And in non shocking news of the day – more overselling of the microbiome

Well, just read this story: Possible link between bacteria and breast cancer: study | CTV London News.  Serious overselling of the microbiome going on here.  As far as I can tell, all that was shown in the work discussed here (for which there is no publication or presentation of any kind reported) is that the bacteria found in canecrous breast tissue differs from that in non cancerous tissue.  Interesting perhaps.  But not really that informative as just about every time anyone has ever looked at two samples from patients with different health conditions, the microbiome is different.  Much worse that suggestions about the meaning of the differences they observe, the article then goes on to state:

And since we know that priobiotics can positively affect gut health, might the same beneficial substances influence breast health? Related bacterial research offers tantalizing possibilities. 

“It shows you how closely associated microbes are with our body and our health,” Reid says. “And therefore when you try and modulate them through probiotics chances are you could have an effect that’s beneficial.”

What?  Not only does Dr. Reid say, incorrectly, that “chances are you could have an effect that’s beneficial” simply by trying to use probtiotics to modeulate health.  But the whole ending to the article implies that somehow, magically, probiotics are a good idea for preventing breast cancer.  Uggh.

Winner of the biggest & best overselling of the microbiome -@theallium on Salmonella Diet

OK.  Now this is some serious overselling of the microbiome: New Salmonella diet achieves “amazing” weight-loss for microbiologist | The Allium.  A must read for anyone interested in microbes and microbiomes.  My favorite part:

“For some time now, we have known that the microbes of the gut – what we term the “microbiome” – play a very important role in our daily lives. What we eat, how healthy we feel, etc. is all controlled by our microbiome. In fact, nothing else is important to our health, except the microbiome – it can defeat cancer, cure hunger, poverty, restore amputated limbs, everything”, said Dr. Nofit.

Although it might seem to be an exaggeration, I think this Dr. Nofit must be correct.  I will now never claim that anyone has oversold the microbiome, because, well, it does everything.

Overselling the microbiome story of the week: aging in fruit flies vs humans

Well, I like fruit flies too.  But the claims in this story are quite a jump: Gut bacteria health may be the key to living longer, disease-free lives, U.S. fruit fly study reveals | National Post.

Some choice quotes:

Researchers have more than just a gut feeling they’ve discovered one of the keys to living a longer, healthier life, especially as we age.

Emphasis on we by me.  Jumps right in there and basically says this study is about people even though it is not.

But this research goes further, study authors said, putting gut bacteria shifts “into a hierarchical, causal relationship and highlights the points where we can intervene.”

Where we can intervene in all the premature aging that happens in the fruit flies in our houses.

“If we can understand how aging affects our commensal population (the bacteria that live inside us) — first in the fly and then in humans — our data suggest we should be able to impact health span and life span quite strongly,” Jasper said. “Because it is the management of the commensal population that is critical to the health of the organism.”

How does Jasper go from their fruit fly study to “we should be able to impact health span and life span quite strongly.”???????  Again, I love fruit flies.  And I love their microbiome.  I think that Drosophila is a great model system for studying animal microbiomes.  I have even coauthored a few papers on Drosophila and the microbes that live in and on it.  Examples include

But let’s not get ahead of ourselves in the implications of this work for humans.

Short post- a bad taste in my mouth for overselling the microbiome

Well, this just leaves a bad taste in my mouth: Oral Bacteria Create a ‘Fingerprint’ in Your Mouth.  Basically, the researchers compared microbial diversity in the oral microbiome of people and they looked at how correlated the microbiome was with ethnicity.  And they published a PLOS One paper and wrote a press release about it.  And there are many lines in the PR and some in the paper I take issue with.  These include:

  • PR: “The most important point of this paper is discovering that ethnicity-specific oral microbial communities may predispose individuals to future disease”.
    • Uggh.  I cannot find anything anywhere that indicates anything about predisposition to disease
  • PR: “Nature appears to win over nurture in shaping these communities,” Kumar noted, because African Americans and whites had distinct microbial signatures despite sharing environmental exposures to nutrition and lifestyle over several generations.
    • Double uggh.  So – different ethnic groups have different microbes.  And since some of the ethnic groups have similar environmental exposures to each other (actually, they do not even test this – they simply assume this) yet do not have similar micro biomes, therefore the cause of the differences in the microbiomes must be genetic differences between the ethnic groups.
  • Paper: “Our data demonstrates that ethnicity exerts a selection pressure on the oral microbiome, and that this selection pressure is genetic rather than environmental, since the two ethnicities that shared a common food, nutritional and lifestyle heritage (Caucasians and African Americans) demonstrated significant microbial divergence.” 
    • Triple uggh.  This should not have been allowed in the paper.  Their work in no way demonstrates any genetic component to the differences in the microbiome.  

This is certainly a case of overselling the microbiome.  But it is also a case of just bad science in relation to the “nature vs. nurture” issues.

Lies, damn lies, and press releases – trouble with recent PR about autism and microbiomes

Uggh.  Just saw a bunch of stories about autism and the microbiome.   Many of the comments in the news stories I read seemed, well, not so good.  So I decided to sniff around.  Seems that many of the comments and stories are based on a new PLOS One paper and the comments and press release from the group behind the paper.

Here is the press release I found: Clues about autism may come from the gut.  From Arizona State University.   So I read it.  But I had a hard time getting past paragraph 2:

In new research appearing in the journal PLOS ONE, a team led by Rosa Krajmalnik-Brown, a researcher at Arizona State University’s Biodesign Institute, present the first comprehensive bacterial analysis focusing on commensal or beneficial bacteria in children with autism spectrum disorder (ASD).

This did not sound true and sounded a bit overblown as I could have sworn I had seen other “comprehensive” studies of the microbiome in children with ASD. So first I decided to look at the paper.  And – thanks a lot – there was no link in the PR or the stories I had seen.  So I had to go to PLOS One and do a little searching and I found it:

Reduced Incidence of Prevotella and Other Fermenters in Intestinal Microflora of Autistic Children

Kang D-W, Park JG, Ilhan ZE, Wallstrom G, LaBaer J, et al. (2013) Reduced Incidence of Prevotella and Other Fermenters in Intestinal Microflora of Autistic Children. PLoS ONE 8(7): e68322. doi:10.1371/journal.pone.0068322

So – first I asked – did they make the same claim in the paper or was this just in the PR?  Usually such things are just in the PR but amazingly they have this claim in the paper too, with lines like:

“previous studies describing the relationship between autism and gut microbes have either mostly focused on the emergence of harmful bacteria or mainly paid attention to already-known beneficial bacteria”

So I decided to then look at Pubmed and Google Scholar for other papers on autism and the microbiome. Here are some that I found:

Not all of these are what one would call comprehensive.  But some of them are at least approaching the scale of what was done here.  And surprisingly, not all of them are cited in the new study.  In particular, the papers by Gondalia et al including one on “Molecular Characterisation of Gastrointestinal Microbiota of Children With Autism (With and Without Gastrointestinal Dysfunction) and Their Neurotypical Siblings” is not references despite it doing some similar things.  I guess, if you don’t cite other comparable studies, and pretend they don’t exist, then that makes one’s work seem a but more novel right?  Weird not to cite that work though – not sure why that happened.  And certainly some of the other studies, even though they are cited, seem like they could be referred to as comprehensive.  I mean – Ian Lipkin’s study did metagenomics not just PCR based sequencing.  Isn’t metagenomics sort of more comprehensive than PCR?  
Anyway – let’s just say this is not the first “comprehensive” study of autism and the microbome.
Moving on in the press release I encountered another painful statement.

The work also offers hope for new prevention and treatment methods for ASD itself, which has been on a mysterious and rapid ascent around the world.

Just what exactly does this new study say about prevention or treatment?  Actually, as far as I can tell – nothing.  So this is a bonus overselling statement just for the PR
Oh but then the PR just get’s worse:

Their new study is the first to approach autism from a different angle, by examining the possible role of so-called commensal or beneficial bacteria.

Seriously?  We have gone from trying to claim this is the first comprehensive study of the microbiome and autism to now saying it is the first?  Fu#*(@@# ridiculous.
Other lines that are troubling are encountered further on including
  • The authors stress that bacterial richness and diversity are essential for maintaining a robust and adaptable bacterial community capable of fighting off environmental challenges.”.  Hmm.  What is the difference between richness and diversity? And what is the evidence that they are essential for such functions?
  • The species is a common component in normal children exhibiting more diverse and robust microbial communities.”  Again – what makes that robust?
  • Michael Polan’s recent New York Times Magazine story on the microbiome points to the fact that he is proud that his gut microbiome is rich in Prevotella regarding it as a possible sign of a healthy non-Western diet.  Really?  They brought Michael Pollan (with a mis-spelling that might be on purpose so that Pollan does not see this) into their PR?  Uggh
Anyway – I kind of wanted to give them an overselling the microbiome award for some of their statements.  But in the end I would rather give them an “Overselling ourselves” award.  It is a shame too.  I think continuing to explore possible connections between autism and the microbiome will be important.  Making misleading statements about what you have done and not citing / properly referencing other work will not help.

Yes, microbes are likely important everywhere, but evidence would be nice (re Atlantic piece on Soil)

Just read this article in the Atlantic: Healthy Soil Bacteria, Healthy People – Mike Amaranthus & Bruce Allyn – The Atlantic.  It is interesting in a few ways.  But what got me a bit up in arms about it is the number of statements and claims that are not backed up by any reference to evidence.  Consider the following:

“Just as we have unwittingly destroyed vital microbes in the human gut through overuse of antibiotics and highly processed foods, we have recklessly devastated soil microbiota essential to plant health through overuse of certain chemical fertilizers, fungicides, herbicides, pesticides, failure to add sufficient organic matter (upon which they feed), and heavy tillage.”

OK – sounds serious.  But is it really true?  Have pesticides really devastated soil microbiota?  What about tillage?  Seems possible, but also seems possible that this would not be true.  Would be nice to see the evidence behind this claim.

How about this one:

“Reintroducing the right bacteria and fungi to facilitate the dark fermentation process in depleted and sterile soils is analogous to eating yogurt (or taking those targeted probiotic “drugs of the future”) to restore the right microbiota deep in your digestive tract.”

Sounds good too.  But way too overly simplistic.  I mean – probiotics for people are a bit of a complicated mess right now.  Some work.  Most probably don’t.  Most of the claims are overblown.  So to say we know how to do this well in “soil” definitely seems to be an overstatement.  Again, specific evidence for this would be nice.

And then this:

“Due to new genetic sequencing and production technologies, we have now come to a point where we can effectively and at low cost identify and grow key bacteria and the right species of fungi and apply them in large-scale agriculture.”

Soil is a very very complicated place in terms of microbes.  I personally think we are really far away from this utopian view of growing the key species to apply them to large scale ag.  Evidence that this is true?  I don’t know of much.  Yes we can sequence things.  We can sequence a lot of things.  But “identify and grow key bacteria and the right species of fungi” – I think we are far from being able to do this robustly.

Another claim in the article has some ring of truth:

We can sow the “seeds” of microorganisms with our crop seeds and, as hundreds of independent studies confirm, increase our crop yields and reduce the need for irrigation and chemical fertilizers.

Yes, this has a ring of truth.  Certainly there are studies – many of them – involving adding microbes to seeds and how that impacts yield and nutrient and water requirements.  And without a doubt in many cases such inoculation can help in many ways.  But the “hundreds of independent studies” claim is a bit misleading as there are also many cases where inoculation does not help.  So we should be cautious before adding microbes to seeds becomes the equivalent of probiotics for people.   Not all probiotics that are claimed to help people actually do anything.  And not all microbes added to seeds will do much of anything useful either.

How about the claim:

Thus the microbial community in the soil, like in the human biome, provides “invasion resistance” services to its symbiotic partner. We disturb this association at our peril

Sounds good.  And has a ring of truth too.  And in general I agree with the sentiment that we should not screw with ecosystems without recognizing that the microbes in those systems may play important and useful roles.  However, just because SOME microbes play important and useful roles in systems does not of course mean that ALL are ones we want to keep.  There will be some in the soil that damage plants and hurt yield and pathogen resistance just as there will be some that are “good” from our point of view.

And then there is this

We are now at a point where microbes that thrive in healthy soil have been largely rendered inactive or eliminated in most commercial agricultural lands; they are unable to do what they have done for hundreds of millions of years, to access, conserve, and cycle nutrients and water for plants and regulate the climate. 

And also

The mass destruction of soil microorganisms began with technological advances in the early twentieth century. 

Sounds nice.  But I don’t really know of much evidence that the microbes have been rendered inactive or eliminated in commercial agricultural lands.

I suppose this is all building up to the following

Fortunately, there is now a strong business case for the reintroduction of soil microorganisms in both small farms and large-scale agribusiness. Scientific advances have now allowed us to take soil organisms from an eco-farming niche to mainstream agribusiness. We can replenish the soil and save billions of dollars.

and

For all these reasons, bio fertility products are now a $500 million industry and growing fast. The major agricultural chemical companies, like Bayer, BASF, Novozymes, Pioneer, and Syngenta are now actively selling, acquiring or developing these products.

So — this is in a way an article promoting the financial benefit of adding microbes to soil.  I think this is reasonable although not completely convincing.  Alas, after reading the article I discovered this about one of the authors

Mike Amaranthus is the chief scientist at Mycorrhizal Applications, Inc., a company working on innovations in soil biology. 

This is not to say that someone with a financial role in convincing the world to add microbes to soil cannot be trusted to provide a good guide about microbes in the soil.  But it would have been nice for this to be mentioned more prominently in the article.  Many of the claims in this article do not pass the smell test to me.  And all of them seem to be pointing towards a solution involving a company that one of the authors is involved in.  If this were about human medical treatments many many people might get bent out of shape by this.  Again, not to say people with financial interests cannot write good articles.  But the potential for conflicts in such cases, as in the case here, is great.  And thus we should view with a tint of extra skepticism some of the claims made by such individuals.  And in this case here I already felt uncomfortable with many of the claims.  I think the Atlantic could do better and could certainly require the author to make more clear in the article itself  what the author’s personal interest in the claims are.

First multiple "Overselling the microbiome award": the Daily Mail article on Germs

At the recent “Future of Genomic Medicine” meeting, George Church gave me some grief over my “Overselling the microbiome award” because he thinks (rightly) that some people also undersell the microbiome.

So I set out today to find an example to give out such an award.  And within seconds I bumped into this: Germs: There are bugs that cure infections, protect against stroke and even keep your skin clear | Mail Online in the Daily Mail.

 Wow.  And not in a good way.  Oh well, so much for the underselling award.  Just the title made me cringe.  And so so so so many of the details are so so bad.

Where to start.  I guess from the beginning.

“.The secret lies in the balance of the bugs, which exist in a fragile ecosystem. Knock one out and the system goes haywire.”

Umm.  No.  Not that I know of.  Knock one out?  What evidence is there for this?  None.

“Imbalances in gut bacteria, for instance, have been linked with diabetes, obesity, autism, eczema, psoriasis, asthma and inflammatory bowel conditions such ulcerative colitis and Crohn’s disease”

“…. may even … cause … multiple sclerosis “

Holy crap.  That sounds awesome.  Except that there are all correlations so far with no known causative role at least in humans.

Then they list some of the other good things microbes apparently have been proven to do:

“ANXIETY-BUSTING GUT BACTERIA”
“It seems that the type of bugs you have in your body can affect mood.”

Though at least in this section they do refer to a mouse study but clearly imply this is true in humans too.  It may be.  But I am unaware of any studies proving it.

“BUGS ARE GOOD FOR YOUR SKIN”
“It’s a common misconception that the cleaner the skin, the better — and the bacteria that live on our skin have an important role.”

I am all for not killing all microbes willy nilly but their is certainly one part of the body that you probably do want to wash a lot – your hands.  So As long as they don’t say “Don’t wash your hands” this could be OK.

So what do they say next:

‘If you wash your hands repeatedly, they dry out — this is partly because you wash away all the oils but also because you remove a large number of the bacteria that help maintain the skin’s condition,’ says Professor Mark Fielder, a medical microbiologist at Kingston University.

Oh FFS now they are basically telling people to not wash their hands.

“SHARE A KISS… AND BACTERIA”
‘Every time you kiss, for example, you exchange a million bacteria. ‘So your gut microbiology becomes close to that of your loved ones.’

Sounds great.  I could not find any references on the topic but sounds great.

“SOME TYPES MAY PREVENT STROKE”
Wherein the tell a story based on a press release which had led me to post the following: “Award: Ridiculous, absurd, offensive overselling of the microbiome from Chalmers & Gothenburg”.  Any idea if I think this is an accurate press release?

TRANSFUSION TO BEAT INFECTIONS
Wherein they discuss fecal transplants for C. difficile infections, which seem to work quite well and I have written about a lot (e.g. Transfaunation and Fecal Transplants: What Goes Around Comes Around, Literally and Figuratively).  But then they kill their positive mojo on the topic by writing:

Lawrence Brandt, a professor of medicine and surgery at New York’s Albert Einstein College of Medicine, believes the treatment could work for other, non-gastro conditions, such as obesity and Parkinson’s.

Seriously?  Fecal transplants for Parkinson’s?

And it goes on and on including:
“SOME BACTERIA KEEP YOU SLIM”
BUGS THAT HELP MEDICINE WORK”
“COULD THEY WARD OFF CANCER?”
“KEY TO BABIES’ IMMUNITY”

I mean – I really really do think the microbiome plays roles in many many parts of our lives.  But those who promote it this much are the snake oil sellers of the modern era.  A slight of hand here and soon they will be selling us some specific brand of probiotic or way to protect our microbiomes.  So for this article the Daily Mail is getting my first multiple “Overselling the microbiome award.”  They could get 3 or 4 just from this article if not more.  But I will just give them two.  And I will keep searching for an underselling the microbiome recipient.

Dr. Mercola offers up some serious BS on probiotics and the human #microbiome

Aaarrrg.  Well, I was snooping around google news, search for “archaea” and this came up: foodconsumer.org – How Your Gut Flora Influences Your Health.

The archaea reference was in a quote that this article made of a Science Daily report

The microbes in the human gut belong to three broad domains, defined by their molecular phylogeny: Eukarya, Bacteria, and Achaea.

Wow – this surprised me.  An article at some place called Food Consumer that was mentioning archaea.

But that was pretty much the only decent part.  Things went downhill fast with a link to some total BS on a way to cure every disorder on the planet by focusing on gut microbial health.

The article then pulls a classic trick – referencing some of the new human micro biome work in Nature to make the discussion here seem scientific. But alas it is not.  Consider this doozy of a line

The ideal balance of beneficial to pathogenic bacteria in your gut is about 85 percent good bacteria and 15 percent bad.  Maintaining this ideal ratio is what it’s all about when we’re talking about optimizing your gut health. “

Yes that is right everyone – you want to maintain a ratio where 15% of the bacteria in your gut are pathogenic.  Aaarrggh.

Not surprisingly, when I searched around the web for detail on the person behind this article – some Dr. Mercola – who I have never heard of – I discovered that he is considered by many to be a quack.  No disagreement from me.

Diabetes & H.pylori – a correlation but no known causation despite authors claims

Am having a hard time right now with the comments from the authors of this new paper showing a correlation between H. pylori presence and both type II diabetes and blood glucose levels.  As far as I can tell, the paper does not show any causal connection.  That is, they do not determine if H. pylori infection is a cause of blood sugar issues or a consequence of blood sugar issues.

Yet the authors of the paper, one of whom (Martin Blaser) is a very respected H. pylori expert are saying things like

This study provides further evidence of late-in-life cost to having H. pylori,

And they suggest that antibiotic treatment for the elderly may help prevent diabetes.

This to be seems to be a bit over the top.  Yes, it makes sense that H. pylori could cause these issues.  And they have a model for how it might.  But they really should be more careful with their words until a causal connection is established.  After all, we have many well known negative effects of antibiotic overuse, including some shown by Blaser.  The last thing we need is people going out and dosing up on antibiotics in the hope that it will prevent type II diabetes.  But I can guarantee that is what will happen if this story gets overplayed.

At least a few sources report on the lack of anything showing a causal connection (e.g. see US News and World Report):

An expert not involved with the study said that while it did not show a cause-and-effect relationship between the bacterium and diabetes, the findings suggest certain possibilities

But I am worried that that is not enough skepticism to counteract the claims of the authors here. The study is certainly interesting.  And their model for a causal connection is fine.  But they probably need to do a little bit of toning down of their claims here.

UPDATE: 3/17/13

After some people asked me questions about this study at a few recent meetings I dug a little deeper.  And I am a bit startled to find out what the basis is for Chen and Blaser to claim a causative association between H. pylori and type II diabetes/ glucose levels.  Here is a summary of their logic:

Helicobacter pylori is acquired almost exclusively in childhood [8], and there is no clear mechanism for how glucose intolerance present only after the age of 18 would increase risk of H. pylori colonization. It also is unlikely that H. pylori positivity and high levels of HbA1c levels share a mutual antecedent cause because there is no diathesis to both acquire H. pylori and to cause glucose intolerance.

They go on to discuss other lines of indirect evidence for why they think their conclusion is correct.  And some of this is very suggestive.  But “likely” and “suggestive” is not proof.  There are many possible issues with their conclusion.  In particular I think it is easy to come up with a scenario whereby something about the host (either their genetics or their history of exposure or even their micro biome) could influence both whether or not they get colonized by H. pylori or even whether or not they get colonized by particular strains of HP.  And the same factor could influence microbiome interactions later in life.  I see no evidence to indicate that H. pylori is the causative agent here.  And for them to then basically recommend prophylactic antibiotics for elderly with HP seems dangerous at best.