remains
unclear.
Methods
Gut
data
were
obtained
from
MiBioGen
collaboration,
SpA
genome-wide
study
(GWAS)
summary
FinnGen
collaboration.
We
conducted
a
two-sample
Mendelian
randomization
(MR)
analysis
using
inverse-variance-weighted
method
supplemented
with
four
additional
MR
methods
(MR-Egger,
weighted
median,
simple
mode,
mode).
Pleiotropy
heterogeneity
also
assessed.
Reverse
was
used
to
detect
reverse
relationships.
Results
identified
23
links
specific
taxa
levels.
Of
these,
22
displayed
nominal
associations,
only
one
demonstrated
robust
connection.
Actinobacteria
id.419
increased
risk
of
ankylosing
spondylitis
(AS)
(odds
ratio
(OR)
=
1.86
(95%
confidence
interval
(CI):
1.29–2.69);
p
8.63
E
−04).
The
family
Rikenellaceae
id.967
associated
reduced
both
AS
(OR
0.66
CI:
0.47–0.93);
1.81
−02)
psoriatic
arthritis
0.70
0.50–0.97);
3.00
−02).
Bacillales
id.1674
1.23
1.00–1.51);
4.94
decreased
enteropathic
0.56
0.35–0.88);
1.14
Directional
pleiotropy,
or
heterogeneity,
not
observed.
No
associations
observed
diseases
microbiota.
Conclusion
Our
suggested
genetic-level
SpA,
providing
insights
into
underlying
mechanisms
behind
development
mediated
by
Gene,
Journal Year:
2024,
Volume and Issue:
911, P. 148320 - 148320
Published: March 5, 2024
Non-Hodgkin's
lymphoma
incidence
rates
vary
between
European
and
Asian
populations.
The
reasons
remain
unclear.
This
two-sample
two-step
Mendelian
randomisation
(MR)
study
aimed
to
investigate
the
causal
relationship
anthropometric
indicators
(AIs)
diffuse
large
B-cell
(DLBCL)
follicular
(FL)
possible
mediating
role
of
basal
metabolic
rate
(BMR)
in
Europe.