Can you tell us about your experience prior to Enterome?
PR: I worked for 14 years as a general practitioner, a family doctor and even as a country doctor. I think it’s worth mentioning because my interest for gut microbiota is based on my experience as a field doctor. This is what I call the “earthly approach to medicine”. I’m no researcher and to me it’s a critical element in Enterome’s philosophy. We put a lot of efforts in designing pragmatic solutions to answer simple questions: “what can we do in the interest of patients? How can we facilitate practitioners’ activity?” We are here to find medical applications further to INRA’s pioneering work on human gut metagenomics conducted by Dusko Ehrlich in the MetaHIT project.
Why does a general practitioner get interested in the gut microbiota?
PR: Actually I evolved in a world where the intestinal flora [as it was called at the time] didn’t exist! People viewed it then as a necessary evil, an intrusive element, a tolerated squatter… We knew floras existed all over the place i.e. on door knocks, in cheese…. but nothing specific was attached to the notion of gut microbiota. It was simply considered as the inevitable presence of bacteria.
Things changed in the early 80’s. I was a young doctor at that time. People started talking about the intestinal flora as a key element of digestive physiology. As microbiology techniques evolved, we started getting interested in various intestinal phenomena such as microbial diarrhea, the impact of the use of antibiotics… We were able to notice that the intensive use of antibiotics caused a complete disorder in the gut microbiota. When disrupted, we observed that several complications occurred: diarrhea, flatulence, colonization by opportunistic microbes… We understood that the gut flora existed by destroying it!
The end of the 80’s also marked the ability to develop molecular techniques, the early steps of culture-free microbial analysis. This happened thanks to Carl Woese’s description of 16S taxonomy.
As a consultant, I had the opportunity to work with French experts who were among the first describers of the gut microbiota. Finally I heard about INRA’s pioneer work and Dusko Ehrlich’s idea to do high throughput sequencing of the whole gut microbiota – what he called quantitative metagenomics. This was a real game changer in the microbiology world! The key of this revolution is that we understood that microbial genes are a major component of our organism.
Can you tell us about this change of attitude towards microbes?
PR: The idea that bacteria are our allies in health has not yet entirely reached the practitioners’ world. As far as I’m concerned, I believe that microbes are friends, not foes. And this belief is nothing new ; probably microbes were always considered as our friends. I see two major reasons as to why the 20th century deeply modified centuries of collaboration between us and our microbial companions:
1/ The invention of the fridge and its generalization in the 30’s is the first element. With this tool we were able to keep food in the cold in order to prevent the development of bacteria. It contributed spreading the idea that, since we were seeking to prevent bacterial development in food, it meant that all bacteria were bad for food. The invention of the fridge initiated a paradigm shift, in which bacteria were defined as the enemies of food. But that’s a complete historical and anthropological non sense.
The most striking is how fast this paradigm replaced centuries of microbial engineering for food conservation. Bacteria were precisely what helped humans store their foods. Surely the anthropological revolution in human development is, besides the discovery of fire and domestication of animals, the domestication of microorganisms. Salting and fermentation are good examples. With those food techniques come the inventions of cheese, dried meat, bread, beer…
In the 30’s, the paradigm changed completely: microorganisms became foes for food. Following this idea, we started producing sterile food. By doing so we actually enhanced food risk since it could now be colonized by any pathogen. Before the invention of the fridge, what we ate was based on the collaboration with microorganisms. Food is now no more protected by a natural flora. That can be called the hygienist shock.
This doesn’t mean that we shouldn’t have invented the fridge. Imagine a world where the fridge doesn’t exist. From a social organization perspective, it would be a terrible mess. But from a sanitary perspective, I believe we can genuinely ask the question. Fresh products are today not easily accessible without a fridge. So I would say that our fridge is necessary because of urbanization, not for sanitary reasons.
2/ The discovery of penicillin and its mass-production/-use after World War 2 is the second element that I think is key in the paradigm shift that occurred during the 20th century. Antibiotics were a great way to fight pathogens. But by using antibiotics, we started thinking that we should get rid of all microbes, good and bad bacteria alike. In the general public’s representation, microbes were associated with the image of the enemy. During the entire century, we had as a first reflex to destroy microbes. Only now do we re-discover that there is a potential in fighting bad bacteria using good ones.
I think our human destiny implies harmonious life with bugs. Microorganisms were on earth well before humans and we won’t be the ones to bring them down. We have to use them the same way they use us. Probably their evolution led them to take advantage of the emergence of animals to find a cozy habitat, with food regularly served, warmth and for some of them protection from daylight. Their interest for millions of years was to favor their hosts’ survival. I believe that a lot of our behaviors has to be governed by our inner inhabitants. We often assume that we’re the pilot of our own body, but it is thinkable that we are merely the vehicle! We should at least speak of a co-decision process.
I witnessed the accidents of antibio-therapy and the disasters of hygienism. For a practitioner like me, coming back to such a vital human/microbe collaboration after its constant fight in the recent past century is a main concern.
What is Enterome’s role in that respect?
PR: What strikes me most is that researchers are currently understanding how the gut microbiota contributes to our health beyond nutrition and digestion. This is the reason why after talking with Dusko Ehrlich in 2010, we decided to develop medical applications. The first applications that we imagined were linked to digestive functions. But Dusko told us that metabolic applications could be as relevant. We even discovered that we could someday imagine immunology and neurology applications.
Enterome wishes to lead 2 revolutions: use fecal matters for the benefit of our health and treat microbes as friends. Our activity is about stating the obvious: bringing to the market the ability to read people’s health status by analyzing a stool sample. What a simple idea! How can we have missed the point for so long? This product of the human body, which bears so much negative connotations, probably tells us more about people than any other body sample. This was absolutely unexpected. I spent my entire practitioner’s life making skin, blood, and urine samples without thinking about the most obvious. Everyday we flush in the toilet the most informative product of our body and the simplest to collect. Using a neglected body product contained a transgressive dimension that immediately appealed to my curiosity.
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[ABOUT ENTEROME]
Enterome is a privately owned stratified medicine company, dedicated to the development of innovative diagnostics products based on recent progress in metagenomics of the human intestinal microbiota.
Measurement and modulation of the gut microbiota’s role in health and disease presents the opportunity to impact medicine in an entirely new and unexplored way. Enterome’s technology was developed initially by Dusko Ehrlich within the INRA organization (French National Institute for Agricultural Research – Jouy-en-Josas, France). INRA’s leadership in the metagenomic field has led to create together with Enterome, Metagenopolis®, the most advanced and clinically validated biomarker platform to establish quantitative description of gut microbiota and correlations with disease phenotypes. Enterome’s objective is to develop, on the basis of our unique technology and know-how, innovative diagnostic that could enable clinicians to provide optimal care for their patients.
Enterome is advancing an internal pipeline of biomarkers in chronic serious diseases like metabolic diseases (NASH, obesity, type-2 diabetes); inflammatory bowel diseases (Crohn’s disease and ulcerative colitis); and central nervous system diseases (depression, multiple sclerosis, Parkinson, autism). These diseases share in common to be associated with perturbation of intestinal microbiota and to represent very large and mostly untapped pharmaceutical and diagnostic markets. For each of these development programs we have been already able to establish collaborations with renowned international KOL to access cohorts of patients.
