Gut dysbiosis was inevitable, but tolerance was not: temporal responses of the murine microbiota that maintain its capacity for butyrate production correlate with sustained antinociception to chronic morphine
Gut Microbes,
Год журнала:
2025,
Номер
17(1)
Опубликована: Янв. 12, 2025
The
therapeutic
benefits
of
opioids
are
compromised
by
the
development
analgesic
tolerance,
which
necessitates
higher
dosing
for
pain
management
thereby
increasing
liability
drug
dependence
and
addiction.
Rodent
models
indicate
opposing
roles
gut
microbiota
in
tolerance:
morphine-induced
dysbiosis
exacerbates
whereas
probiotics
ameliorate
tolerance.
Not
all
individuals
develop
could
be
influenced
differences
microbiota,
yet
no
study
design
has
capitalized
upon
this
natural
variation.
We
leveraged
behavioral
variation
a
murine
model
voluntary
oral
morphine
self-administration
to
elucidate
mechanisms
influences
Although
mice
shared
similar
morphine-driven
changes
that
largely
masked
informative
associations
with
variability
our
high-resolution
temporal
analyses
revealed
divergence
progression
best
explained
sustained
antinociception.
Mice
did
not
tolerance
maintained
capacity
production
short-chain
fatty
acid
(SCFA)
butyrate
known
bolster
intestinal
barriers
promote
neuronal
homeostasis.
Both
fecal
microbial
transplantation
(FMT)
from
donor
dietary
supplementation
significantly
reduced
independently
suppression
systemic
inflammation.
These
findings
inform
immediate
therapies
extend
efficacy
opioids.
Язык: Английский
Self-Organizing Assembloids Reveal Enteric Nervous System Dynamics in Gut Homeostasis and Regeneration
Ilke Sari,
Baki Uzun,
Melda O. Oguz
и другие.
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2025,
Номер
unknown
Опубликована: Янв. 14, 2025
The
enteric
nervous
system
(ENS)
is
essential
for
intestinal
health,
exhibiting
adaptability
to
environmental
and
physiological
challenges.
However,
the
mechanisms
underlying
ENS
plasticity
resilience
remain
poorly
understood.
Organoid
technology
has
revolutionized
in
vitro
modeling
by
accurately
replicating
epithelial
structures
enabling
significant
advancements
understanding
gastrointestinal
biology.
traditional
organoids
are
limited
their
ability
study
ENS,
as
they
lack
multicellular
composition
functional
architecture
necessary
model
complex
interactions
between
neurons,
glia,
mesenchymal,
smooth
muscle,
cells.
To
address
these
limitations,
we
developed
murine
ENS-Rich
Assembloids
(ERAs)
that
self-organize
replicate
cellular
diversity,
including
structure,
of
native
colonic
tissue.
These
assembloids
recreate
neuron-glia
interactions,
reflect
regenerative
processes,
provide
a
novel
platform
studying
dynamics
under
controlled
conditions.
Integrating
findings
from
an
vivo
model,
demonstrate
inflammation
induces
coordinated
reorganization
S100b+
glial
cells,
TUJ1+
PDGFRA+
mesenchymal
revealing
conserved
plasticity.
We
identify
pleiotrophin
(PTN)
signaling
via
Protein
Tyrosine
Phosphatase
Receptor
Type
Z1
(PTPRZ1)
key
pathway
facilitating
neural
elongation
enhancing
interactions.
Moreover,
show
activated
neurons
transfer
lipids
support
mechanism
during
inflammation.
position
glia
protective
hubs
fostering
tissue
regeneration.
By
building
on
foundational
success
organoid
addressing
its
limitations
ENS-rich
establish
transformative
tool
investigating
responses
disease,
repair.
Язык: Английский
mpactR: an R adaptation of the metabolomics peak analysis computational tool (MPACT) for use in reproducible data analysis pipelines
Microbiology Resource Announcements,
Год журнала:
2025,
Номер
unknown
Опубликована: Янв. 15, 2025
mpactR
automates
pre-processing
of
liquid
chromatography-tandem
mass
spectrometry
(LC-MS/MS)
data
from
microbiological
samples
to
correct
mispicked
peaks,
resolve
inter-sample
variation
in
abundance
across
technical
replicates,
account
for
in-source
ion
fragmentation,
and
remove
background
noise
yield
high-quality
features.
The
package
is
available
through
CRAN
GitHub.
Язык: Английский
Fecal microbiota and metabolite composition associates with stool consistency in young children
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Июнь 9, 2024
ABSTRACT
Stool
consistency
explains
a
large
proportion
of
inter-individual
variation
in
gut
microbiota
and
represents
useful
measure
transit
time,
which
is
pivotal
for
bacterial
metabolism
vice
versa
.
However,
infants
small
children,
detailed
understanding
how
the
metabolome
associate
with
stool
lacking.
We
analyzed
both
2.5
(n=360),
6
(n=229),
14
(n=274),
30-month-old
children
(n=169)
from
FinnBrain
Birth
Cohort
Study
using
16s
rRNA
sequencing
mass
spectrometry-based
targeted
techniques.
used
water
content
parent-reported
as
proxies
consistency.
found
that
community
composition
well
relative
abundance
specific
genera
such
Clostridium
,
Hungatella
Lactobacillus
were
associated
Of
metabolites,
lower
concentrations
conjugated
bile
acids
acetic
acid
having
constipation
content.
Branched
short-chain
fatty
negatively
The
findings
reflect
shift
saccharolytic
to
proteolytic
gut.
Parental
crude
reports
agreed
objective
child
consistency,
similar
features
metabolome.
Overall,
our
support
concept
total
metabolic
activity
young
children.
Язык: Английский
T cells regulate intestinal motility and shape enteric neuronal responses to intestinal microbiota
Gut Microbes,
Год журнала:
2024,
Номер
17(1)
Опубликована: Дек. 20, 2024
How
the
gut
microbiota
and
immune
system
maintain
intestinal
homeostasis
in
concert
with
enteric
nervous
(ENS)
remains
incompletely
understood.
To
address
this
gap,
we
assessed
small
transit,
neuronal
density,
neurogenesis,
microbiota,
cell
populations
cytokines
wildtype
T-cell
deficient
germ-free
mice
colonized
specific
pathogen-free
(SPF)
conventionally
raised
SPF
segmented
filamentous
bacteria
(SFB)-monocolonized
mice.
increased
transit
a
T
cell-dependent
manner.
density
myenteric
submucosal
plexuses
of
ileum
colon,
similar
to
mice,
independently
cells.
SFB
manner,
but
cells
colon.
stimulated
neurogenesis
(Sox2
expression
neurons)
colon
effect
was
cell-independent.
regulated
nestin
ENS.
colonization
Th17
cells,
RORγT+
Treg
IL-1β
IL-17A
levels
By
neutralizing
IL-17A,
observed
that
they
control
microbiota-mediated
were
not
involved
regulation
motility.
Together,
these
findings
provide
new
insights
into
microbiota-neuroimmune
dialog
regulates
physiology.
Язык: Английский
Gut dysbiosis was inevitable, but tolerance was not: temporal responses of the murine microbiota that maintain its capacity for butyrate production correlate with sustained antinociception to chronic voluntary morphine
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Апрель 17, 2024
The
therapeutic
benefits
of
opioids
are
compromised
by
the
development
analgesic
tolerance,
which
necessitates
higher
dosing
for
pain
management
thereby
increasing
liability
dependence
and
addiction.
Rodent
models
indicate
opposing
roles
gut
microbiota
in
tolerance:
morphine-induced
dysbiosis
exacerbates
whereas
probiotics
ameliorate
tolerance.
Not
all
individuals
develop
tolerance
could
be
influenced
differences
microbiota,
yet
no
study
has
capitalized
upon
this
natural
variation
to
identify
specific
features
linked
We
leveraged
a
murine
model
voluntary
oral
morphine
self-administration
elucidate
mechanisms
influences
Although
mice
shared
similar
predictive
morphine-driven
changes
that
largely
masked
informative
associations
with
variability
our
high-resolution
temporal
analyses
revealed
divergence
progression
best
explained
Mice
did
not
also
maintained
abundance
taxa
capable
producing
short-chain
fatty
acid
(SCFA)
butyrate,
known
bolster
intestinal
barriers,
suppress
inflammation,
promote
neuronal
homeostasis.
Furthermore,
dietary
butyrate
supplementation
significantly
reduced
These
findings
inform
immediate
therapies
extend
efficacy
opioids.
Язык: Английский
T cells regulate intestinal motility and shape enteric neuronal responses to intestinal microbiota.
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Май 24, 2024
Abstract
The
gut
microbiota
and
immune
system
maintain
intestinal
homeostasis
regulate
physiology
in
concert
with
the
enteric
nervous
(ENS).
However,
underlying
mechanisms
remain
incompletely
understood.
Using
wildtype
T-cell
deficient
germ-free
mice
colonized
segmented
filamentous
bacteria
(SFB)
or
specific
pathogen-free
(SPF)
microbiota,
we
studied
regulation
of
ENS
motility.
Colonization
markedly
increased
Th17
cells
Treg
expressing
RORγ
+
T
both
ileum
colon
mice.
were
necessary
for
normalization
motility
after
colonization
by
SPF
SFB
to
restore
neuronal
density
also
required
neurogenic
responses
myenteric
neurons
ileum,
but
not
colon,
regulating
levels
nestin
expression.
cytokines
IL-1β
IL-17A
mediate
response
an
involved
Together,
our
findings
provide
new
insights
into
microbiota-neuroimmune
dialogue
that
regulates
physiology.
Язык: Английский
CHANGES IN THE STRUCTURE OF THE COLON WALL TISSUES UNDERTHE INFLUENCE OF BIOLOGICALLY ACTIVE SUBSTANCES
Bulletin of Taras Shevchenko National University of Kyiv Series Biology,
Год журнала:
2024,
Номер
99(4), С. 27 - 33
Опубликована: Янв. 1, 2024
Background.
The
regulation
of
the
motor
function
colon
is
carried
out
due
to
complex
combined
influence
a
endogenous
nervous
and
humoral
factors,
which
serve
as
modulators
contractile
activity
muscles
intestinal
wall.
However,
issue
use
safety
exogenous
correctors
remains
extremely
relevant
in
demand.
Thus,
search
for
potential
factors
capable
physiologically
modulating
intestines
kind
challenge
modern
scientists,
study
features
these
substances
on
tissues
wall
scientific
practical
problem
biological
science.
aim
work
was
establish
morphological
changes
structures
under
biologically
active
substances.
Methods.
conducted
94
sexually
mature
outbred
male
rats.
effect
histological
structure
sigmoid
following
studied:
quercetin,
caffeine,
floccalin,
phoridone,
mixture
floccalin
E510.
Rat
preparations
were
incubated
solutions
30
minutes
vitro,
after
examination
performed.
Intestinal
fragments
fixed
10%
neutral
formalin,
passed
through
ascending
concentrations
ethyl
alcohol,
then
embedded
paraffin.
Sections
5-7
μm
thick
made
from
obtained
paraffin
samples,
stained
with
hematoxylin
eosin.
Morphological
assessed
using
microscope.
Results.
absence
pathological
their
mixture,
also
quercetin
caffeine
recorded.
This
suggests
that
do
not
have
harmful
side
effects
relation
histostructures
E510
leads
appearance
signs
lymphocytic
infiltration,
modification
lymphoid
follicles,
loosening
swelling
submucosal
base
impaired
capillary
barrier
function.
Conclusions.
action
all
studied
substances,
exception
E510,
causes
minor
structural
or
functional
wall,
are
reactive
reversible
nature
lead
development
irreversible
phenomena.
In
contrast,
adverse
morphofunctional
requires
further
in-depth
study.
Язык: Английский