Microbiota, the intestinal revolution. © INRA

Microbiota, the intestinal revolution

A new dawn for medicine

Human intestinal microbiota, the new organ that has not yet revealed all its secrets to doctors, has an impact on health. The question is, how so? Researchers are busy analysing the dialogue between intestinal bacteria and human cells the better to understand its impact on inflammatory, metabolic and neurological disorders. The possibilities for research are endless. They will probably lead to a better grasp of what makes individuals sensitive to a given medical treatment or a pathogen, and a better understanding of the link between diet and health. These studies are opening new doors to new drugs, new diets, more personalised therapies, and even preventive medicine.

Updated on 04/28/2017
Published on 02/16/2017

Protein sequences on a computer screen.. © INRA, Bertrand Nicolas
Protein sequences on a computer screen. © INRA, Bertrand Nicolas

Manufacturing missing bacteria

Diabetes, inflammatory disease, intestinal disorders… it is now well known that the absence or excess of certain bacteria provokes imbalances that cause or exacerbate certain disorders. And since these bacteria are rather sensitive to oxygen, the challenge will be to produce them at industrial level and make them available to patients in powder form (sachet or capsule). Researchers have already identified about a dozen bacterial species that are known to have health benefits. They have access to collections of strains that they can therefore mass produce and run clinical tests on with patients. These harvests are currently being prepared. Clinical tests started in late 2016 and several others are in the preparatory phase

FOR PATIENTS WITH METABOLIC DISEASE OR DIABETES / Akkermansia muciniphila is a bacteria that has a significant effect on intestinal permeability. It reinforces cohesion between human cells of the intestinal wall and decreases the passage of bacterial signals. In doing so, it also protects against intestinal inflammation, which induces resistance to insulin and diabetes. Its effects have been shown beyond the shadow of a doubt, and scientists are trying to regulate its presence through diet. When the bacteria are totally absent, the scientists will try and deliver it directly to a patient to see if it fights diabetes. Tests are currently being carried out in Belgium.

TO TREAT INTESTINAL INFLAMMATORY DISEASE / Today in France, researchers are trying to make a complete transplant of intestinal content. A key bacteria has been identified at INRA: Faecalisbacterium, which is well-known for its anti-inflammatory effects. The next step has already been taken, to mass-produce the bacteria at industrial level. The bacteria will be administered in capsule form to patients to alleviate inflammation, or (and this is where things get interesting in inflammatory disease) prolong the quiescent (or dormant) phases of the disease. The quality of life of these patients with an incurable disease should see a big improvement.

CONCERNING INTESTINAL FUNCTION DISORDERS / 15% of the world’s population suffer from intestinal disorders, a whopping figure that has caused pharmaceutical laboratories to listen up. To keep intestinal disorders in check, the bacteria Blautia hydrogenotrophica is being manufactured and results so far have been promising. 

The therapeutic use of these bacteria is a scientific breakthrough that dates to less than five years ago. Tests are being carried out in man, and this is opening doors to new drugs that contain living and intact bacteria.

New ways of preventing and curing disease

Laboratory equipment of the quantitative metagenomic platform (MICALIS-MetaGenoPolis).. © INRA
Laboratory equipment of the quantitative metagenomic platform (MICALIS-MetaGenoPolis). © INRA

With human gene sequencing came the identification of genes that predispose people to disease. In studying the major ailments of modern societies, science has found, on the one hand, that they involve more than a simple pathogen, but an overall imbalance in the host-microbiota relationship. On the other hand, human genes are often only a minimum-risk factor. Genetics only explain, at best, between 5 and 10% of causes of illnesses today, even when a large number of predisposition genes accumulate. However, analyses of microbiota genes allow scientists to make precise correlations between these illnesses and the presence of certain microbial genes. As a result, medicine and nutrition must acknowledge and take into account the fact that man and his microbiota are in symbiosis, and that this symbiosis is key to maintaining health and well-being. The tide is already changing in this direction. Today, scientists are bringing patients the fruit of their research, which will change the face of medicine. We are now entering an era of new knowledge, where the metagenomic profile of each individual will generate gigabytes of medical data to boost diagnoses and treatments. With the microbiota under scrutiny, a “revolution” is underway in the fields of preventive nutrition and medicine.

Disease caused by ticks: blame the microbiota?

Female Ixodes ricinus (species of tick) and her eggs.. © INRA, Vectotiq
Female Ixodes ricinus (species of tick) and her eggs. © INRA, Vectotiq

Ticks are the number one vector of animal disease in the world, beating even mosquitos. Indeed, these mites have the nasty habit of transmitting a number of diseases to animals, and especially to man, including borreliosis and Lyme disease. For several years now, scientists have been turning their attention to the microbes involved in their modes of transmission. At the forefront of European research, INRA researchers have notably analysed the mode of transmission, pathogenic agents transmitted, and almost the entire make-up of tick microbiota. Today, research is focussed on how the microbiota influences the transmission of pathogens and the development of highly effective diagnostic tests. The goal is to detect pathogens and be able, in future, to modify the composition of tick microbiota to eliminate disease-causing agents. It is worth noting that almost 30 diseases in Europe are caused by bacteria, viruses, or parasites borne by ticks. For now, only Lyme disease has been diagnosed, and remedies exist. But science is in the dark about many other diseases. In order to move away from the “one disease, one pathogen” paradigm, INRA is actively looking for - notably through the project “Oh! Ticks” which was launched in 2016 - all the correlations between the different players in tick microbiota in what is called the “pathobiome”, that is, a pathogen in its biotic environment. The on-going genetic sequencing of tick microbiota is slowly revealing its secrets. When can the world expect a complete diagnosis of all of the diseases transmitted by these nasty hosts?