an alternative to antibiotics produced by bacteria in the intestinal microbiota ⋅ Inserm, La science pour la santé

Bacteria naturally present in our intestine seem to produce substances capable of inhibiting the growth and virulence of certain salmonellae. Identifying these compounds could pave the way for the development of an alternative to antibiotics.

Salmonellosis is a generally food-borne infection, responsible for abdominal pain, diarrhoea, nausea and sometimes severe vomiting. It is caused by bacteria from the Salmonella family that manage to cross the intestinal barrier. Among them, Salmonella Heidelberg (S. Heidelberg) has the particularity of presenting many resistances to antibiotics, so that alternatives to the latter would be useful in the management of infected patients. One of the avenues envisaged is to resort to probiotics : these bacteria beneficial to our health indeed produce metabolites which could fight against certain intestinal pathogens. At the Numecan Institute in Rennes, Latifa Bousarghin and her team studied the properties of Bacteroides fragilis (B. fragile), a bacterium from the Bacteroidota family − the most abundant in the intestine − which helps maintain the balance of the microbiota. ” In previous studies, we have shown that the presence of B. fragile reduces the ability to S. Heidelberg to cross the intestinal barrier in mice. We continued this work to understand the mechanisms responsible for these properties. “says the researcher. In collaboration with Sophie Tomasi of the Rennes Institute of Chemical Sciences (CNRS unit 6226), she has worked on the identification and characterization of compounds secreted by B. fragile which are at the origin of the anti-infective effect observed.

From a mixture of compounds to active molecules

This work is carried out from B. fragile cultured in the laboratory, or more exactly from their culture supernatant − the liquid medium in which bacteria multiply in vitro and where we find the metabolites they secrete in their environment. Given the richness of this supernatant, it was first fractionated to separate the compounds that are close from the physico-chemical point of view. Six different fractions were thus collected, then individually brought into contact with S. Heidelberg. Two of them were able to inhibit the growth of the pathogenic bacteria. Administered to infected mice, these same fractions reduced the inflammatory reaction at the intestinal level and reduced the ability of the pathogen to cross the intestinal barrier.

The work of identifying the bioactive compounds was then initiated. Two of them were easy to recognize because they are naturally present in the bile juices produced by the liver: cholic acid and deoxycholic acid. ” We already know that, taken in isolation, these two bile acids have no proven antibacterial action. in vivo. They probably need biological cofactors to be active against S. Heidelberg”, explains Latifa Bousarghin. The researcher is therefore continuing the chemical analyzes to discover the nature of the other potentially active molecules. “We will then test each of the identified compounds, individually or mixed in small numbers, to determine which ones are of interest. »

A track for several clinical developments

Other ongoing experiments aim to determine whether these metabolites are active against other bacterial species that are pathogenic for humans or animals. Finally, ” analyzes carried out in mice have shown that these same supernatant fractions have an impact on the bacteria of the intestinal microbiota which are known to be associated with diseases such as anxiety or depression… “. These results pave the way for further work in this area.

« Antibiotics directly block certain important pathways of bacterial metabolism, but the stress generated is such that it promotes the development of resistance to these antibioticsrecalls the researcher. The approach probiotic is different.B. fragile or its metabolites do not attack the bacterium, but rather the way in which it interacts with the cells of the host. This makes it possible to regulate its virulence more finely, and probably reduces the risk of seeing resistance develop. With the help of Inserm Transfert, his team filed a patent for the use of B. fragile to fight against certain bacterial infections: an approach that will make it possible to envisage the clinical development of this approach when the preclinical data justify it.

Latifa Bousarghin is a teacher at the University of Rennes and a researcher in the unit Nutrition metabolisms and cancer