Research Square (Research Square),
Journal Year:
2023,
Volume and Issue:
unknown
Published: Dec. 8, 2023
Abstract
Multiple
sclerosis
(MS)
is
an
autoimmune
demyelinating
disease
influenced
by
environmental
factors.
Except
during
relapses,
baseline
neurological
status
generally
stable
in
the
early
stage,
whereas
progressive
deterioration
may
occur
silently.
The
form
(secondary
MS;
SPMS)
characterised
both
neuroinflammation
and
neurodegeneration
differs
significantly
from
non-progressive
microbiome
profiles1
2
3.
After
confirming
increased
abundance
of
gut
bacterium
“Tyzzerella
nexilis”
SPMS,
role
T.nexilis
MS
was
studied.
strain-level
analysis
based
on
long-read
metagenomics
identified
a
distinct
cluster
highly
enriched
SPMS.
strains
this
novel
were
incredible
number
mobile
genetic
elements
(MGEs)
absence
defence
systems
against
MGEs.
Mono-colonisation
with
MGEs-enriched
strain
made
germ-free
mice
more
susceptible
to
induction
experimental
encephalomyelitis.
pathogenicity
mediated
TLR5
stimulation
flagella
encoded
Moreover,
thought
have
potentials
causing
neurodegeneration,
because
its
ability
produce
reduced
sulphur
compounds
Such
horizontal
gene
transfer,
functional
diversity
beyond
existing
bacterial
taxonomy,
causal
implications
chronic
disorders
microbiome.
Journal of Alzheimer s Disease,
Journal Year:
2025,
Volume and Issue:
unknown
Published: April 15, 2025
Background
Alzheimer's
disease
(AD)
is
a
debilitating
neurodegenerative
disorder.
Although
peripheral
immune
cells
have
been
implicated
in
the
pathology
of
AD,
causal
relationship
between
blood
and
AD
remains
to
be
fully
elucidated.
Objective
To
examine
association
cell
phenotypes
mediated
by
metabolite,
two-step
Mendelian
randomization
(MR)
analysis
was
performed.
Methods
Summary
statistics
were
obtained
from
two
largest
independent
cohorts.
We
explored
bidirectional
univariable
MR
explore
associations
assessed
proportion
metabolite
phenotypes.
Results
The
IgD
+
CD38-
B
(Bm1)
found
increase
risk
both
FinnGen
database
(
p
=
0.033)
UK
Biobank
0.034).
Conversely,
hematopoietic
stem
associated
with
decreased
0.045)
0.017).
Mediation
revealed
indirect
effects
Bm1
on
through
cysteine
levels
(β
5
×
10
−3
),
Acetylcarnitine
(C2)
propionylcarnitine
(C3)
ratio
4.5
Gamma-glutamyl-alpha-lysine
2.6
19.4%,
16.9%
9.6%
total
effect,
respectively.
Additionally,
influenced
Glycolithocholate
sulfate
1.5
3.5%.
Conclusions
Our
findings
demonstrate
that
impact
AD.
These
may
influence
various
identifying
potential
intervention
targets
for
individuals
at
risk.
