Research Square (Research Square),
Journal Year:
2023,
Volume and Issue:
unknown
Published: June 27, 2023
Abstract
BACKGROUND
Although
previous
studies
have
suggested
a
close
association
between
gut
microbiota(GM)
and
intervertebral
disc
degeneration(IVDD),
the
causal
relationship
them
remains
unclear.Hence,we
thoroughly
investigate
their
by
means
of
two-sample
mendelian
randomization
(MR)
study,
aiming
to
determine
impact
microbiota
on
risk
developing
degeneration.
METHODS
Summary
data
from
genome-wide
(GWAS)
GM
(the
MiBioGen)
IVDD
FinnGen
biobank)
been
acquired.The
inverse
variance
weighted
(IVW)
method
was
utilized
as
primary
MR
analysis
approach.
Weighted
median
(WME),
MR-Egger
regression,
mode,
simple
mode
were
used
supplements.
The
pleiotropy
residual
sum
outlier
(MR-PRESSO)
regression
performed
assess
horizontal
pleiotropy.
Cochran's
Q
test
evaluated
heterogeneity.Leave-one-out
sensitivity
further
conducted
reliability
relationship.
A
reverse
potential
causation.
RESULTS
We
identified
nine
microbial
taxa
that
causally
associated
with
IVDD(
P
<
0.05).Following
Benjamini-Hochberg
corrected
test,
phylum
Bacteroidetes
higher
remained
significant(IVW
FDR-corrected
=
0.0365).
results
Cochrane
did
not
indicate
heterogeneity
(
>
0.05).
Additionally,
both
intercept
MR-PRESSO
global
revealed
our
influenced
Furthermore,
leave-one-out
substantiated
relationship.In
analysis,
no
evidence
found
suggest
has
an
microbiota.
CONCLUSION
Our
validate
particular
IVDD,
thus
providing
fresh
insights
into
microbiota-mediated
mechanism
laying
groundwork
for
research
targeted
preventive
measures.
Cancer Communications,
Journal Year:
2024,
Volume and Issue:
44(10), P. 1130 - 1167
Published: Aug. 1, 2024
The
intratumoral
microbiome
(TM)
refers
to
the
microorganisms
in
tumor
tissues,
including
bacteria,
fungi,
viruses,
and
so
on,
is
distinct
from
gut
circulating
microbiota.
TM
strongly
associated
with
tumorigenesis,
progression,
metastasis,
response
therapy.
This
paper
highlights
current
status
of
TM.
Tract
sources,
adjacent
normal
tissue,
circulatory
system,
concomitant
co-metastasis
are
main
origin
advanced
techniques
analysis
comprehensively
summarized.
Besides,
involved
progression
through
several
mechanisms,
DNA
damage,
activation
oncogenic
signaling
pathways
(phosphoinositide
3-kinase
[PI3K],
signal
transducer
activator
transcription
[STAT],
WNT/β-catenin,
extracellular
regulated
protein
kinases
[ERK]),
influence
cytokines
induce
inflammatory
responses,
interaction
microenvironment
(anti-tumor
immunity,
pro-tumor
microbial-derived
metabolites).
Moreover,
promising
directions
therapy
include
immunotherapy,
chemotherapy,
radiotherapy,
application
probiotics/prebiotics/synbiotics,
fecal
transplantation,
engineered
microbiota,
phage
therapy,
oncolytic
virus
inherent
challenges
clinical
also
review
provides
a
comprehensive
landscape
for
analyzing
TM,
especially
TM-related
mechanisms
TM-based
treatment
cancer.
Journal of Orthopaedic Surgery and Research,
Journal Year:
2023,
Volume and Issue:
18(1)
Published: June 16, 2023
Intervertebral
disc
degeneration
(IVDD)
has
become
a
serious
public
health
problem,
placing
heavy
burden
on
society
and
the
healthcare
system.
Its
pathogenesis
is
not
completely
clear
may
be
closely
related
to
mechanical
damage,
inflammatory
factors,
oxidative
stress
death
of
nucleus
pulposus
cells
(NPCs).
The
treatment
IVDD
mainly
includes
conservative
surgery.
Conservative
based
hormonal
anti-inflammatory
drugs
massage
techniques,
which
can
relieve
pain
symptoms
certain
extent,
but
cannot
solve
problem
from
root
cause.
Surgical
by
removing
herniated
pulposus,
it
more
traumatic
for
patients,
expensive
suitable
all
patients.
Therefore,
extremely
important
clarify
IVDD,
find
an
effective
convenient
further
elaborate
its
mechanism
action.
effectiveness
traditional
Chinese
medicine
in
been
well
demonstrated
clinical
medical
research.
We
have
working
herbal
formula
Duhuo
Jisheng
Decoction,
common
degenerative
disease.
Not
only
does
significant
effects,
also
few
adverse
effects.
At
present,
we
found
that
action
involves
regulation
reduction
apoptosis
pyroptosis
NPCs,
inhibition
extracellular
matrix
degradation,
improvement
intestinal
flora,
etc.
However,
relevant
articles
yet
comprehensively
systematically
summarized
mechanisms
they
exert
their
effect.
this
paper
will
explain
it.
This
great
significance
social
value
elucidating
improving
provide
theoretical
basis
scientific
with
medicine.
Journal of Orthopaedic Surgery and Research,
Journal Year:
2023,
Volume and Issue:
18(1)
Published: Aug. 14, 2023
Although
previous
studies
have
suggested
a
close
association
between
gut
microbiota
(GM)
and
intervertebral
disc
degeneration
(IVDD),
the
causal
relationship
them
remains
unclear.
Hence,
we
thoroughly
investigate
their
by
means
of
two-sample
Mendelian
randomization
(MR)
study,
aiming
to
determine
impact
on
risk
developing
degeneration.Summary
data
from
genome-wide
GM
(the
MiBioGen)
IVDD
FinnGen
biobank)
been
acquired.
The
inverse
variance
weighted
(IVW)
method
was
utilized
as
primary
MR
analysis
approach.
Weighted
median,
MR-Egger
regression,
mode,
simple
mode
were
used
supplements.
pleiotropy
residual
sum
outlier
(MR-PRESSO)
regression
performed
assess
horizontal
pleiotropy.
Cochran's
Q
test
evaluated
heterogeneity.
Leave-one-out
sensitivity
further
conducted
reliability
relationship.
A
reverse
potential
causation.We
identified
nine
microbial
taxa
that
causally
associated
with
(P
<
0.05).
Following
Benjamini-Hochberg
corrected
test,
phylum
Bacteroidetes
higher
remained
significant
(IVW
FDR-corrected
P
=
0.0365).
results
Cochrane
did
not
indicate
heterogeneity
>
Additionally,
both
intercept
MR-PRESSO
global
revealed
our
influenced
Furthermore,
leave-one-out
substantiated
In
analysis,
no
evidence
found
suggest
has
an
microbiota.Our
validate
particular
IVDD,
thus
providing
fresh
insights
into
microbiota-mediated
mechanism
laying
groundwork
for
research
targeted
preventive
measures.
Journal of Orthopaedic Surgery and Research,
Journal Year:
2024,
Volume and Issue:
19(1)
Published: Jan. 3, 2024
Abstract
Purpose
Lower
back
pain
(LBP),
mainly
caused
by
intervertebral
disk
(IVD)
degeneration
(IDD),
is
widely
prevalent
worldwide
and
a
serious
socioeconomic
burden.
Numerous
factors
may
trigger
this
degenerative
process,
microbial
dysbiosis
has
recently
been
implicated
as
one
of
the
likely
causes.
However,
exact
relationship
between
IDD
microbiome
remains
obscure.
In
study,
we
investigated
gut
microbiota
composition
fecal
metabolic
phenotype
discussed
possible
influences
on
IDD.
Methods
Fecal
DNA
was
extracted
from
16
samples
(eight
rabbit
models
with
eight
sex-
age-matched
healthy
controls)
analyzed
high-throughput
16S
rDNA
sequencing.
The
were
also
liquid
chromatography–mass
spectrometry-based
metabolomics.
Multivariate
analyses
conducted
for
omics
data
IDD,
linear
discriminant
analysis
effect
size
employed
biomarker
discovery.
Moreover,
Kyoto
Encyclopedia
Genes
Genomes
(KEGG)
database
used
to
annotate
differential
metabolites.
potential
correlation
metabolites
then
assessed.
Results
sequencing
results
showed
that
β-diversity
significantly
different
control
groups,
distinct
abundance
levels
dominant
genera.
59
upregulated
91
downregulated
in
rabbits
versus
controls.
KEGG
enrichment
revealed
top
pathways
remarkably
impacted
tyrosine
metabolism,
amino
sugar
nucleotide
benzoate
degradation,
ABC
transporters,
ascorbate
aldarate
pantothenate
CoA
biosynthesis,
pyrimidine
metabolism.
DL-tyrosine
N
-acetylmuramic
acid
associated
multiple
bacterial
genera,
including
Helicobacter
Vibrio
,
which
play
important
roles
process
IVD
degeneration.
Conclusion
Our
findings
altered
model.
metabolome
provides
deeper
understanding
its
etiopathogenesis.
These
provide
direction
theoretical
basis
clinical
application
transplantation,
probiotics,
other
methods
regulate
treatment
LBP
Neurospine,
Journal Year:
2025,
Volume and Issue:
22(1), P. 211 - 221
Published: March 31, 2025
Objective:
The
precise
mechanisms
driving
intervertebral
disc
degeneration
(IVDD)
development
remain
unclear,
but
evidence
suggests
a
significant
involvement
of
gut
microbiota
(GM)
and
blood
metabolites.
We
aimed
to
investigate
the
causal
relationships
between
GM,
IVDD,
metabolites
using
Mendelian
randomization
(MR)
analysis.Methods:
utilized
summary
statistics
GM
from
MiBioGen
consortium,
1400
genome-wide
association
studies
(GWAS)
Catalog,
IVDD
data
FinnGen
repository,
which
are
sourced
largest
GWAS
conducted
date.
Employing
bidirectional
MR
analyses,
we
investigated
IVDD.
Additionally,
2
mediation
2-step
multivariable
(MVMR),
identify
potential
mediating
metabolites.Results:
Five
bacterial
genera
were
causally
associated
with
while
did
not
show
effect
on
GM.
In
analysis,
Eubacteriumfissicatenagroup,
RuminococcaceaeUCG003,
Lachnoclostridium,
Marvinbryantia
genera,
along
X-24949,
Pimeloylcarnitine/3-methyladipoylcarnitine
(C7-DC),
X-24456,
histidine,
2-methylserine,
Phosphocholine,
N-delta-acetylornithine,
all
significantly
(all
p
<
0.05).
MVMR
analysis
revealed
that
associations
Eubacteriumfissicatenagroup
genus
mediated
by
X-24949
(8.1%,
=
0.024);
Lachnoclostridium
histidine
(18.1%,
0.013);
RuminococcaceaeUCG003
C7-DC
(-7.5%,
0.041).Conclusion:
present
study
offers
supporting
several
specific
taxa
as
well
identifying
European Spine Journal,
Journal Year:
2025,
Volume and Issue:
unknown
Published: April 21, 2025
Although
previous
studies
have
indicated
a
potential
association
between
the
gut
microbiota
and
intervertebral
disc
degeneration
(IVDD),
precise
nature
of
this
relationship
remains
unclear.
The
objective
study
is
to
further
explore
causal
IVDD
using
bidirectional
Mendelian
randomization
approach,
with
aim
identifying
microbial
characteristics
associated
IVDD.
Using
data
from
genome-wide
(GWAS)
involving
412
species
227,388
controls
29,508
cases
Inverse
variance
weighted
(IVW)
was
used
as
primary
(MR)
analysis,
complemented
by
median,
MR-Egger
regression,
mode
simple
methods.
Extensive
sensitivity
analyses
were
performed
confirm
robustness
results
assess
heterogeneity
horizontal
pleiotropy.
This
revealed
positive
genetic
predisposition
6
types
through
IVW
method,
indicating
that
increased
levels
these
may
lead
higher
risk
Conversely,
found
negative
effects
on
IVDD,
suggesting
protective
effect
against
Reverse
MR
analysis
such
possibilities
1
5
relationships
microbiota.
Cochran's
Q
test,
MR-PRESSO
all
yielded
p-values
greater
than
0.05,
there
no
significant
or
pleiotropy
in
We
approach
identify
various
Our
findings
lay
foundation
for
exploration
pathogenesis
treatment
strategies
provide
new
research
biomarkers
IVDD-related
metabolic
Frontiers in Microbiology,
Journal Year:
2024,
Volume and Issue:
15
Published: March 25, 2024
Background
Observational
studies
have
hinted
at
a
correlation
between
the
gut
microbiota
and
spinal
pain
(SP).
However,
impact
of
on
SP
remains
inconclusive.
Methods
In
this
study,
we
employed
two-sample
Mendelian
randomization
(MR)
analysis
to
explore
causal
relationship
SP,
encompassing
neck
(NP),
thoracic
spine
(TSP),
low
back
(LBP),
(BP).
The
compiled
data
originated
from
genome-wide
association
study
(GWAS)
conducted
by
MiBioGen
consortium
(
n
=
18,340).
Summary
for
NP
were
sourced
UK
Biobank,
TSP
FinnGen
LBP
both
Biobank
Biobank.
BP
obtained
primary
analytical
approach
assessing
relationships
was
Inverse
Variance
Weighted
(IVW)
method,
supplemented
various
sensitivity
analyses
ensure
result
robustness.
Results
IVW
unveiled
37
bacterial
genera
with
potential
SP.
After
Benjamini-Hochberg
corrected
test,
four
emerged
strong
Specifically,
Oxalobacter
(OR:
1.143,
95%
CI
1.061–1.232,
P
0.0004)
Tyzzerella
3
1.145,
1.059–1.238,
0.0007)
identified
as
risk
factors
LBP,
while
Ruminococcaceae
UCG011
0.859,
0.791–0.932,
0.0003)
marked
protective
factor
Olsenella
0.893,
0.839–0.951,
recognized
or/and
sciatica.
No
significant
heterogeneity
or
horizontal
pleiotropy
observed
through
alternative
testing
methods.
Conclusion
This
establishes
shedding
light
“gut-spine”
axis.
These
findings
offer
novel
perspectives
understanding
etiology
provide
theoretical
foundation
interventions
targeting
prevent
treat
The Journals of Gerontology Series A,
Journal Year:
2024,
Volume and Issue:
79(8)
Published: June 10, 2024
Abstract
Background
Nucleus
pulposus
cell
(NPC)
senescence
in
intervertebral
disc
(IVD)
tissue
is
the
major
pathological
cause
of
degeneration
(IDD).
N6-methyladenosine
(m6A)
methylation
and
gut
microbiota
play
important
roles
progression
IDD.
This
study
investigated
whether
methyltransferase-like
3
(METTL3)
regulates
TLR2
m6A
modification
to
influence
NPC
senescence.
Methods
An
IDD
rat
model
was
established
by
lumbar
IVD
puncture
NPCs
were
challenged
with
IL-1β
mimic
injury.
rats
IL-1β-exposed
treated
METTL3-interfering
lentivirus
agonist
Pam3CSK4.
Compositional
changes
analyzed
fecal
transplantation
procedures
used.
senescence,
cycle,
expression
senescence-associated
secretory
phenotype
(SASP)
factors
assessed.
The
enrichment
binding
IGF2BP1
mRNA
examined.
Results
METTL3
highly
expressed
rats.
silencing
attenuated
senescent
phenotypes
reduced
secretion
SASP
factors.
Pam3CSK4
reversed
beneficial
effects
on
stabilized
an
IGF2BP1-dependent
manner.
restored
specific
levels
rats,
which
further
administration
Fecal
from
silenced
altered
Conclusions
These
results
demonstrate
amelioration
injury,
involving
modulation
microbiota.
findings
support
as
a
potential
therapeutic
target
for
