Microbiota and health: new therapeutic avenues

The intestinal microbiota -formerly called intestinal flora- occupies an important place in the health of individuals. Physician, holder of a doctorate, professor of nutrition at the University Hospital of Rouen in France, the D^r Pierre Déchelotte dedicates his research to this and directs the INSERM laboratory “Nutrition, Inflammation and Dysfunction of the Gut-Brain Axis”. We spoke with this internationally renowned researcher.

D^r Déchelotte, why is the intestine called the second brain?

If the gut is the second brain, the microbiota is the third brain. This third brain is located inside the second brain, and they both talk to the first one, the one above!

For about thirty years, we have shown that there are many neurons in our digestive tract, which explains why we spoke 20 or 25 years ago of the second brain. But it is even more complicated than that.

We are familiar with the cells that absorb food, but there are also many immune cells that play a role in regulating the intestinal barrier. There are endocrine cells that produce many hormones that play an important role in regulating hunger and satiety, but also in regulating motor skills and digestive sensitivity. All of these cell types communicate with each other.

This gut brain, therefore, must be understood as something more global.

He has studied eating disorders, in particular anorexia nervosa, in relation to the microbiota. Could the development of an eating disorder start from the microbiota?

Over the past 15 years, we have accumulated a whole series of publications that indicate that part of the maintenance mechanism, or even the triggering of anorexia, or perhaps other eating disorders such as binge eating or bulimia, could be linked to an imbalance in the microbiota . .

In fact, there is a dysbiosis, a significant imbalance of the microbiota, in anorexia nervosa. In bulimia, the data is still very limited, but we will soon publish new results. In binge eating, which leads to obesity, we are at the beginning of the story: our Belgian colleagues recently reported that the microbiota of compulsive patients is not the same as that of non-compulsive patients.

We have also done a lot of work on certain bacterial proteins that could regulate food intake.

His research was able to show that a strain of probiotics, now marketed in France, had a favorable effect on satiety and weight loss. Can you tell me more about that?

Within a few years, we were able to effectively demonstrate, first in animal models and then in a human clinical study, that the Hafnia alvei HA 4597 strain has a satiety-increasing effect and promotes weight loss in moderately overweight people .

However, it is not a treatment for obesity, but a food supplement that reinforces the natural mechanisms of satiety. We continue to search for other modulators of the microbiota that may be useful in nutrition. The Hafnia alvei HA4597 and Lactobacillus plantarum WJL strains (interesting for growth and renutrition) are already marketed in France and some European countries by our start-up TargEDys and the Biocodex laboratory. For the others, you will have to wait a little longer.

Can improving the microbiota contribute to the recovery of people who binge?

What we are currently saying in a patient with hyperphagia is that you first have to try to understand the mechanisms that led to the hyperphagia. They usually present great tensions, anxious-depressive disorders or other compulsive disorders. We will first treat the eating behavior with cognitive-behavioral therapies, with eating re-education and possibly with drugs, particularly serotonergics, such as fluoxetine and sertraline, which work quite well in compulsive disorders.

But not all patients respond to these relatively standard treatments. Therefore, it is also necessary to re-educate the microbiota, and the best re-education begins with food. If we manage to calm the compulsions, which are generally due to fatty and sugary foods, we will reduce the imbalance in the diet and gradually correct the dysbiosis. For example, by reducing sugars and fats, and increasing fiber, we will favor certain species, such as those that produce butyrate, and we will reduce a certain number of other species that depend on a massive intake of fats, and therefore, ultimately, we re-educate the microbiota first through food. But this is not always enough, hence the interest in a more direct intervention with certain very specific probiotics with evaluated efficacy.

You have just come from an international conference on prebiotics. What is new in this regard?

Precisely, the PROBIOTA 2022 congress, which has just been held in Copenhagen, brought together 400 researchers and industrialists from around the world to take stock of the latest advances. It is a field in strong expansion. Weight management remains a hot topic, and our work was the subject of a plenary conference, as were the fascinating developments by the team of Patrice Cani (Belgium) on Akkermansia Muciniphila, another strain that appears highly beneficial in reducing diabetes risk.

There were also many communications about the modulation of stress, anxiety, by the microbiota and certain probiotics. In short, the microbiota has not ceased to amaze us!

What do you think of the microbiota analysis kits?

Currently, what circulates as commercially available microbiota tests is not satisfactory. […] But this is a field that is changing very quickly, and a new generation of more advanced tests should soon see the light of day and, above all, better accompanied at a medical level. We are also working on it.

♦ To know everything about the microbiota, you can get hold of a collective work to which Dr.^r Déchelotte participated in addition to other European experts.

♦ Gut microbiota and human health Jean-Michel Lecerf, Nathalie DELZENNE Elsevier Editions