

There is no 'healthy' microbiome - roye
http://www.nytimes.com/2014/11/02/opinion/sunday/there-is-no-healthy-microbiome.html?_r=0

======
harshreality
The author seems to get carried away, emphasizing that microbiomes (measured
by host health) do not form a totally ordered set. I think that's a caricature
of what microbiome hackers are claiming. A totally ordered set would mean
there's one "best" microbiome. But there might be one or only a few "best"
microbiomes for a particular person with a particular diet.

In one section, the author criticizes microbiome hacking based on the fact
that the experimenter does't have c. difficile. Does the author really believe
that c. difficile, or other acute health problems, are the only possible
results of an unhealthy microbiome?

It seems most plausible that dietary health is going to be a function
health(microbiome, diet/environment, genetics). I doubt anyone thinks it will
be a simple function, but along with acutely unhealthy microbiomes, there will
be some obvious (given enough long-term data) problematic microbiomes across
wide genetic and dietary variations, that don't quickly cause acute disease.
And I don't think there will be as much variation as the author believes in
healthy microbiomes once you start controlling for genetics and diets.

~~~
aroch
>microbiome hackers

I really wish this wasn't a thing. I'm getting tired of all the "startups" in
my field (microbio) who are pushing microbiome-based treatments. They're not
currently regulated by the FDA and they are downright dangerous. The healthy
gut is primarily made up of (~90%) Firmicutes, Bacteroidetes, and Clostridium
of which the majority are uncultured, unsequenced and completely unstudied.
Shifting the balance a little too much one way or another can potentially
cause symptoms of Autism Spectrum Disorder. There are at least two startups in
stealthmode that I know of that are pushing microbiome matching between
"healthy" donors and "unhealthy" recipients -- very much like snake oil
salesmen. One person's healthy is another's unhealthy but these groups and
their VCs apparently don't give a shit (VC funding in science is a while other
can of worms).

If you want to be a microbiome hacker, go contribute YOUR microbiome to
_publicly funded by you_ research. I suggest the American Gut Project[1][2]
for people in the US and British Gut[3] for those in the UK and EU. For $99
you can learn about your microbiome and contribute to largest, most successful
crowdfunded research in the world. This project is _entirely_ supported by
people like you and me, directly.

[1]
[http://humanfoodproject.com/americangut/](http://humanfoodproject.com/americangut/)

[2]
[https://fundrazr.com/campaigns/4Tqx5](https://fundrazr.com/campaigns/4Tqx5)

[3]
[https://fundrazr.com/campaigns/4sSf3/ab/5qJ7f](https://fundrazr.com/campaigns/4sSf3/ab/5qJ7f)

~~~
krrrh
How do you think ubiome.com compares with these efforts? I did an analysis
with them and feel like I got some insights, but I also felt that the way the
data Is currently presented could lead to a lot of false conclusions,
especially for people without a microbiology or statistical background.

I'm also curious about your statement about how many strains are unsewurnced
and unstudied. I've read this elsewhere, and it makes me wonder if the species
% data presented by ubiome is presented with false precision.

~~~
aroch
µBiome is vapid consumerism in my opinion. They don't contribute data to the
research community (as far as I know).

The vast, vast majority of all bacteria are not culturable in a lab. That
being said, we use rRNA/rDNA sequencing[1] to build phylogenies based off of
BLAST E-values[2], or how likely it is two sequences evolved separately from
each other. We have cultured and sequenced enough of the big three (and many
of the top 100 gut microbes) that we can be statistically sure that they're
related. We can't say for sure two different but closely related sequences are
two different, closely related species but we can say they're related OTUs[3]

[1] [http://greengenes.lbl.gov/cgi-bin/nph-
index.cgi](http://greengenes.lbl.gov/cgi-bin/nph-index.cgi)

[2]
[http://www.ncbi.nlm.nih.gov/blast/Blast.cgi?CMD=Web&PAGE_TYP...](http://www.ncbi.nlm.nih.gov/blast/Blast.cgi?CMD=Web&PAGE_TYPE=BlastDocs&DOC_TYPE=FAQ#expect)

[3]
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1609233/](http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1609233/)

------
JenniferRM
The linked author doesn't seem to have a clear thesis statement, but from the
examples given (the Hadza and the Conquistadors) it appears the thesis
statement could be something like this: "Each isolated ancient human community
already has basically optimized microbiomes. In each such human niche, their
traditional microbes can probably survive in that niche. Also, those same
microbes will have been surviving for so long that second order optimizations
(like ethnic genetic adaptation to the potentially harmful parts of their
traditional microbiome package) have likely occurred. In the face of such
'bio-traditions', and their presumptively functional state, we should tread
carefully, and study everything before we muck about too much."

This seems to me like an excellent argument for why people who grew up on
family farms, or in jungles, or other vaguely historical places should not
muck about too much with their microbiomes. Heck, even third generation New
Yorkers are probably solid.

However, it seems to miss the point that urbanization, immigration, antibiotic
use, and radically weird diets (to name a few factors) are happening all over
the modern world.

Given the modern situation, having already been disrupted by biologically
unprecedented events for centuries, it seems plausible that at least some of
us are like sailors at sea, with the metaphorical equivalent of scurvy-before-
its-etiology-was-determined.

Just as, _if you have scurvy_ , it doesn't cost much to try eating citrus and
see if it helps, it seems that for people who are already unhappy with their
gut health, it probably doesn't cost much to experiment here.

If you can already see that your digestion/mood/hunger is funky by comparing
it do to friends and family, and you can read the research on that suggests
these processes can be affected by microbiomes, it seems plausible to me that
checking out uBiome or General Biotics or one of the "dating websites for
poop" (or whatever, I'm sure there are more of these things floating around)
it doesn't seem _that_ crazy to me. A bit crazy, yes. But way less crazy than
the same experimentation would be for someone who is eating and living in the
same manner as their mother's mother, and has no more tummy troubles than any
of their grandparents.

I've published a little in this area, and I didn't know about the conquistador
story, so the article was appreciated, but I'm also personally a fan of
experimentation that is early, fast, and cheap and I didn't see any of the
experimental cost benefit analysis that could have been there, and could have
made the article better.

------
abandonliberty
The article gives a lot of neat background, but primarily deconstructs a straw
man argument.

He does a pretty good job of presenting the actual argument for microbiome
experimentation at the end:

>our genomes have had little time to adapt to modern life, but our microbiomes
have had plenty.

>It may be that a Hadza microbiome would work equally well in an American gut,
but incompatibilities are also possible. The conquistadors proved as much. As
they colonized South America, they brought with them European strains of
Helicobacter pylori, a stomach bacterium that infrequently causes ulcers and
stomach cancer, and these European strains also displaced native American
ones. This legacy persists in Colombia, where some communities face a 25-fold
higher risk of stomach cancer, most likely due to mismatches between their
ancestral genomes and their H. pylori strains.

------
johnvschmitt
If you brush before sleep (with triclosan, a very common antibacterial agent),
you breathe >25% of your breaths through a mouth populated with antibacterial
agents.

The prevalence of antibacterial agents in soaps, & toothpastes in the last 15
years coincides with the increases in asthma & digestive disorders.

The article says, essentially, "It's complex, and adaptive, so be careful how
you force it away from a neutral state." Yet, adding antibacterial agents to
toothpastes is quite a forceful change.

------
tomcam
Bonus points for the quote _This befuddling complexity is not confined to the
vagina._

------
dlss
This article doesn't seem to consider the alternative hypothesis very
seriously, so as one of the biohackers Ed is no doubt referring to, I'll do my
best to summarize why it's not unreasonable to act before all the data is in.

Our knowledge about the microbiome is similar to our knowledge of nutrition:
we don't know enough to claim optimality, but we do know enough to say that
the modern default is bad.

My product is the microbiome equivalent of the paleo diet -- it simply
restores non-pathogenic microbes which were the unintended victims of
widespread food sterilization. In our (admittedly small) pilot study, over 90%
of people felt this helped their digestion.

I believe this approach is _more_ cautious than continuing to eat a modern
diet. We didn't evolve eating sterile food.

[http://www.generalbiotics.com/probiotics](http://www.generalbiotics.com/probiotics)

~~~
001sky
"we do know enough to say that the modern default is bad."

Could you articulate why this statement is even plausible?

~~~
dlss
Interesting. To be clear, the current state of affairs is eating sterilized
food (often required by law to control pathogens), and taking antibiotics
every 2 years[1].

This is bad a priori, since it's two deviations from the only known good
condition -- the one we evolved in.

But I take it that argument was non-persuasive.

So here are some other people discussing the idea: The hygiene hypothesis[2]
is broadly the theory that diseases of affluence[3] are related to living in
overly sterilized conditions. Most if not all of the items discussed in [3]
are correlated with your microbiome[4], with large studies underway to
determine the role in more detail [5].

Okay, hope this helps. To answer your question a third way: most biologists
working on the microbiome think it's plausible.

[1]
[http://www.nejm.org/doi/full/10.1056/NEJMc1212055](http://www.nejm.org/doi/full/10.1056/NEJMc1212055)

[2]
[http://en.wikipedia.org/wiki/Hygiene_hypothesis](http://en.wikipedia.org/wiki/Hygiene_hypothesis)

[3]
[http://en.wikipedia.org/wiki/Diseases_of_affluence](http://en.wikipedia.org/wiki/Diseases_of_affluence)

[4]
[http://academy.asm.org/images/stories/documents/FAQ_Human_Mi...](http://academy.asm.org/images/stories/documents/FAQ_Human_Microbiome.pdf)
\-- see pages 11+

[5] We have a bibliography at
[http://www.generalbiotics.com/science](http://www.generalbiotics.com/science)

edit: my co-founder wishes me to point out that I wrote this was to illustrate
why eating ancestrally normal microbes is a plausible idea. Please don't take
these links as me saying my product can prevent any diseases -- I don't have
sufficient evidence to support that claim.

