Seth Bordenstein, Joël Doré, Paul Enck: a three-voice debate about gut microbiota research

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Every technical revolution generates a first wave of enthusiasm and everyone is willing to “play” with the new tool, hoping to find the Holy Grail. That had been already observed when Watson and Crick discovered DNA. Where are we, after the recent revolution of the discovery that we are made of one part of human cells and nine parts of microbial cells? How does this notion of a so-called new/neglected “organ” is impacting science and medical practice?

With more than 2000 scientific publications issued in little over ten years, no one can doubt that gut microbiota is a booming area of research. However, there is an existing dose of skepticism around some of the microbiota-related studies results. While from an epistemological perspective some experts believe that this is just part of the normal evolution of a new science or area of research, others believe that the news is overpromising or just exaggerating the results. The potential areas of interest around the science of microbiota are increasing and, at the same time, there are some pragmatic questions around how (and when) these discoveries would impact everyday practice. As a platform dedicated to sharing information about gut microbiota, we have decided to address this topic and, in order to do so, we interviewed three experts from this field who have different views.


 

Seth R. Bordenstein, Associate Professor of Biological Sciences and Pathology, Microbiology, and Immunology at Vanderbilt University, Nashville. He is a scientist, educator, communicator and consultant. This is his blog, and you can also follow him on Twitter.

Joël Doré, Head of Research at the Ecology and Physiology of the Digestive System Unit at INRA (the French National Institute for Agricultural Research). He also worked for the MetaHit European project and is Head of the Scientific Board of Gut Microbiota for Health Experts Exchange. You can follow him on Twitter.

Paul Enck, Professor of Medical Psychology and Director of Research, Department of Psychosomatic Medicine at Tübingen University in Germany. He is member of the Board of Gut Microbiota & Health Section of the European Society of Neurogastroenterology & Motility (ESNM) and of our Editorial Board.

 


 

How do you explain what is happening around the research into microbiota? Is this part of the normal evolution of a new science or just an exaggeration of the results?

Bordenstein: Biology has entered a new era with the capacity to understand that an organism’s genetics and fitness are inclusive of its microbiome. As a result, animals and plants are rightfully being heralded today as no longer individuals, but rather metaorganisms or holobionts composed of the essential genes in the nuclear genome, organelles, and microbiome. This newly appreciated knowledge is causing a revolution in the life sciences as we gain an increasing appreciation of what defines our health and fitness. History tells us that new sciences, especially those that have the potential to reorient subdisciplines, will struggle with terms, inferences, and intellectual prejudices. Microbiota research is certainly no exception and thus the tug of war between skepticism and insight is a vibrant sign of a healthy scientific discourse. All voices are welcome at this nascent beginning. The process will ultimately correct itself as it always has.

 

The tug of war between skepticism and insight is a vibrant sign of a healthy scientific discourse

Seth R. Bordenstein

Doré: Gut microbiota has benefit for an increasing interest during the last years and I see two main reasons for this. On one side, the development of new technologies that have allowed the sequencing of this “second genome”, the intestinal metagenome (70 to 80% of which is not suitable for culture). On the other, an increasing recognition of the link between gut microbiota and most of the major diseases linked to modern society, whose prevalence has been rising since the second half of the last century.

Enck: Looking over more than 30 years of science development in medicine and related issues, I must say that the current situation with respect to gut microbiota research reception in the general public (not in science) is unusual and by no means normal, but not without other examples (it reminds me of the euphoria at the beginning of the human genome projects). What is obvious is the dramatic difference between the complexity of the microbiota research (that allows fewer and fewer scientist to fully understand the latest progress and makes them dependent on system biologists and statisticians) on the on hand, and the simplicity of the results of this research that is transmitted to the general public (mostly by bloggers, journalists, and the media). What I assume is that both trends are complementary: the less we understand, the simpler the interpretation becomes. And since this development is related to an issue that everybody is interested in (i.e. healthy nutrition) the messages that are generated are rapidly perceived and adapted by the general public: healthy food for a healthy life (to cite a popular EU research topic).

 

In your opinion, what are the most common mistakes made when presenting the results from research or when extracting conclusions from them?

Bordenstein: Mistakes are actions or conclusions that are misguided or wrong; the peer review process should take care of most of this. That being said, the microbiome sciences are evolving quickly and the community is looking for leadership in best standards and practices. There are a myriad of ways to analyze microbiome data, and investigators cannot simply rely on their research core to produce the best data. That would most definitely fall in the mistake category, and I’ve seen it first-hand. Recognizing that labs doing microbiome projects must be well-versed and hands-on in the big data analyses is key to avoiding mistakes. Other concerns involve attention to experimental design such as appropriate sample sizes, replication, and negative controls.

Doré: I can see two major mistakes. On one hand, we suffer from a lack of standards which complicates the comparison of results. This is emphasized by the fact that technologies are spreading and becoming accessible to colleagues who do not necessarily have the background and expertise to interpret them. Another mistake is that microbiota is not alone; it is interacting with the host from birth on. For instance, dysbiosis which has long been presented as a distortion of microbiota, should be seen as an alteration of man-microbe symbiosis…

 

it will take another 10 years or more to get to the point that we can separate the relevant and irrelevant data for human health

Paul Enck

Enck: There are two basic mistakes that I see. One is overstating and over-interpreting animal data as relevant for human health, human nutrition and human diseases. Scientists are aware of it but journalists often do not even recognize whether this is animal or human data. The second mistake is one at least in part generated by the scientists themselves: Because of the complexity of the topic “microbiota and health”, we tend to simplify the messages, to get information across. One reason for doing so is that this research (as was the past endeavor to unravel the human genome) is expensive and requires additional public justification; the other is that expensive research appears to need media support because of limited monetary resources available and the competition between demands from different branches of the scientific community.

 

Is the microbiome science already impacting the daily practice of doctors and researchers? And what about the rest of the society, is this information changing lifestyle habits or nutritional choices?

Bordenstein: The science of the microbiome has caused some significant changes in society. First, just as one looks to the stars to understand our place in the universe, looking inside to our microbes has guided an appreciation that our species, Homo sapiens, is not special, but rather depends upon numerous other microbial species as well. Second, the resounding success of fecal transplants and spread across clinics is a testament to the microbiome health applications. By all accounts, this trend will continue.

Doré: Not yet. It takes translation and translation very often takes patents and products. In the medical arena, there are diagnostic and prognostic kits that are soon to come and medical products based on what Dr Martin Blaser calls ‘missing microbes’. In nutrition, probiotics were fairly popular in Europe until EFSA took over and now we do miss a proper mechanism of regulatory validation of scientifically proven benefits such that the support chain from science to consumer is broken. Until this is set back to normal, we can hope that recommendations make their way through to the society but channels are weak.

Enck: Definitively not, neither for doctors nor for the general public, eventually for science. I also do not see that nutritional habits and choices have changed much. And if I might guess, it will take another 10 years or more to get to the point that we can separate the relevant and irrelevant data for human health that is collected currently in science.

 

What is the role of press officers and science journalists in this scenario?

Bordenstein: The role of press releases and journalism on the microbiome should be to captivate without capitalizing – to promote knowledge rather than make promises – to illuminate without immortalizing at this incipient stage of the science.

Doré: Science journalists have a major responsibility since they are the ones who provide information. They should help scientists and clinicians communicate what is sound and robustly demonstrated and emphasize areas where knowledge is weak or lacking so that society and consumers find appropriate support. Science journalists are also a major relay towards GPs and clinicians, together with web-based information sources such as www.gutmicrobiotaforhealth.com or this blog.

 

Science journalists should help scientists and clinicians communicate what is sound and robustly demonstrated and emphasize areas where knowledge is weak

Joël Doré

Enck: As mediators between science and the general public, science journalists should protect science from being mis- or over- interpreted, and they should protect the general public from being misinformed. Science needs time, and given the short period of time gut microbiota and health is on the agenda, we will need much more time to sort out whether (or not) the current research initiated a paradigm shift or a tempest in a teacup.

GMFH Editing Team
GMFH Editing Team