Impact of lincosamides antibiotics on the composition of the rat gut microbiota and the metabolite profile of plasma and feces
Behr, C. ; Ramírez-Hincapié, S. ; Cameron, H.J. ; Strauss, V. ; Walk, T. ; Herold, M. ; Beekmann, K. ; Rietjens, I.M.C.M. ; Ravenzwaay, B. van - \ 2018
Toxicology Letters 296 (2018). - ISSN 0378-4274 - p. 139 - 151.
Antibiotics - Gut microbiome - Metabolomics - Microbiome-related metabolites - Repeated dose oral toxicity study - Taxonomic profiling
The importance of the gut microorganisms and their wide range of interactions with the host are well-acknowledged. In this study, lincomycin and clindamycin were used to modulate microbial communities of Wistar rats to gain a comprehensive understanding of the implications of microbiome alterations. A metabolomics approach and taxonomic profiling were applied to characterize the effects of these antibiotics on the functionality of the microbiome and to identify microbiome-related metabolites. After treatment, the diversity of the microbial community was drastically reduced. Bacteroidetes and Verrucomicrobia were drastically reduced, Tenericutes and Deferribacteres completely disappeared, while abundance of Firmicutes and Proteobacteria were highly increased. Changes in plasma and feces metabolites were observed for metabolites belonging mainly to the class of complex lipids, fatty acids and related metabolites as well as amino acids and related compounds. Bile acid metabolism was markedly affected: taurocholic acid, glycochenodeoxycholic acid and cholic acid presented abrupt changes showing a specific metabolite pattern indicating disruption of the microbial community. In both plasma and feces taurocholic acid was highly upregulated upon treatment whereas glycochenodeoxycholic acid was downregulated. Cholic acid was upregulated in feces but downregulated in plasma. These results show that changes in the gut microbial community lead to alterations of the metabolic profile in blood and feces of the host and can be used to identify potentially microbiome-related metabolites. This implies that metabolomics could be a suitable tool to estimate the extent of changes induced in the intestinal microbiome with respect to consequences for the host.