
A big, successful trial of probiotics - ValentineC
https://www.theatlantic.com/science/archive/2017/08/at-last-a-big-successful-trial-of-probiotics/537093/?single_page=true
======
rubidium
Here's the nature article (paywall):
[http://www.nature.com/nature/journal/vaop/ncurrent/full/natu...](http://www.nature.com/nature/journal/vaop/ncurrent/full/nature23480.html)

"The special mixture included a probiotic called Lactobacillus plantarum
ATCC-202195 combined with fructo-oligosaccharide (FOS), an oral synbiotic
preparation developed by Dr. Panigrahi." (from
[https://medicalxpress.com/news/2017-08-probiotics-sepsis-
inf...](https://medicalxpress.com/news/2017-08-probiotics-sepsis-
infants.html))

Decrease in other infections (respiratory and nasal) is particularly
interesting to see.

Now I want a HN MD to weigh in.

~~~
hanklazard
Pediatric MD PhD. These are exciting results.

Sepsis among neonates is a major concern, even in the developed world. Babies
new to the world have very weak immune systems, particularly with regard to
antibody response which is initially almost entirely composed of waning
amounts of transplacental IgA. This paper points out the the developing world
has even higher rates of infant mortality from bacterial sepsis. So this is a
big problem and impactful solutions have been tough to come by.

This is a large double-blind placebo controlled trial. They gave eligible
babies 7 consecutive daily doses of either placebo or the study agent. Table 1
shows that both study groups are very similar, so we should not be too
concerned with confounding variables. Table 2 shows the striking data re:
sepsis death rates, with this "synbiotic" (probiotic bacteria + bacterial
food) reducing death from sepsis by almost half(!). Table 3 looks at all
causes of death and importantly, significant differences in other causes of
death were not observed between the two groups--it wouldn't be all that
helpful if this synbiotic group seemed to get some other serious problem as a
side effect. It is a pretty straight-forward study and no major flaws in their
methods or conclusions jump out at me.

While exciting overall, the authors point out some important points at the
end. I think the most interesting is that they used this particular species of
lactobacillus after studying babies in India about 20 years ago and finding
differences in the rates of colonization with this and other probiotic
species. In other words, they didn't just throw any sort of "good bacteria" at
these babies--they had strong evidence to show that it actually colonized them
and therefore _could_ , in theory, have an effect on rates of sepsis. If they
had used lactobacillus GG (one of the other species that they found had low
rates of colonization), it would stand to reason that they wouldn't have
gotten such an impressive effect or maybe none at all. Then the media would
say, "probiotics don't save babies from sepsis." Basically I'm just applauding
their careful selection of this bacterial species.

One final important note is that this result should not be generalized to
other populations without future studies showing similar effects. The gut
microbiome is influenced by geography and other environmental factors and
interacts heavily with out immune systems, large parts of which vary by
genetic background. To put it another way, just because this bacterial species
works well in rural India does not mean it will work well in Peru or anywhere
else.

~~~
geomark
Outstanding comment. Thank you.

------
manmal
If you want to try L. Plantarum yourself, get the strain 299v if you can.
There's one by Jarrow (not affiliated, just made good experiences with it).
AFAIK, most other strains of L. Plantarum produce D-lactic acid, while 299v
produces L-lactic acid (I've even seen a paper where they used 299v to treat
acidosis). D-lactic acid can be hard to metabolize and can lead to acidosis.
Probiotics-induced acidosis is a thing - not good, most people with this end
up in hospital and need infusions and some kind of intervention for the long
term.

Acidophilus generally produces D-lactic acid, while e.g. L casei shirota
(Yakult) does not. It pays to take a hard look at the strains in a probiotic.

~~~
ValentineC
Just did a quick online search, and it seems that D-lactic acid might be
responsible for Chronic Fatigue Syndrome too. This is something I'm going to
read up more in the next few days.

Are there any good resources on this?

------
Ovah
I find the word probiotic to be inherently problematic. It includes any and
all microorganisms that have a single positive health benefit, whether or not
they're detrimental in other regards. That if a bacteria were to penerate gut
epithelium (very bad), it would still be a probiotic if it reduced
constupation.

Even if the research supporting the health benefits of a supplemental bacteria
is sound, a single study always has a restricted scope.

It's saddening that 'probiotics' have found their way to products such as baby
formula, while there is pretty much no regulation governing their sales and
use (at least in Europe).

~~~
macawfish
In my opinion, the word antibiotic is even more problematic.

In a recent survey, 13% of practitioners admitted to having used sedatives or
antibiotics as placebos:

[https://www.sciencedaily.com/releases/2008/10/081023195216.h...](https://www.sciencedaily.com/releases/2008/10/081023195216.htm)

To me, antibiotics are an example of dangerous superstition rearing its nasty
head right there smack in the middle an institution that prides itself as
rational and superior.

I think pre-med and med school students should be required to take courses in
chaos theory and ecology, as well as open minded primers on alternative and
preventative medicines, not so much to advocate or practice them, but so they
can have a better sense of medicine as an artform.

~~~
bitwize
Or maybe just have Jeff Goldblum tell them that they're so preoccupied with
whether they could that they didn't stop to think about whether they should.
And that life finds a way.

~~~
macawfish
Yeah they should be required to watch Jurassic Park (the original ONLY though
the new one is garbage propaganda)

------
RcouF1uZ4gsC
The 9% placebo and even the 5% treatment sepsis rate seems very high.
According to
[http://emedicine.medscape.com/article/978352-overview#a6](http://emedicine.medscape.com/article/978352-overview#a6)
the US rate of neonatal sepsis is around 2/1000 live births so around 0.2%.

Given this, I wonder how applicable these results would be to neonates in the
US.

~~~
btilly
The US generally has clean water. The third world, and India in particular,
frequently do not.

That said, the other immune boosts are interesting here. And what would be
doubly interesting is to figure out probiotics that prevent allergies.

We've known for years that a child who is exposed to real illnesses in a dirty
environment may die from that, but won't generally go on to develop asthma. In
the developed world we have a lot of health problems coming from the immune
system looking so hard for threats that it starts attacking your own body.

There is very, very good reason to believe that the right probiotics would
solve this problem. However discovering what those probiotics are is not so
simple...

~~~
emilp89
Hygiene hypothesis hasn't been proven yet.

~~~
btilly
It may not be conclusively proven, but there is strong supporting evidence.
See, for example,
[http://www.jacionline.org/article/S0091-6749(15)01193-8/abst...](http://www.jacionline.org/article/S0091-6749\(15\)01193-8/abstract).

------
culiuniversal
They initially planned to include 8000 babies, but stopped early. With only a
week of treatment they already found a significant decrease in sepsis rates.
They stopped because they thought it'd be highly unethical to deprive the
other babies of a life-saving treatment. This is a heartwarming example of
when humanity and science conflict, but I'm glad humanity won

~~~
dflock
That's standard procedure for clinical trials.

------
Mz
_Aside from preventing sepsis, it also reduced the risk of infections by both
the major groups of bacteria: the Gram-positives, by 82 percent; and the Gram-
negatives, which are harder to treat with antibiotics, by 75 percent. It even
reduced the risk of pneumonia and other infections of the airways by 34
percent. That was “completely unexpected,” says Panigrahi, and it’s the result
he’s especially excited about. It suggests that the synbiotic isn’t just
acting within the gut, but also giving the infants’ immune systems a body-wide
boost._

I don't know why they are so surprised. Given that some sources say the gut
constitutes up to 70 percent of the immune system, it should be fairly obvious
that improving gut health will have such effects.

Furthermore, you can infer a fairly direct relationship between gut health and
lung health based on what happens in the body at altitude: You start urinating
more to compensate for the thin air reducing your ability to exhale wastes.
The body starts clearing them out of the blood by shunting them to the
kidneys.

~~~
azinman2
But a single strain of bacteria can do that? I would say that’s pretty
surprising and if so a major discovery. I don’t currently have any such magic
pills that I’m taking...

------
icelancer
The trial looks to be exceptionally rigorous and the sample size is very
large. This is exciting science to say the least!

------
csr12928834
Interesting. I was skeptical of probiotics but the evidence seems to be
suggesting otherwise.

This kind of builds on meta-analyses showing that probiotic use cuts rates of
antibiotic-associated C. difficile infection.

Young children have very unstable microflora systems, so the results make
sense from that perspective also.

------
amai
I can recommend
[https://en.wikipedia.org/wiki/Lactobacillus_reuteri](https://en.wikipedia.org/wiki/Lactobacillus_reuteri)

"Similar results have been found in adults; those consuming L. reuteri daily
end up falling ill 50% less often, as measured by their decrease use of sick
leave."

------
mattparlane
Why the use of a placebo in a trial involving babies? Surely they would be
immune to any placebo effect?

~~~
Sophistifunk
The researchers and their parents won't be though.

------
Havoc
My issue isn't on the faith in probiotics side...the problem is which ones do
I buy.

It's near impossible to know you're getting the good stuff so to speak.

~~~
manmal
It really depends on what you need. I would be careful around soil based
species, and avoid D-lactic acid producers (which eliminates a whole lot of
probiotics), but apart from that you can just get what you need. E.g. if you
have a problem with histamine intolerance you could go for strains that
eat/reduce histamine. If you want better mood, you could try L Plantarum 299v
or Bifidobacterium Longum or L casei shirota.

~~~
throwawy81717
If you want to lose weight, _Christensenella minuta_ is worth examining. The
research[1,2] is preliminary, and I wouldn't trust any commercial preparations
without validation, but it is compelling.

1\.
[http://www.ctl.cornell.edu/events/celebration15/posters/Wate...](http://www.ctl.cornell.edu/events/celebration15/posters/Waters.pdf)

2\.
[http://www.cell.com/abstract/S0092-8674(14)01241-0](http://www.cell.com/abstract/S0092-8674\(14\)01241-0)

~~~
manmal
I'm intrigued by what mechanism this happens. Would be great if it changed the
"fat set point" in the hypothalamus by reducing inflammation there
([https://news.ycombinator.com/item?id=14932541](https://news.ycombinator.com/item?id=14932541)).

Last time I tried a strain from the clostridia family (butyricum) I had an
adverse reaction, so I might not be able to use this. But, everybody's
different.

------
markdown
Does yoghurt have the good stuff?

------
TheBeardKing
The study was done on newborns just starting breastfeeding, but doesn't say
whether only vaginal births or if C-sections were included.

~~~
adrice727
99.8% and 99.7% of the births were vaginal for those receiving the placebo and
the probiotics, respectively.

[https://www.nature.com/articles/nature23480.epdf](https://www.nature.com/articles/nature23480.epdf)

------
colordrops
All the products containing Lactobacillus plantarum may see a boost in sales.

~~~
uncle_d
This strain is in milk kefir, no? Easy to cultivate at home.

See also:
[http://www.bbc.co.uk/news/health-38800977](http://www.bbc.co.uk/news/health-38800977)

Water kefir is also available :)

~~~
option_greek
Anecdotal: I recently started taking Milk Kefir and it has been a life
changer. I never thought I had any problems till they were resolved by Kefir.
Seen great improvements in energy levels and anxiety. It even fixed the minor
IBS I had.

~~~
emilp89
Factory produced Kefir has very few probiotics. They were removed
intentionally. So maybe just placebo.

~~~
option_greek
I actually make it at home as Kefir isn't sold in my country :). I couldn't
yet take a call on whether its a placebo or not. My partner says its placebo
effect too but I don't think so.

------
quickthrower2
Gotta be done:

[https://xkcd.com/1471/](https://xkcd.com/1471/)

------
nikolay
I've been using General Biotics 115-strain pre- and probiotic product called
Equilibrium [1]. You can find more info in the Science section [2].

[1]:
[https://www.generalbiotics.com/orders/new/](https://www.generalbiotics.com/orders/new/)

[2]:
[https://www.generalbiotics.com/science/](https://www.generalbiotics.com/science/)

~~~
skypather
But 115-strain is not the strain mentioned in this study, isn't it? So your
point of bringing up this product is??!! I meant, isn't one major point of
this study is "not all probiotics are the same and finally someone found one
is actually very helpful to new born babies"?

