Antibiotic resistance in the gut microbiota

From a clinical point of view, colonisation with antibiotic-resistant bacteria refers to the identification of bacteria in a clinical sample that could be cultured ex vivo in synthetic medium enriched with antibiotics. Clinical samples of the gut microbiota could be obtained by taking a rectal swab or by collecting stool samples. Once exposed to aerobic conditions, most anaerobic bacteria die quickly, and only (micro)aerophilic bacteria as enterobacteriale continue to grow. These bacteria are also known as Cultivable Antibiotic Resistant Bacteria (CARB).

Such a biased perception of the colonisation of the gut microbiota with multi-drug resistant (MDR) bacteria is nevertheless associated with an increased risk of fatal infection. Infections due to MDR bacteria account for 55,000 cases each year in Europe. When cultured with antibiotic loaded discs, these bacteria express a typical phenotype of antibiotic resistance related to carbapenemase producing enterobacteriales (CPE), extended spectrum beta lactamase enterobateriales (ESBL), vancomycin resistant enterococci (VRE), expression ore derepression of Amp C beta lactamase. These phenotypes are associated with the expression of genes encoding enzymes, membrane modifying proteins or transporters. Bacteria could carry antibiotic resistance genes in their chromosome or plasmids, but only express the resistance factor under certain conditions. For example, most E. coli carry the antibiotic resistance factor AmpC at the DNA level, but only express the AmpC protein after being stressed by exposure to antibiotics. This makes the clinical use of stool DNA analysis insufficient to predict the antibiotic resistance profile of the gut microbiota reservoir.

Genes coding for antibiotic resistance are expressed not only in bacteria associated with human pathologies, but also in commensal bacteria, where they represent a pool of potentially transmissible factors of antibiotic resistance. This pool of genes encoding antibiotic resistance factors is called the resistome. The transfer of antibiotic resistance genes to other pathogenic bacteria or to commensals makes the resistome difficult to eradicate.

Repeated antibiotic treatment, prolonged stay in a healthcare setting or environmental colonisation with MDR bacteria are conditions associated with enrichment of the pool of genes expressed in the gut microbiota resistome. However, this condition is not sufficient and additional acquisition of virulence factors such as pili is required to trigger the pathogenesis of MDR bacteria, suggesting a functional role of the gut environment.

The development of new antibiotics active against MDR bacteria is limited, highlighting the need for alternative strategies to prevent the spread of MDR bacteria. Among these strategies, probiotic intervention on gut microbiota functions has been presented as an opportunity, supported by sparse in vitro and in clinical observations.


In a clinical study, we showed that treatment with probiotics during antibiotic therapy reduced colonisation by certain bacteria that are naturally resistant to antibiotics, such as Pseudomonas, but also increased the proportion of enterocbacteria expressing a resistance profile by expression of the beta lactamase AmpC.