bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2023,
Номер
unknown
Опубликована: Март 17, 2023
ABSTRACT
Background
Fecal
microbiota
transplantation
(FMT)
and
fecal
virome
(FVT,
sterile
filtrated
donor
feces)
have
been
effective
in
treating
recurrent
Clostridioides
difficile
infections,
possibly
through
bacteriophage-mediated
modulation
of
the
gut
microbiome.
However,
challenges
like
variability,
costly
screening,
coupled
with
concerns
over
pathogen
transfer
(incl.
eukaryotic
viruses)
FMT
or
FVT
hinders
their
wider
clinical
application
less
acute
diseases.
Methods
To
overcome
these
challenges,
we
developed
methods
to
broaden
FVT’s
while
maintaining
efficacy
increasing
safety.
Specifically,
employed
following
approaches:
1)
Chemostat-fermentation
reproduce
bacteriophage
component
remove
viruses
(FVT-ChP),
2)
solvent-detergent
treatment
inactivate
enveloped
(FVT-SDT),
3)
pyronin-Y
inhibit
RNA-virus
replication
(FVT-PyT).
We
assessed
processed
FVTs
a
C.
infection
mouse
model
compared
them
untreated
(FVT-UnT),
FMT,
saline.
Results
FVT-SDT,
FVT-UnT,
FVT-ChP
reduced
incidence
mice
reaching
humane
endpoint
(0/8,
2/7,
3/8,
respectively)
FVT-PyT,
saline
control
(5/8,
7/8,
5/7,
significantly
load
colonizing
cells
toxin
A/B
levels.
There
was
potential
elimination
colonization,
7
out
8
treated
FVT-SDT
testing
negative
qPCR.
In
contrast,
all
other
treatments
exhibited
continued
presence
.
Moreover,
results
were
supported
by
changes
microbiome
profiles,
cecal
cytokine
levels
histopathological
findings.
Assessment
viral
engraftment
FMT/FVT
host-phage
correlations
analysis
suggested
that
phages
likely
an
important
contributing
factor
associated
efficacy.
Conclusions
This
proof-of-concept
study
show
specific
modifications
hold
promise
addressing
related
variability
risks.
Two
strategies
lead
limiting
colonization
mice,
solvent/detergent
chemostat-propagation
emerging
as
promising
approaches.
Neurobiology of Stress,
Год журнала:
2024,
Номер
30, С. 100629 - 100629
Опубликована: Март 18, 2024
In
recent
years,
an
increasing
attention
has
given
to
the
intricate
and
diverse
connection
of
microorganisms
residing
in
our
gut
their
impact
on
brain
health
central
nervous
system
disease.
There
been
a
shift
mindset
understand
that
drug
addiction
is
not
merely
condition
affects
brain,
it
now
being
recognized
as
disorder
also
involves
external
factors
such
intestinal
microbiota,
which
could
influence
vulnerability
development
addictive
behaviors.
Furthermore,
stress
social
interactions,
are
closely
linked
powerful
modulators
addiction.
This
review
delves
into
mechanisms
through
microbiota-stress-immune
axis
may
shape
work
integrates
preclinical
clinical
evidence
demonstrate
bidirectional
communication
between
stress,
behaviors,
substance
use
disorders
suggesting
microbes
might
modulate
having
significance
Abstract
Background
Fecal
microbiota
transplantation
(FMT)
and
fecal
virome
(FVT,
sterile
filtrated
donor
feces)
have
been
effective
in
treating
recurrent
Clostridioides
difficile
infections,
possibly
through
bacteriophage-mediated
modulation
of
the
gut
microbiome.
However,
challenges
like
variability,
costly
screening,
coupled
with
concerns
over
pathogen
transfer
(incl.
eukaryotic
viruses)
FMT
or
FVT
hinder
their
wider
clinical
application
less
acute
diseases.
Methods
To
overcome
these
challenges,
we
developed
methods
to
broaden
FVT’s
while
maintaining
efficacy
increasing
safety.
Specifically,
employed
following
approaches:
(1)
chemostat-fermentation
reproduce
bacteriophage
component
remove
viruses
(FVT-ChP),
(2)
solvent-detergent
treatment
inactivate
enveloped
(FVT-SDT),
(3)
pyronin-Y
inhibit
RNA
virus
replication
(FVT-PyT).
We
assessed
processed
FVTs
a
C.
infection
mouse
model
compared
them
untreated
(FVT-UnT),
FMT,
saline.
Results
FVT-SDT,
FVT-UnT,
FVT-ChP
reduced
incidence
mice
reaching
humane
endpoint
(0/8,
2/7,
3/8,
respectively)
FVT-PyT,
saline
(5/8,
7/8,
5/7,
significantly
load
colonizing
cells
associated
toxin
A/B
levels.
There
was
potential
elimination
colonization,
seven
out
eight
treated
FVT-SDT
testing
negative
qPCR.
In
contrast,
all
other
treatments
exhibited
continued
presence
.
Moreover,
results
were
supported
by
changes
microbiome
profiles,
cecal
cytokine
levels,
histopathological
findings.
Assessment
viral
engraftment
FMT/FVT
host-phage
correlations
analysis
suggested
that
phages
likely
an
important
contributing
factor
efficacy.
Conclusions
This
proof-of-concept
study
shows
specific
modifications
hold
promise
addressing
related
variability
risks.
Two
strategies
lead
limiting
colonization
mice,
solvent/detergent
chemostat
propagation
emerging
as
promising
approaches.
Modern
habits
are
becoming
more
and
disruptive
to
health.
As
our
days
often
filled
with
circadian
disruption
stress
exposures,
we
need
understand
how
responses
these
external
stimuli
shaped
their
mediators
can
be
targeted
promote
A
growing
body
of
research
demonstrates
the
role
gut
microbiota
in
influencing
brain
function
behavior.
The
response
rhythms,
which
essential
maintaining
appropriate
environment,
known
impacted
by
microbiota.
Gut
microbes
have
been
shown
alter
host's
modulate
rhythmicity.
Although
studies
demonstrated
strong
links
between
microbiota,
rhythms
response,
such
were
conducted
an
independent
manner
not
conducive
understanding
interface
factors.
Due
interconnected
nature
this
review
explore
may
play
a
regulating
integration
signals
mammals
consequences
for
health
disease.
Neurobiology of Stress,
Год журнала:
2024,
Номер
33, С. 100686 - 100686
Опубликована: Ноя. 1, 2024
Alterations
in
gut-brain
axis
communication
pathways
and
the
gut
microbiota
ecosystem
caused
by
early
life
stress
have
been
extensively
described
as
critical
players
pathophysiology
of
stress-induced
disorders.
However,
extent
to
which
alterations
manifest
contribute
sex-specific
susceptibility
distinct
phenotypes
adulthood
has
yet
be
defined.
PeerJ,
Год журнала:
2025,
Номер
13, С. e18785 - e18785
Опубликована: Янв. 14, 2025
The
virome,
composed
of
viruses
inhabiting
diverse
ecosystems,
significantly
influences
microbial
community
dynamics
and
host
health.
phenol-chloroform
DNA
extraction
protocol
for
viromes,
though
effective,
is
time-intensive
requires
the
use
multiple
toxic
chemicals.
This
study
introduces
a
streamlined,
scalable
using
commercially-available
kit
as
an
alternative,
assessing
its
performance
against
method
across
human
fecal,
mouse
soil
samples.
No
significant
differences
in
virome
diversity
or
composition
were
seen
between
methods.
Most
viral
operational
taxonomic
units
(vOTUs)
common
to
both
methods,
with
only
small
percentage
unique
either
approach.
Alpha-
beta-diversity
analyses
showed
no
impact
on
composition,
confirming
kit’s
efficacy
versatility
sample
types
beyond
those
officially
supported
by
manufacturer.
While
approach
offers
benefits
like
reduced
toxicity
increased
throughput,
it
has
limitations
such
higher
costs
potential
issues
reliably
capturing
low-abundance
taxa.
provides
viable
option
large-scale
studies,
although
may
still
be
preferable
specific
types.
Journal of Bacteriology,
Год журнала:
2025,
Номер
unknown
Опубликована: Янв. 23, 2025
ABSTRACT
The
mammalian
gut
microbiome
is
a
dense
and
diverse
community
of
microorganisms
that
reside
in
the
distal
gastrointestinal
tract.
In
recent
decades,
bacterial
members
have
been
subject
intense
research.
Less
well
studied
large
bacteriophages
gut,
which
number
billions
viral
particles
per
gram
feces,
consist
considerable
unknown
“dark
matter.”
This
gut-residing
bacteriophages,
called
“phageome,”
plays
central
role
through
predation
transformation
native
bacteria,
interactions
with
their
hosts.
this
review,
we
will
summarize
what
known
about
composition
origins
phageome,
as
its
homeostasis
host
health.
Furthermore,
outline
phages
hosts,
plot
course
for
mechanistic
study
these
systems.