Friday, July 22, 2016

Today's misleading overselling the #microbiome - U. Chicago on Alzheimer's and gut microbes

Well, this is disappointing if not disturbing

A new paper is out that has some interesting findings but the paper itself, and the press release form the authors (at University of Chicago) really goes overboard in misstating the findings.

Here is the paper in Scientific Reports. I purposefully am not putting the title of the paper here in the post yet, because amazingly, even the title is misleading.

But here is what a summary of what they showed, based on their results section, which seems interesting and sound
  • Antibiotic treatment of a variety of mice showed alterations in the GI microbiome and in various inflammatory markers circulating in the blood
  • Male mice treated with this antibiotic regime showed reduced Aβ plaque deposition but increased soluble Aβ levels
  • Reactive gliosis surrounding Aβ plaques is reduced in male mice treated with this antibiotic regime 
This is not all they report as they also discuss various controls and other observations about these mice and their brains and their responses to the antibiotic treatment.  

But what they do not report on is any evidence of anything other than a correlation between the GI microbiome changes and the inflammatory markers and the reduced Aβ plaque deposition.  They even state this VERY BRIEFLY in their paper
We are fully cognizant of the fact that the findings reported herein are purely correlative and do not elucidate precise mechanism(s). 
Yet then through other papers parts of the paper they misstate what they find and somehow, almost magically, turn this correlation into evidence for a causative connection.  For example in the abstract
These findings suggest the gut microbiota community diversity can regulate host innate immunity mechanisms that impact Aβ amyloidosis.
No. These findings are consistent with that.  They are also consistent with, for example, the antibiotics affecting microbes in the brain which in turn could affect inflammatory markers.  Or microbes on the skin.  Or in the blood.  Or elsewhere.  I don't see any evidence here for a causative connection between the gut microbes (which are certainly affected by these antibiotics) and the plaque.

Yet even worse is that this misrepresentation of a causative connection makes it into the title of the article
Antibiotic-induced perturbations in gut microbial diversity influences neuro-inflammation and amyloidosis in a murine model of Alzheimer’s disease

No no no no no no no no.  No evidence that the perturbations in the gut microbes are directly influencing anything in the brain.  It is a good model.  But they need to be more careful with their wording.

And sadly, this gets even worse in the press release about the paper: Antibiotics weaken Alzheimer's disease progression through changes in the gut microbiome | EurekAlert! Science News

What?  This "through changes in the gut microbiome" is just completely misrepresenting what was shown in the paper.

Here are some misleading parts of the PR
The study, published July 21, 2016, in Scientific Reports, also showed significant changes in the gut microbiome after antibiotic treatment, suggesting the composition and diversity of bacteria in the gut play an important role in regulating immune system activity that impacts progression of Alzheimer's disease.
Nope. Nope. and Nope.

Thankfully there are a few caveats in the PR too but that does not balance misleading statements.  The worst is saved for the end
"There's probably not going to be a cure for Alzheimer's disease for several generations, because we know there are changes occurring in the brain and central nervous system 15 to 20 years before clinical onset," he said. "We have to find ways to intervene when a patient starts showing clinical signs, and if we learn how changes in gut bacteria affect onset or progression, or how the molecules they produce interact with the nervous system, we could use that to create a new kind of personalized medicine."
Basically, saying there will be a cure for Alzheimer's. And then saying if we learn HOW (not if) gut microbes affect onset or progression, then we can better cure or treat this disease.  This is just too bold and misleading for my taste.  Nice paper.  Interesting work and implications. But it is misleading to say they have shown any causative connection between gut microbes and Alzheimer's in this paper and also very misleading to start to talk about how they will use this to lead to treatments or cures.

Oh, and did I mention this was in mice not humans?  So how do they get from a correlative study in mice to how gut microbes affect progression of Alzheimer's in humans?  Really this is not OK, even to hint at.

And of course, which such misleading material in their own paper and in their PR it is not surprising that some of the reporting on this is going awry.

See the Daily Express for example

And the Business Standard

And I am sure many more to come.  Scientists have to be more careful with discussing and presenting the implications of their work.  I love the microbiome field and the possible implications to me are enormous for the role of the microbiome in various areas of biology.  But misrepresenting ones findings, especially when it comes to human diseases, is dangerous and bad for science and bad for the microbiome field.  The author's of the paper and the people behind the PR at the University of Chicago should publish a correction of the PR and also publish a correction of their paper to correct the misleading representations. And for their misleading material in their paper and in the PR I am giving them a coveted "Overselling the Microbiome" award.

Some responses

Minor correction made


And scarily, one of the authors of the paper, Rudy Tanzi is using the paper to promote his book and his claim that Alzheimer's can be prevented through manipulation of the microbiome

UPDATE 2 -- July 24 - 8:50 AM

I have written to the author of the PRs at U. Chicago to ask for a correction to be made

UPDATE 3 -- July 24, 9 AM

So many people posting links to the misleading articles where all that comes through (e.g., on Twitter) is the headline including the misleading information about the gut. Am responding to many of them but not all.

Fortunately, Argonne National Lab responded quickly

UPDATE 4 --- July 24 11:30 AM

I also will contact the author of this article on ScienceNews: Antibiotics might fight Alzheimer’s plaques  because it also has some misleading statements about the gut microbiome connection

Image caption:
PLAQUE FIGHTER  A long dose of antibiotics reduced Alzheimer’s-related plaques (shown here in a human brain) in the brains of mice, results that suggest gut bacteria can influence the disease
1st sentence does better
A long course of antibiotics reduced the levels of a hallmark of Alzheimer’s disease in the brains of mice, possibly by changing the species of bacteria in the gut
But then it reverts
This microbial shift in the gut appeared to affect the brain.
And continues with more
Sisodia and colleagues don’t know how bacteria signal from the gut to the brain to affect A-beta, although their study raises one possibility. 
And then this
If a similar relationship between gut bacteria and Alzheimer’s does exist in people,
UPDATE 5 --- July 24 11:45 AM

Sent an email to the author.

1 comment:

  1. From Claudiu Bandea who was having trouble posting his comment so asked me to do it.

    Whether the statements and conclusions drawn by Minter et al. are supported directly by their data or not becomes a minor issue if eventually proven to be correct, which is likely to be the case. I think that’s what the authors are banking on.

    Indeed, there is relevant data and observations on the etiology of Alzheimer’s, Parkinson’s, Huntington’s, ALS and other neurodegenerative diseases that link the microbes/viruses and innate immunity to the pathogenic mechanisms leading to these devastating diseases. And, at least one of the authors of this article, Dr. Rudolf Tazi, had jumped on this bandwagon, albeit sporadically (see my PubMed Commons on a recent paper, “Amyloid-β peptide protects against microbial infection in mouse and worm models of Alzheimer's disease,” he co-authored (

    Perhaps the following study entitled “Reduction of Alzheimer's disease beta-amyloid pathology in the absence of gut microbiota” by Harach et al. (, which is not mentioned in their paper, had given Minter et al. the confidence to advance their ‘visionary’ statements. And, clearly, these statements are within the framework a radical new theory on the etiology of Alzheimer’s, Parkinson’s, Huntington’s, ALS and other neurodegenerative diseases ( This theory questions the validity of the ‘protein misfolding’ and ‘prion’ paradigms, which have directed most of the research in these field in the last few decades. It is not surprising, therefore, that this theory has yet to resonate with most researchers in the field who have promoted these paradigms. Nevertheless, with Dr. Tanzi’s ‘help’ and promotional work (J), it will certainly make some inroads soon.