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URI Microbial metabolite repairs liver injury by restoring hepatic lipid metabolism
hinkley wrote 3 hours 33 min ago:
It seems that the powers that be decided lactobacillus was getting a
bit crowded and decided to split it into separate genuses.
From the article we are talking about [1] and itâs apparently the
most common fermenting bacteria for silage, and shows up in sauerkraut
and kimchi. [2] is another interesting one that got split into a
separate genus. No direct action has so far been found for this genus
of bacteria, but it makes the GI tract more hospitable for a large
number of probiotic species and less hospitable for others like C.
difficile, which is one of the nastiest post-antibiotic infections one
can get. So nasty it has the French word for âdifficultâ in its
name.
Found in cheddar cheese and yogurt. Any time I have problems or have to
take antibiotics I make sure to line up some of both for recovery.
URI [1]: https://en.wikipedia.org/wiki/Lactiplantibacillus_plantarum
URI [2]: https://en.wikipedia.org/wiki/Lacticaseibacillus_casei
lr4444lr wrote 3 hours 3 min ago:
Makes me wonder how much of the positive research on fermented foods
generally has to do with liver function improvement, since the organ
is crucial to the health of most of the body.
0cf8612b2e1e wrote 2 hours 34 min ago:
Koreans live off of fermented kimchi, something like 80+ pounds per
person every year. Do Koreans have lower incidence of gut
complications?
ginko wrote 54 min ago:
They have a much higher stomach cancer rate.
astrange wrote 26 min ago:
They also drink like fish and eat hot foods. Both of those are
known contributors.
hungmung wrote 2 hours 29 min ago:
I bet they've got lower rates of hep than America, but that
probably doesn't have anything to do with the kimchi.
hinkley wrote 2 hours 51 min ago:
Weâve mostly studied gut health. Something about modern diets is
messing that up substantially. Some think it may be Roundup, others
dish detergent, others some microbe we canât culture on Petri
dishes.
Llamamoe wrote 1 hour 12 min ago:
Why assume it's the diets rather than antibiotics? Your gut
microbiome develops during the first ~3y of life(including
partial heritability from your mother), after which the total set
of microbes in it remains approximately constant throughout your
life, with only the relative proportions of them shifting with
diet changes.
In contrast, antibiotics often kill a strain of a few off
completely, while suppressing everything else except for a few
strains that resist the antibiotic, which also creates a massive
opportunity for new bacteria to colonize. And these deficits are
partially heritable.
griffzhowl wrote 2 hours 33 min ago:
What's the evidence that modern diets are substantially messing
up gut health? (just curious, not (necessarily;) sceptical)
hinkley wrote 2 hours 30 min ago:
The incidence of crohnâs, IBD, celiac, etc going on out
there. Some people want to throw obesity into that ring as
well. Inflammation certainly causes weight gain.
griffzhowl wrote 2 hours 4 min ago:
Ah ok, well, obesity incidence is probably almost entirely
explained by the amount of sugar and fats in modern diets. I
wouldn't have thought of it as pertaining to gut health
specifically, but no doubt there can be relationships there.
The other things seem more plausible. Purely anecdotally, my
step-dad always thought he was intolerant to gluten because
of his reactions to British bread, but when he spent a lot of
time in France and tried bread there, he was fine.
Could be there's something about the production process of
the standard British "Chorleywood loaf" that aggravates some
bowels. [1] In general, I find it quite easy to believe that
a lot of mass-produced foods contain what are essentially
poisons, but I'm curious about evidential links (and I'm also
aware that lots of naturally-occurring foods can be poisons
if eaten too much, but that's a different question)
URI [1]: https://en.wikipedia.org/wiki/Chorleywood_bread_proc...
astrange wrote 13 min ago:
> Ah ok, well, obesity incidence is probably almost
entirely explained by the amount of sugar and fats in
modern diets.
The obesity epidemic started rapidly around 1980, but it's
unlikely diet changed for the worse since then.
Also, it happened to lab animals and pets as well. [1]
Also, it appears to be correlated with low altitudes and
interventions that cause you to move to higher altitudes
cause weight loss. [2] > Purely anecdotally, my step-dad
always thought he was intolerant to gluten because of his
reactions to British bread, but when he spent a lot of time
in France and tried bread there, he was fine.
The American equivalent of this (people who go to Europe
and think the bread is healthier because it's easy to
digest) is because we fortify wheat and the extra nutrients
esp. iron cause stomach discomfort.
URI [1]: https://royalsocietypublishing.org/doi/abs/10.1098...
URI [2]: https://journals.plos.org/plosone/article?id=10.13...
XorNot wrote 1 hour 46 min ago:
You need to define "spent some time". Was he working? On
sabbatical or holiday?
"I travelled somewhere and things improved" has the serious
complication that you changed almost everything at once and
possibly removed major stress sources. You were even
outside of your own home - and buildings have ecosystems
themselves anyway as well as just systemic faults.
griffzhowl wrote 1 hour 32 min ago:
Yeah ok, but it's just an anecdote so it doesn't count as
generalisable evidence in any case.
I would just add that when he got back to Britain and
tried baguette style bread there he found that he could
tolerate it in Britain too.
Again, I'm just reporting a story as it was told to me
because I was reminded of it in response to the previous
comment.
DaveZale wrote 1 hour 50 min ago:
I believe that ultraprocessed foods are recognized as
borderline poisons. Esp if they contain trans fats or
hydrogenated fats, which arw described as "slow acting
poisons" - but the same goes for "extruded foods" - stuff
that is processed to the point where it can be molded or
squeezed into funny looking shapes.
wdwvt1 wrote 4 hours 53 min ago:
There are so many interesting metabolites that the gut microbiome
produces that modulate the immune system. My former startup (Interface
Biosciences) was trying to develop a process for identifying and
developing these as traditional pharmaceuticals (e.g. small molecule
drugs).
One of the big problems with most of these metabolites is that they
work better in preventing the emergence of disease pathology than they
do in ameliorating it. In other words, they aren't super reverse causal
for disease. You'll note that in this study, the design was
pretreatment with the beneficial metabolite to prevent injury, rather
than rescue once injury occurred ([0], [1]).
It's difficult to make a prophylactic pharmaceutical/intervention - the
market is smaller, the therapeutic index must be larger, and the
insurance reimbursement is harder to get. I hope that someone smarter
can break this open at some point. Natural products are the source of
over 50% of approved drugs (though weighted heavily towards
antibiotics), and the gut microbiome has really not been explored
enough for its natural products.
As a note on the probiotics - be very skeptical of probiotic claims.
Even if the microbe actually engrafts in your GI tract (a very big if),
the probability that it is producing a given 'good' metabolite is
unclear. Microbes have thousands of genes and they are constantly
changing metabolism (=the metabolites they excrete) as a function of an
innumerable array of factors including: energetic (what food sources
are in the GI at that moment?), competitive (what competitor species
are they sensing?), immune (what is the host immune state?), and
physical (do I sense a high diffusion environment?) factors.
[0] From the abstract: "Here, we report that oral administration of
10-HSA prevented AFB1-induced gut epithelial barrier disruption and
preserved mucosal T cell populations.
[1] From the methods: "Mice were randomly assigned into three groups.
One group (n = 6) was pretreated with 10-HSA (AstaTech A10837) at 100
mg/kg/day in vehicle for one week and then aflatoxin-β1 (Sigma-Aldrich
A6636) dissolved in DMSO (final concentration in water was 0.1%) was
added to their drinking water for 21 days at a concentration of 5 mg/L.
Another group (n = 6) was pretreated with the vehicle control for 1
week and then aflatoxin-β1 was added to their drinking water for 21
days at a concentration of 5 mg/L. The third group (n = 4) served as
the negative control group and received vehicle for 1 week prior to
DMSO addition to drinking water for 21 days.
ck2 wrote 5 hours 37 min ago:
10-HSA is a fatty-acid metabolite produced by Lactobacillus bacteria
Lactobacillus Plantarum is a super common probiotic that produces
10-HSA and other important metabolites
its commercial name is also known as lp299v which has been studied for
decades, tons of studies
for example: [1] lp299v is extreme safe and can be taken in mega-doses
however it will not colonize in the GI so would have to be taken
routinely
URI [1]: https://www.mdpi.com/2073-4344/10/2/154
0cf8612b2e1e wrote 2 hours 43 min ago:
Wouldnât it be easier to just take a gram of the metabolite itself
vs hoping for long term colonization?
DaveZale wrote 1 hour 56 min ago:
yes, this is what's done with tributyrin which is a triester of
butyric acid. You want to ingest either a butyric acid salt or an
ester of butyric acid, since the butyric acid itself is really
stinky.
mmmpetrichor wrote 7 hours 55 min ago:
I'll drink to that!
verst wrote 1 hour 49 min ago:
Makes me wonder whether Makgeolli (a low alcohol fermented
traditional Korean beverage) contains this too.
DaveZale wrote 1 hour 49 min ago:
Sure, or kombucha?
DaveZale wrote 6 hours 3 min ago:
kefir has that microbe. So drink some kefir
and eat a kraut dog. Or a Ruben.
URI [1]: https://en.m.wikipedia.org/wiki/Lactiplantibacillus_plantaru...
searine wrote 8 hours 41 min ago:
Supported by grants from NIH/NIAID Grants and the University of
California Davis.
DaveZale wrote 5 hours 59 min ago:
yeah Davis is agriculturally oriented. Because this microbe grows in
cows stomachs it is added to silage (feed) - so dairy products have
this metabolite.
Amazing finding. The statistics on liver damage from aflatoxins said
to affect potentially 5 billion people. And of course in the US,
with its high incidence of obesity has liver issues due to NAFLD.
Then of course the heavy drinkers are all at risk.
toomuchtodo wrote 4 hours 3 min ago:
URI [1]: https://www.fda.gov/news-events/press-announcements/fda-ap...
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