Efficacy of an inulin-based treatment on intestinal colonization by multidrug-resistant E. coli: insight into the mechanism of action

Abstract

Inulin, an increasingly studied dietary fiber, alters intestinal microbiota. The aim of this study was to assess whether inulin decreases intestinal colonization by multidrug resistant E. coli and to investigate its potential mechanisms of action. Mice with amoxicillin-induced intestinal dysbiosis mice were inoculated with extended spectrum beta-lactamase producing E. coli (ESBL-E. coli). The combination of inulin and pantoprazole (IP) significantly reduced ESBL-E. coli fecal titers, whereas pantoprazole alone did not and inulin had a delayed and limited effect. Fecal microbiome was assessed using shotgun metagenomic sequencing and qPCR. The efficacy of IP was predicted by increased abundance of 74 taxa, including two species of Adlercreutzia. Preventive treatments with A. caecimuris or A. muris also reduced ESBL-E. coli fecal titers. Fecal microbiota of mice effectively treated by IP was enriched in genes involved in inulin catabolism, production of propionate and expression of beta-lactamases. They also had increased beta-lactamase activity and decreased amoxicillin concentration. These results suggest that IP act through production of propionate and degradation of amoxicillin by the microbiota. The combination of pantoprazole and inulin is a potential treatment of intestinal colonization by multidrug-resistant E. coli. The ability of prebiotics to promote propionate and/or beta-lactamase producing bacteria may be used as a screening tool to identify potential treatments of intestinal colonization by multidrug resistant Enterobacterales.

Keywords: Escherichia coli; Inulin; intestinal colonization; microbiome; multi-drug resistance; prebiotics; resistome.

Figure 1.

Effect of inulin, pantoprazole and their combination on ESBL-E. coli fecal titers.

Figure 2.

Taxonomic diversity and architecture of fecal microbiome in mice effectively treated by inulin and pantoprazole in comparison with control or ineffectively treated mice.

Figure 3.

Preventive treatment with adlercreutzia caecimuris or adlercreutzia muris on ESBL-E. coli intestinal colonization.

Figure 4.

Metabolic pathways of fecal microbiota in mice effectively treated with inulin and pantoprazole vs control or ineffectively treated mice.

Figure 5.

Fecal β-lactamase activity, amoxicillin concentration and resistome in mice effectively treated by inulin and pantoprazole and in control or ineffectively treated mice.