Elucidating the effects of selected antibiotics and artificial sweeteners on the intestinal microbiota and related fecal and plasma metabolome of young adult Wistar rats

Summary

Gut flora or microbiota play a vital role in maintaining host homeostasis. Bacteria, being the predominant species governing the gut microbiota are known to play a major role in the biotransformation of molecules that are obtained via host diet. In this project, we investigated the contribution of the intestinal microbiota to the formation of small molecules in young adult rats by inducing perturbations in the bacterial community by administering antibiotics and artificial sweeteners. Using metabolomics, we determined chemical induced changes in fecal and blood plasma metabolites and with a 16S marker gene sequencing method we determined the changes in intestinal microbiota composition. The 28-day oral administration of several antibiotics elicited significant alterations of key plasma biomarkers associated with a perturbed gut microbiota, including changes in bile acids, indole derivatives and hippuric acid.

One of the most abundant gut bacterial families, the Verrucomicrobiaceae, did not contribute to changes in any of the measured fecal metabolites. We observed spontaneous restoration of gut microbiota as well as metabolites post-doripenem antibiotic cessation within 7 – 14 days depending on the dose level. After 28 days of exposure of the rats to the artificial sweetener saccharin, but not upon exposure to acesulfame potassium, alterations in plasma bile acids were observed, without apparent changes in the gut microbiome. This may suggest a systemic effect or perhaps a subtle change in microbiota metabolic functionality.

Overall, the key findings of this thesis suggest that a combined analysis of microbiota and metabolomes is a suitable combination of technologies to elucidate gut microbial metabolic functionality and may be further considered for toxicological risk assessments of chemicals.