Different antibiotics induce distinct dysbiotic states and grades of susceptibility to vancomycin-resistant Enterococcus (VRE) intestinal colonization.
a Schematic representation of the mouse model.
Mice were treated during seven days with antibiotics of different spectrum (i.e. ciprofloxacin, neomycin, ceftriaxone, ampicillin, clindamycin or vancomycin). Subsequently, a group of mice was orally gavage with 106 VRE colony forming units (CFUs), while another group of mice was allowed to recover for two weeks before VRE inoculation. Faecal samples were collected immediately before VRE inoculation for microbiota analysis and 2 days post-VRE inoculation (p.i). for quantifying VRE levels. As control, faecal samples were collected from a group of untreated mice for microbiota analysis and VRE quantification.
b Non-metric multidimensional scaling (NMDS) analysis based on Bray-Curtis distances obtained using the relative abundance of OTUs identified in faecal samples collected from mice. Each point represents the microbiota of one mouse.
Color legend is shown in (a) and indicates the antibiotic treatment received. c Heatmap that shows the abundance of the top 100 most abundant OTUs identified in the faecal samples collected. No treatment (NT), Ciprofloxacin (Cip), Neomycin (Neo), Ceftriaxone (Cef), Ampicillin (Amp), Clindamycin (Clin), Vancomycin (Van), Proteo (Proteobacteria). Taxonomy of the OTUs as well as statistical analysis of the OTUs abundance are indicated in Supplementary Data File 2. d VRE faecal levels (CFUs / 100 mg) 2 days p.i. in the mice receiving the different treatments. LOD = limit of detection. Points below the LOD indicate those mice in which we were not able to detect any VRE CFU. *p < 0.05, **p < 0.01, ns – nonsignificant, two-sided Wilcoxon rank-sum test. N = 5 mice per treatment except for ceftriaxone without recovery period in which N = 3 mice.
Statistical results shown in panel (d) refer to: above - the comparison of each treated group of mice with the untreated group; below: the comparison of each group of mice treated with a specific antibiotic (before vs after the recovery period).
In (d) boxes extend from the 25th to 75th percentiles. The line within the boxes represents the median. Whiskers indicate the maximum and minimum values. Source data are provided as a Source Data file.
Credit: Nature Communications (2022). DOI: 10.1038/s41467-022-35380-5
A study by the "Microbiota, Infection and Inflammation" research group at the Foundation for the Promotion of Health and Biomedical Research of Valencia Region (Fisabio), an agency of the Conselleria de Sanitat Universal i Salut Pública, has identified the ability of five bacterial strains of intestinal microbiota to restrict the colonization of bacteria resistant to multiple antibiotics.
This study, led by Dr. Carles Úbeda and published in Nature Communications, has revealed that in animal models, the consortium of bacterial strains of the genera Alistipes, Barnesiella, Olsenella, Oscillibacter and Flavonifractor—which are naturally present in the microbiota intestine—depletes the nutrients necessary for the growth of bacteria of the genus Enterococcus. These pathogens, which are multi-resistant to antibiotics, are especially affected by the loss of a type of sugar called fructose, which is commonly found in our diet.
In this way, the nutritional deficiency that pathogens encounter prevents their optimal growth and consequently protects the body against infection. "Using models with mice, we have shown that the administration of these commensal bacteria decreases the ability of the pathogen to colonize the intestine, a key step for the development of infection and transmission between patients," explained Dr. Úbeda.
These types of pathogens are among the third and fourth most prevalent causes of infections in hospitalized patients worldwide and can cause lethal outcomes due to their resistance to most currently available antibiotics, making treatment difficult. For this reason, it is among the highest priority multi-resistant pathogens for which new therapies must be developed, according to the World Health Organization (WHO).
To conduct the study, the research group of the Genomics and Health Area has applied novel techniques of mass-sequencing of bacterial DNA (metagenomics) and RNA (transcriptomics), as well as the analysis of substances called metabolites (metabolomics) present in the gastrointestinal tract.
This study could lead to new non-antibiotic-based strategies to prevent infections caused by this multi-resistant pathogen. "This is a significant discovery, because antibiotic resistance is one of the most important public health problems facing society today," concluded the researcher.
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