Missing Microbes – a review of Martin Blaser’s book on changing dynamics between bacteria and man

 

A bitter pill? (Photo by Flickr user timsamoff under a CC BY-ND 2.0 licence)

A bitter pill? (Photo by Flickr user timsamoff under a CC BY-ND 2.0 licence)

By Jonas Waldenström

As a species, we humans have radically changed our way of life in the last hundred years. Through modern medicine, better nutrition and improved hygiene we not only live longer, but also with less disease and pain. We are also becoming taller and fatter than our ancestors.

However, at the same time we see new ailments arising, like increased asthmatic problems, allergies, certain cancer types, and obesity, to name a few. And of course, the looming threat of resistant bacteria, or emergence of novel zoonotic pathogens is always there, just a monkey or a palm civet cat away. Plenty to do for future generation of physicians and microbiologists.

And for ecologists, too. Personally, I would go so far as saying that the merging of evolutionary theory and medicine is one of the most urgent needs for modern society. We need to understand that every treatment targeting microbes will be answered by an evolutionary response. Sometimes the response is rapid, as when a plasmid encoding antibiotic resistance is transferred between bacteria, and sometimes more slowly in changing pathogenicity or selection of increased virulence. The awareness is already here, at least theoretically, albeit not in function at the hospital floor (or in the food animal industry).

This summer I read a book with the title ‘Missing microbes – how the overuse of antibiotics is fueling our modern plagues‘. The author is Martin J. Blaser, a prominent scientist that has worked with pathogenic bacteria for decades. He is actually one of the founding fathers in Campylobacter and Helicobacter research.

It is a very interesting book, where Dr Blaser put his own research on bacteria in connection to the increasing incidence of modern diseases, such as obesity and asthma. It is not yet another book on antibiotic resistance. No, it is a book on what the consequences of reduced microbiological diversity imposed by antibiotics may have for our health.

The central tenet is that the widespread use of antibiotics (to treat infections, to produce food, etc.) is drastically altering our microbiome. If you are not familiar with the term microbiome, this means the whole assemblage of microbes that live and thrive in and on our bodies. The problem with antibiotics is that they hit rather bluntly. If the target is a pathogenic bacterium in your urinary tract, say an E. coli infection, the drug that is delivered to knock it out will also run rampage through your systems and kill a lot of more friendly by-standers. Collateral damage, in gangster terms.

The microbiome is entangled bank of microorganisms, a rainforest of bacteria and viruses. But it is not static; it changes in responses to our diet, exposure, hormonal levels, competition etc. Several of its constituents are doing good deeds for its host, for instance helping us degrading food items. Many have also been there for a very long time, evolutionary times. Plenty of time to develop symbiotic relationships.

Think of it, what is the first present your parents gave you? Was it a teddy bear? No, it was the microbiome of your mother, as you (a little fetus) were passing through the birth canal, and later when you started sucking on your mother’s breasts, and was kissed by your proud parents and relatives. These bacteria are the starting point of the next generation’s microbiome, inherited across generations from parents to offspring. Dr Blaser argues that we are interrupting these long-term evolutionary relationships between microbes and man. Caesarian cuts mean that the baby is not exposed to all of the microbiome of the birth canal, and frequent use of antibiotics over the course of a lifetime (and especially in the early months) come as sweeping scythes that may knock out certain species of the microbiome.

Some of these passengers may be good for us in ways we cannot phantom. One example Dr Blaser writes about is Helicobacter pylori. This bug has been perceived as a real bad guy. It lives in your stomach and may give you peptic ulcers and is associated with certain gut cancers. The response we have launched is to whack it out with a cocktail of antibiotics. Kill it, and you will be better off (for instance see this post). However, Dr Blaser has gradually come to a different view. In a series of experiments, his team and others have linked the absence of H. pylori to other sets of illness and disease, such as efflux and cancer in upper parts of the gastrointestinal tract. Maybe the bad guy isn’t all bad, maybe it is sometimes even beneficial? And is health really the absence of bacteria, maybe the presence of certain bacteria has the benefit of keeping the immune system primed?

He has also investigated the effects of antibiotic treatments on the microbiome in mice, and shown that treatment in a certain time period in early life affects not only which microbes that make up the microbiome, but also obesity status later in life. Thus, the microbes in our gut could affect our phenotype, all other things being equal (for a good resume of this see here).

I really recommend you to read his book – it is a fascinating story, written by an active researcher (which we tend to do too seldom). He launches some very interesting hypothesis that can be tested by laboratory and field studies. Read it and make your own interpretations.

 

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Not all birds are equal – a new paper debunks the notion of passerines as influenza A virus reservoirs

Influenza A viruses are elusive, just like the Scarlet Pimpernel - scientist seek them everywhere!

Influenza A viruses are elusive, just like the Scarlet Pimpernel – scientist seek them everywhere!

By Jonas Waldenström

In each scientific field there are findings that stand out as peculiar; odd findings that are not widely replicated. Still, as they are part of the scientific record, you need to relate to them in your own work, even cite them at times. For the influenza A virus field, one such oddity has been the detections of virus in passerines. A bird is a bird, you might say – so if ducks and other waterfowl are loaded with these viruses, why cannot other birds be infected?

However, birds cannot (and should not) be lumped together in a big pile just because they have feathers. Among the world’s 10,000 or so species there are both physiological and ecological differences – not to neglect millions of years of evolution. Thus, there are likely differences both related to exposure (geographical distribution, habitat preferences, behaviors, diet, etc.) and to susceptibility or pathogenesis (distribution of receptors and perceptive cell types, physiology of the gastrointestinal tract, immune responses, etc.) that govern how readily different bird species are infected. On top of this, the very methods we use to detect virus have their issues. It is not uncommon to have lab contaminations, especially of PCR-products, that can make the very sensitive RRT-PCRs say ‘bing’, when they should say ‘bong’.

This week, Morgan Slusher et al. in Georgia, US, published a comprehensive review of influenza A virus in passerines. Not only did they critically evaluate all articles reporting findings, they also conducted a large prospective study where they sampled and screened wild birds.

So what did they find? First of all, the review (in total 60 papers published up till 2012) revealed that the majority of virus findings in passerines were associated with outbreaks in domestic birds, or were from birds in periurban settings. Only few cases were described from wild birds in more natural settings. Furthermore, the authors identified a general lack of confirmatory proof, e.g. if samples were positive in a PCR screening there was no subsequent isolation (or sequence) of virus from those samples. Some papers were even pinpointed as potentially flawed, due to non-validated screening methods (nested PCRs that are prone to yield false positives) or to potential lab contaminants of viruses (where the same subtype was isolated in many samples collected from several locations, but processed in the same lab).

Second, the prospective screening of samples, both by RRT-PCR, isolation attempts, and an antibody-based ELISA, yielded very few positive signals. Actually, none of the birds tested by RRT-PCR (547 samples) or virus isolation (900) were positive, and only 3 out 3,358 tested with the ELISA method gave a signal for past infections.

The conclusions, at least to me, is that terrestrial passerines should not be considered as reservoir hosts. This is not the same as saying that they are never infected, but that in terms of influenza A virus epidemiology and evolution they are accidental hosts, often caused by spillover infections from infected poultry in connection to outbreaks. I think this is similar to what most influenza A virus ecologists thought already, but it is extremely important that a study such as this was published – again, because it becomes part of the scientific literature, and not just opinions of the individual researcher.

On a general note, I think this exemplifies how one needs to distinguish between different types of hosts. As most pathogens can infect multiple hosts, but with varying proficiency, a mere positive finding in a species should not be implied as that species is a functional host, or a reservoir. Most spillovers are dead-end infections, or result in short stuttered transmission chains. They should of course be studied – not the least because a pathogen may evolve better transmissibility in the new hosts – but some level of caution in language use is needed, as we otherwise give the wrong information about host range and epidemiology.

So, at last, let me paraphrase the Scarlet Pimpernel:

We seek it here, we seek it there,
Those Scientists seek AIV everywhere!
Is it in sparrows? Is it in trogons?
Where are those damn elusive AIV virions!

A Red-headed Trogon - not exactly a passerine, but it was the only bird to rhyme (although not great) with virion. Photo by JJ Harrison  [CC-BY-SA-3.0, via Wikimedia Commons].

A Red-headed Trogon – not exactly a passerine, but it was the only bird to rhyme (although not great) with virion. Photo by JJ Harrison [CC-BY-SA-3.0, via Wikimedia Commons].

Link to the paper:

Slusher, M.J., Wilcox, B.R., Page Lutrell, M., Poulson, R.L., Brown, J.D., Yabsley, M.J. and Stallknecht, D.E. 2014. Are passerine birds reservoirs for influenza A viruses? Journal of Wildlife Diseases, ahead of print.

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Invoices, badgers and elephants – I am back in the office

This was how I felt this morning. Photo from Flickr user generalising under a CC BY-SA 2.0 license.

This was how I felt this morning. Photo from Flickr user generalising under a CC BY-SA 2.0 license.

By Jonas Waldenström

Vacations are lovely, but the return to the office not quite so. It is nice to see all colleagues again and to chat about ideas and research. Have a coffee. Even fiddle with some manuscripts. But, academic life has not been put on hold in your absence, email by email your inbox has been filled with stuff that now craves for your attention.

During my holiday – a long Swedish 5 week summer holiday – I have got emails a plenty. Many of them, of course, the usual academic spam with ‘honorable speaker invitations’ and ‘esteemed professor, please publish with us’. This rubbish seems to escalate, as I get at least two such invitations per day – often from the so called predatory journals that just want a piece of my grant pie. (I have saved them for the last year, and will write a post about at some time)

There is also a certain category of emails, the invoices. Flash, flash, flash they come, first in yellow (meaning ‘not so urgent’) and then more intensely colored in red (meaning ‘deal with them now, or else…’). Oh joy!

Rembrandt's version of an elephant, from 1637 or so.

Rembrandt’s version of an elephant, from 1637 or so.

So what to do? Most of us just dig through the pile until it is gone. As the proverb goes: How to eat an elephant? Take one bite at the time.

But there are other ways.

A former professor at our department had his own administration technique. He simply put all stuff in a pile (this was when most things were still on paper, and not in digital format), pulled out his special ruler from the drawer and measured the height. If it were below 19.2 cm he let it rest, if it was above he would deal with it all. Quite genius and old school. I like it!

Another professor often marks all unread emails and simply press the ‘delete’-button. Done. A sort of momentary catharsis moment – from too much to do, to nothing. A clean sheet. Admittedly, this strategy has the occasional downside when an important email vanishes, but for the most part the really important stuff seems to be sent again.

But overall, it is good to be back. Tomorrow I will be full of energy, I promise. An alive and kicking badger. Time to submit those manuscripts. And write more frequently on this blog.

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