Microbiota and health: new therapeutic avenues

The intestinal microbiota – formerly known as the intestinal flora – plays an important role in human health. Physician, PhD Professor of Nutrition at Rouen University Hospital in France, Dright Pierre Déchelotte dedicates his research to him and directs the INSERM laboratory “Nutrition, inflammation and dysfunction of the gut-brain axis”. We spoke to this internationally renowned researcher.

Dright Déchelotte, why is the gut called the second brain?

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

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

We know the cells that take in food, but there are also many immune cells that play a role in regulating the gut barrier. There are endocrine cells that produce many hormones that play important roles in regulating hunger and satiety, but also regulating motor function and digestive sensitivity. All of these cell types communicate with each other.

So this gut brain needs to be understood as something more global.

They have studied eating disorders, particularly anorexia nervosa, in the context of the microbiota. Could the development of an eating disorder come from the microbiota?

We have accumulated quite a number of papers over the last 15 years suggesting that part of the mechanism of maintenance or even triggering of anorexia or perhaps other eating disorders such as binge eating or bulimia may be linked to microbiota imbalance.

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

We have also done a lot of work on specific bacterial proteins that would be able to regulate food intake.

Their research showed that a probiotic strain now being marketed in France had a positive effect on satiety and weight loss. can you tell me more about it

In just a few years, we were able to show, first in animal models and then in a clinical study on humans, that the Hafnia alvei HA 4597 strain has a satiety-promoting effect in slightly overweight people and promotes weight loss.

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

Can improving the microbiota help people recover from binge eating?

What we are currently saying about a hyperphagic patient is that one must first try to understand the mechanisms that led to the hyperphagia. Often there are great stresses, anxiety-depressive disorders or other obsessive-compulsive disorders. We initially treat the eating behavior with cognitive behavioral therapies, with nutritional retraining and, if necessary, with medication, especially serotoninergics such as fluoxetine and sertraline, which work quite well in obsessive-compulsive disorders.

But not all patients respond to these relatively standard treatments. Therefore, there is also a need to re-educate the microbiota, and the best re-education begins with food. If we manage to calm the compulsions that are generally due to fatty and sugary foods, we reduce the nutritional imbalance and gradually correct the dysbiosis. For example, by reducing sugar and fat and increasing fiber, we will favor certain types, e.g. those that produce butyrate, and we’re going to reduce a certain number of other species that rely on massive fat intake, and so ultimately, we’re re-educating the microbiota through food first. However, 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 congress on prebiotics. What’s new about this?

In fact, the PROBIOTA 2022 congress that just took place in Copenhagen brought together 400 researchers and industrialists from around the world to take stock of recent advances. It is a rapidly expanding field. Weight control remains an important issue and our work was the subject of a plenary conference, as were the fascinating developments by Patrice Cani’s (Belgium) team on Akkermansia Muciniphila, another strain that appears to be very beneficial in reducing the risk of diabetes.

There have also been many reports of the modulation of stress, anxiety, by the microbiota and certain probiotics. In short, the microbiota has not surprised us yet!

What do you think of microbiota analysis kits?

What is currently circulating as a commercially available microbiota analysis is not satisfactory. […] But this is an area that is changing very quickly, and a new generation of more advanced tests and, above all, better accompaniment at the medical level should soon see the light of day. We’re working on that too.

♦ To know everything about the microbiota, you can get a compendium that Dr.right Déchelotte attended alongside other European experts.

♦ Gut flora and human health Jean-Michel Lecerf, Nathalie DELZENNE Elsevier editions

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