Treponema are not "ancient" but absence from some human’s guts is very interesting

So I saw some Tweets today that caught my attention, discussion news stories about “ancient” bacteria being missing from some human’s gut microbiomes:



These refer to a sadly inappropriate headline in Science

What is wrong with this?  Well, there are no “ancient” bacteria around today.  They are all modern.  I am not even sure what they were trying to say.  Just a really bad evolution argument I guess.  I pondered giving Science a Twisted Tree of Life Award which I give out for exactly this kind of thing –  but decided first to dig into the science here and gloss over the bad evolution headline.

And it turns out – what the news story is about is in fact interesting – a new paper out in Nature Communications:  Subsistence strategies in traditional societies distinguish gut microbiomes.

The paper is freely available and has some really interesting material in it.  They key to me – at least related to this “ancient” bacteria claim is the following part of their abstract:

As observed in previous studies, we find that Treponema are characteristic of traditional gut microbiomes. Moreover, through genome reconstruction (2.2–2.5 MB, coverage depth × 26–513) and functional potential characterization, we discover these Treponema are diverse, fall outside of pathogenic clades and are similar to Treponema succinifaciens, a known carbohydrate metabolizer in swine. Gut Treponema are found in non-human primates and all traditional peoples studied to date, suggesting they are symbionts lost in urban-industrialized societies.

And then some further detail in the paper:

Although Spirochaetes have been previously reported from the gut microbiome of non-human primates and ancient human populations, they have only been observed in high abundance among extant human populations with non-Western lifestyles, such as a traditional community in Burkina Faso and a hunter-gatherer community in Tanzania. As such, they may represent a part of the human ancestral gut microbiome that has been lost through the adoption of industrial agriculture and/or other lifestyle changes. 

So they don’t go into the full detail here but what I think they are saying is that they infer that human ancestors had Spirochaetes (based on the finding of it in non human primates and some human populations).  And thus they further infer that human populations (e.g., the people they studied in Oklahoma) that do not have these Spirochaetes have “lost” them.

I note – I think this terminology of “loss” they are using is not quite right here in a way.  Saying that these Spirochaetes have been lost implies to me that they are heritable.  But they do not in fact show that.  It could be that these are related to diet or environment in some way – something shared by some human populations and non human primates, for example.  And thus the absence from some “Westernized” populations could be more of an environmental thing than a “loss” in the past.

In a similar way, we could say that Westernized humans have “lost” the ability to be skinny (since obesity is high in many such populations).  Non human primates have such abilities and so do some non Westernized populations.  But “losing skinnyness” does not seem quite right since we do not know exactly why obesity is higher in Westernized populations.  I think it would be better in such cases to say something like “do not show an ancestral trait” (the ancestral trait here being skinnyness) and to not use “lost” until we know more about what is going on.  Similarly, I think saying some human populations have “lost” these Spirochaetes is not quite right.

Nevertheless, the absence (or at least, low levels) of these Spirochaetes from some human populations is certainly interesting.  And given that the presence of such Spirochaetes does appear to be an ancestral trait, the absence is even more interesting.  And thus this paper here, which details some of the genomic features of these “missing” Spirochaetes is definitely worth paying attention to.

In addition, I note – the findings in this paper serve as an additional justification for projects to generate genomic data from across the phylogenetic diversity of microbes.  Consider for example their Figure 6 and 7 which show that the most closely related Treponema species and the ones with the most similar genomes to these human Spirochaetes are those from Treponema succinifaciens and Treponema brennabornese.

Both of those genomes were generated by the Genomic Encyclopedia of Bacteria and Archaea project which I coordinated with the DOE-JGI and DSMZ.  See the paper on one of them: Complete genome sequence of Treponema succinifaciens type strain (6091T) and the posted data on the other.

We argued that we needed to sequence reference genomes from across the tree of life because this would help inform studies of uncultured microbes from diverse ecosystems.  Little did I know that one of the key ecosystems we would help inform would be the human gut.

Certainly more needs to be done in regard to these Spirochaetes.  Why are they at low levels or missing from some Westernized populations?  What do they do in other populations?  Would they be helpful if they were reintroduced to populations that do not have them?  So many questions actually.  But despite the misleading news article headline, this paper seems to me on first glace at least to in fact be quite interesting.

I made a Sorify of some comments

Please make it stop – overselling the microbiome award for rugby, exercise, microbiome stories

Update added 11/2/14 – for all my posts on Overselling the Microbiome go here. 

Well, I think today’s lesson is, many people, including many scientists and science reporters, just do not get that there is a difference between correlation and causation.  I know – this is like beating a dead horse since many write about this issue.  But it just needs to be called out every time until it stops.  And today’s fun comes from stories and the original research articles about how exercise supposedly alters the gut microbiome.

I was pointed to this just a few minutes ago on Twitter:

In this Tweet Bernat Olle points to a “news” story in Medpage Today: Exercise Boosts Gut Microbiome Diversity by Kristina Fiore.   Well, so of course I started digging around.  And, not surprisingly, the study that this is based on shows absolutely no causal connection between exercise and the gut microbiome.  The study is in the journal “Gut”: Exercise and associated dietary extremes impact on gut microbial diversity.  And here is what they did:

  • They selected subjects – 40 “elite” rugby players.
  • They identified healthy male “controls” with similar age and size and from similar place. 
  • Then they collected faecal and blood samples from participants and did surveys about their nutrition and clinical data.
  • Among many measurements, they did 16S sequencing from the fecal samples
  • Then they did some bioinformatics and found differences between the rugby players and the controls in many features including microbiomes.
And amazingly, from this they report, in their abstract

The results provide evidence for a beneficial impact of exercise on gut microbiota diversity but also indicate that the relationship is complex and is related to accompanying dietary extremes.

The key part of this to me is 

The results provide evidence for a beneficial impact of exercise on gut microbiota diversity

For which they have no support.  They do not in any way show that exercise has ANY affect on the microbiota.  They show it is correlated to the microbiota.

And sadly there is a commentary on the article in the same issue of Gut that makes the same mistake.  Georgina Hold in The gut microbiota, dietary extremes and exercise writes:

The article is the first report that exercise increases gut microbiota richness/diversity and highlights that exercise is another important factor in the complex relationship among the host, host immunity and the microbiota.

No.  They did not show exercise increased gut microbiota diversity.  How can the difference between correlation and causation be missed in these articles?  Are these not even reviewed?  Sure – this is consistent with exercise affecting microbiomes but it is also consistent with rugby players having different diets and other behaviors.  There is a big difference between showing cause and effect and showing correlation.  For not distinguishing between correlation and causation regarding the rugby player microbiomes I am giving all involved here an “Overselling the Microbiome Award“.

Here is a microbiome theory I will leave you with.  I hypothesize that these papers, and all the other ones that oversell the microbiome, themselves cause major changes in the microbiome of many people.  Evidence for this?  Well, none yet.  But I have a correlation.  The correlation is, after reading these papers,  I feel sick to my stomach.  That must be proof right?

UPDATE 6/11/14

Author of the Medscape Medpage today article Kristina Fiore says she will update the article to more accurately reflect the science. See some of the thread below




UPDATE 2: 6/11/14.

The press release from Gut associated with this paper contains many inaccurate statements.

Examples include:

  • Title: Exercise boosts diversity of gut bacteria
  • Text: Exercise boosts the diversity of the bacteria found in the gut, indicates the first study of its kind published online in the journal Gut.
Somewhat surprised that such mistakes would come from the journal itself.

UPDATE 3: 6/12/14.

Kritina Fiore has fixed the Medpage article.  Nice.

UPDATE 4: 6/12/14.

Science Magazine gets the causation vs. correlation issue wrong in their little news piece about this.  Yuck.


UPDATE 5: 6/12.

Alexandra Sifferlin has a good article about this at Time




More accurate coverage by Claire O’Connell in the Irish Times Generally a good article here: Rugby players show good guts


Popular Science messes it up too


Keeping track of some of the Tweets about this on Storfy.

UPDATE 9 6/13/14.

NPR News Falls for the Hype


UPDATE 10: 6/13/14.

Just found another inaccurate claim in the original paper

UPDATE 11: 6/13/14

Oh FFS. Now I have found some articles reporting not only that exercise affects gut microbial diversity but that this is why exercise reduces obesity. See Exercise lowers obesity risk by stimulating diverse gut bacteria in the NVO News, for example.


Quote from the story:

A latest research suggests that exercise actually lowers obesity risk by stimulating diverse gut bacteria

UPDATE 12: 6/13/14

Fox News did better with the science (at least in their headline) than many other News Agencies (and much better than NPR).  They report “Exercise may lead to healthier gut bacteria“.

Just that word “May” makes me happy.  I know.  Low bar.  But I will take what I can get.

UPDATE 13: 6/13/14

Genome Web also is reporting on the story and on the “overselling” that was done.

UPDATE 13: 6/18/14

And now the New York Times joins the fray: Exercise and the ‘Good’ Bugs in Our Gut where Gretchen Reynolds writes:

The findings suggest that, in addition to its other health benefits, frequent exercise may influence our weight and overall health by altering the kinds of organisms that live inside of us.

No – the findings do not suggest that.  The findings are consistent with that theory but they are consistent with many many many other theories.  FFS this is maddening.  And the article ends with a quote from one of the authors:

But even in advance of those findings, he said, it seems likely that any amount of exercise should make your gut more welcoming to the bacteria that you want residing there.

I note – I found out about this article via Twitter


No overselling here – Martin Blaser on the Daily Show discussing Missing Microbes and the human microbiome

Martin Blaser does a good job on the Daily Show discussing the human microbiome and his new book Missing Microbes.

Overselling the microbiome award: Time Magazine & Martin Blaser for "antibiotics are extinguishing our microbiome"

Well, alas, Time magazine turned what could have been a story about the spread of antibiotic resistance into what appears to be a promotion for Martin Blaser’s new book: Antibiotic-Resistant Bacteria Are Now In Every Part of the World |

The article starts of OK – reporting on the new WHO report on antibiotic resistance.  But then it gets into the microbiome and what antibiotics supposedly do to it.  Some quotes:

“But even more concerning, say experts like Dr. Martin Blaser, director of the human microbiome program at the New York University Langone Medical Center and author of Missing Microbes, is how these antibiotics are affecting the makeup of both good and bad bacteria that live within us – our microbiome. The first big cost of antibiotics is resistance,” he says. “But the other side of the coin is [the fact that] antibiotics are extinguishing our microbiome and changing human development.

Extinguishing our microbiome?  Really?  The evidence simply does not support such a claim.  I personally think antibiotics may be contributing to messing up the microbiome in many people and that this in turn might be contributing to the increase in a variety of human ailments (e.g., I mentioned this issue in my TED talk and many many times here and elsewhere).  But “extinguishing”?  Not even close.  In fact, many of the published sutdies done so far suggest that the human microbiome is pretty resilient in response to antibiotics.  Really serious overselling of the impact of antiobitcs by Blaser.

And “changing human development?”  Not sure what the evidence for that is either.  Most likely this refers to the role the microbiome plays in immune system development but I am not aware of strong evidence that antibiotics lead to changes in human devleopment.

They then quote Blaser again:

If I prescribe a heart medicine for a patient, that heart medicine is going to affect that patient,” says Blaser. “But if I prescribe an antibiotic, that antibiotic will affect the entire community to some degree. And the effect is cumulative.

Yes antibiotics can affect more than one person because microbes (and resistance) can spread.  But “the effect is cumulative”?  I do not think that has been shown.

Finally, Time (well, Alice Park, the author) states (in relation to limiting overuse of antibiotics)

That may also help to protect our microbiomes, which in turn could slow the appearance of chronic diseases such as obesity, cancer and allergies.

What?  Now antibiotics cause obesity?  And allergies?  And cancer? Sure – there is good reason to think that antibiotic usage plays a role in obesity and allergies.  The evidence is not yet completely overwhelming but it is certainly a reasonable notion.  But how did cancer get thrown in here?

I note – as I assume many know – I think the microbiome is critical to many human functions and phenotypes.  And screwing with it via excessive use of antibiotics seems like a very very bad idea.  The precautionary principle says to me we should avoid any antimicrobials unless absolutely necessary.  But do we really need to overstate what we know in order to effect change?  Do we need to say things like “antibiotics are extinguishing our microbiome” which is simply untrue?  I don’t think we do.  I think we can be more careful, not mislead people, and still have an impact.  And thus, I am giving out today’s “Overselling the microbiome” award to Time magazine and Martin Blaser.

UPDATE 5/1 – some links of interest

Other Overselling the Microbome Awards:

Some papers of relevance on antibioics and the microbiome

Ancestral human microbiome

UPDATE 5/3/4

Some papers that offer a more tempered view of the role of the microbiome in causing various disease:

  • Disturbed gut colonisation patterns have been associated with allergic disease, but whether microbial variation is the cause or effect of these diseases is still under investigation. We are far from understanding what constitutes a “healthy gut microbiome” that promotes tolerance. This remains a major limitation and might explain some of the inconsistency in human intervention studies with prebiotics and probiotics. Multidisciplinary integrative approaches with researchers working in networks, using harmonised outcomes and methodologies are needed to advance our understanding in this field.
  • Such data suggest that bona fide associations may exist between microbiota and obesity in humans, although causality remains to be addressed. Whether these associations will hold up to large-scale replication has yet to be determined. This situation is reminiscent of genetic association studies done in the pre-genome-wide association scan era, during which many candidate associations were found using sample sizes which at the time were considered large, but were rather small in retrospect [54]. Very few of these earlier associations have held up to replication in the modern era, where the threshold for association is more stringent and requires sample sizes orders of magnitude larger [55]. It seems reasonable to postulate that causal contributions from the gut microbiome to the development of human obesity have effect sizes on the order of common genetic variations implicated in complex diseases. If this is the case, much larger studies will be necessary before we have clear evidence of association.  
  • This review considers the nature of the evidence supporting a relationship between the microbiota and the predisposition to disease as associative, correlative, or causal. Altogether, indirect or associative support currently dominates the evidence base, which now suggests that the intestinal microbiome can be linked to a growing number of over 25 diseases or syndromes. While only a handful of cause-and-effect studies have been performed, this form of evidence is increasing. 
  • Talk by Rob Knight on “From Correlation to Causation in Human Microbiome Studies”

Update 5/4 #2.  I would also recommend people check out the Helicobacter foundation web site. which has some useful background information on the organism and the diseases it causes.

Update 5/4 #3.  Some recent papers by Martin Blaser worth looking at

UPDATE 5/4/#4. Martin Blaser on Dr. Oz show where Dr. Oz and Blaser both make some statements that are a seriously over the top.

History of studies of the affect of antibiotics on human health

Oh – and Barry Marshall – winner of the Nobel Prize for discovering how H. pylori causes ulcers and cancer – chimed in on Twitter:

// Other Tweets of relevance






UPDATE 5/4 – Caesarian Section Risk notes

A related question I have been thinking about involves Caesarian sections and whether they lead to an increased risk of any ailments that might have a microbial connection (e.g., obesity, allergy, autoimmune diseases). I started digging into the literature on this for my TED talk and then again when I posted something from the Smithsonian Genomics Exhibit that suggested there were no risks associated with C-sections.

Some papers on the topic suggest there may be some risks from C-sections related to these topics but that they are very very small:

UPDATE 5/5 Diabetes

Increase in type 1 and type 2 diabetes rates in children reported – is this connected to antibiotic usage or microbiomes?

Human microbiome story of the month: OpenBiome fecal bank for fecal transplants

Wow – fascinating story by David Glenn in the Chronicle of Higher Education: Student-Led Project Banks on Promise of Fecal Transplants – Research – The Chronicle of Higher Education.  The article tracks the story of Carolyn Edelstein and Mark B. Smith and James Burgess who have created a feces bank called OpenBiome to provide materials for fecal transplants.

Some related posts of mine:

Simple but important paper on the personal microbiome

Figure 1.

Quick post.  Just saw this paper:

PLOS ONE: The Personal Human Oral Microbiome Obscures the Effects of Treatment on Periodontal Disease:

Schwarzberg K, Le R, Bharti B, Lindsay S, Casaburi G, et al. (2014) The Personal Human Oral Microbiome Obscures the Effects of Treatment on Periodontal Disease. PLoS ONE 9(1): e86708. doi:10.1371/journal.pone.0086708

It has multiple things of interest (certainly to me – as we are doing some work on the oral microbiome). But I do not have time right now to dig through all of it.  I want to just point out one very important line in it:

Our results highlight how understanding interpersonal variability among microbiomes is necessary for determining how polymicrobial diseases respond to treatment and disturbance

This is consistent with what has been a gut feeling of mine (and something I say in lots of interviews and talks) but for which I did not have any obvious citation in mind.  Now I do.

Quick ego-post – link to interview of me by National Geographic Weekend show

Quick post here.  Was interviewed for National Geographic Weekend by Boyd Matson a few days ago and the show was just posted online: January 19, 2013: Waging War Against Whalers, Paragliding Above Pakistan and More – News Watch.  Scroll down to find the link to my part ..

Possibly interesting new microbiome study but can’t get past misleading quote

Just got done reading: Restoring helpful bacteria of the gut and intestines may treat patients with RCDI, find scientists.  A lot in the story is interesting.  And it discusses work by friends / colleagues of mine.  But I just don’t feel like writing about the work because the end of the article rubs me the wrong way.  Here is the whole paragraph that bothers me:

“This study helps underscore the importance of the microbiome in maintaining health and demonstrates that good bacteria play an integral role in immune defenses against disease,” says E. Albert Reece, M.D., Ph.D., M.B.A., Vice President for Medical Affairs at the University of Maryland and the John Z. and Akiko K. Bowers Distinguished Professor and Dean of the University of Maryland School of Medicine. “These findings also provide a potential therapeutic model for other diseases that have been linked to changes in the human intestinal microbiota, such as obesity and diabetes.”

What is wrong with this?  Well, #1 – the 1st sentence implies a bit too much to me that this study is novel in demonstrating that “good” bacteria play a role in immune defense.   When of course this has been shown for many many years.  But let’s let that slide.  Not a big deal.

It is the last line that irks me:  “These findings also provide a potential therapeutic model for other diseases that have been linked to changes in the human intestinal microbiota, such as obesity and diabetes.”

Hmm.  Obesity and diabetes in humans have not been shown to be caused by changes in the microbiome.  And therefore it is inaccurate to imply that one could take the fecal transplant for C. difficile model (which is what this current work is about) and extended it to obesity and diabetes.  You could say he is careful with words here by saying “linked to” not “caused by” but I think the clear implication here is that he is promoting fecal transplants as a therapy for obesity and diabetes.  And he should be more careful (especially as Dean of the University of Maryland School of Medicine).  I beg of people out there.  Please please please.  Microbiome studies have enormous potential.  In so many areas.  But we risk turning microbiome work into the next medical snake oil if we are not careful with our words.

Mini journal club: staged phage attack of a humanizes microbiome of mouse

Doing another mini journal club here.  Just got notified of this paper through some automated Google Scholar searches: Gnotobiotic mouse model of phage–bacterial host dynamics in the human gut

Full citation: Reyes, A., Wu, M., McNulty, N. P., Rohwer, F. L., & Gordon, J. I. (2013). Gnotobiotic mouse model of phage–bacterial host dynamics in the human gut. Proceedings of the National Academy of Sciences, 201319470.

The paper seems pretty fascinating at first glance. Basically they built on the Jeff Gordon germ free mouse model and introduced a defined set of cultured microbes that came from humans.  And then they stages a phage attack on the system and monitored the response of the community to the phage attack.

Figure 1 from Reyes et al.

They (of course) also did a control – in this case with heat killed phage.  And they compared what happened to the live phage.  I love this concept as they are able to control the microbial community and then test dynamics of how specific phage affect that community inside a living host.  Very cool.

Overselling the microbiome award: VIB press release saying "Intestinal flora determines health of obese people"

Some really cool new papers are out on the human microbiome today.  But alas that is not what I am here to talk about.  I am here, once again, to complain about overselling the microbome.  There is a headline from a press release from one of the institutes involved in one of the new studies that really irks me: “Intestinal flora determines health of obese people“.  As far as I can tell from reading the paper under discussion in this PR, nothing showed that the flora “determined” the health of obese people.  Yes, the flora had really interesting correlations with health status.  But “determines health” implies that the flora were the causal component of the health of obese people.  And as far as I can tell this was not shown.  What was shown was that the microbial communities – and some metrics of those communities like richness – can help predict risk of individuals for various health related ailments.

Now, mind you, the person discussed in this PR Jeroen Raes is completely brilliant and one of my favorite people in science in many ways.  And also it is important to point out that the paper does not make these claims.  The paper says things like

Our classifications based on variation in the gut microbiome identify subsets of individuals in the general white adult population who may be at increased risk of progressing to adiposity-associated co-morbidities

Even the title:

Richness of human gut microbiome correlates with metabolic markers

So – the reviewers and the authors seemed to have been relatively cautious in the text of the paper.  And the paper is fascinating and filled with important details.  But the headline in this press release has the potential to do damage to the whole field – especially as it gets taken up by the press.  And that is a shame.  The human microbiome is clearly important.  Why oversell it with BS like this?

Thus I hereby award an “Overselling the microbiome award” to the VIB Institute for their press release.

From the VIB Home Page

UPDATE 8/29 7:30 AM.  See comments.  Author Jeroen Raes gets PR fixed …

UPDATE 8/29 9:50 AM. Some links of interest