Gut microbiome-related metabolic changes in plasma of antibiotic-treated rats.
The intestinal microbiota contributes to the metabolism of its host. Adequate identification of the microbiota's impact on the host plasma metabolites is lacking. As antibiotics have a profound effect on the microbial composition and hence on the mammalian-microbiota co-metabolism, we studied the effects of antibiotics on the "functionality of the microbiome"-defined as the production of metabolites absorbed by the host. This metabolomics study presents insights into the mammalian-microbiome co-metabolism of endogenous metabolites. To identify plasma metabolites related to microbiome changes due to antibiotic treatment, we have applied broad-spectrum antibiotics belonging to the class of aminoglycosides (neomycin, gentamicin), fluoroquinolones (moxifloxacin, levofloxacin) and tetracyclines (doxycycline, tetracycline). These were administered orally for 28 days to male rats including blood sampling for metabolic profiling after 7, 14 and 28 days. Fluoroquinolones and tetracyclines can be absorbed from the gut; whereas, aminoglycosides are poorly absorbed. Hippuric acid, indole-3-acetic acid and glycerol were identified as key metabolites affected by antibiotic treatment, beside changes mainly concerning amino acids and carbohydrates. Inter alia, effects on indole-3-propionic acid were found to be unique for aminoglycosides, and on 3-indoxylsulfate for tetracyclines. For each class of antibiotics, specific metabolome patterns could be established in the MetaMap®Tox data base, which contains metabolome data for more than 550 reference compounds. The results suggest that plasma-based metabolic profiling (metabolomics) could be a suitable tool to investigate the effect of antibiotics on the functionality of the microbiome and to obtain insight into the mammalian-microbiome co-metabolism.
BASF SE, 67056, Ludwigshafen, Germany.
C
C
Behr
BASF SE, 67056, Ludwigshafen, Germany.
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H
Kamp
BASF SE, 67056, Ludwigshafen, Germany.
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E
Fabian
BASF SE, 67056, Ludwigshafen, Germany.
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G
Krennrich
BASF SE, 67056, Ludwigshafen, Germany.
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W
Mellert
Metanomics GmbH, 10589, Berlin, Germany.
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E
Peter
BASF SE, 67056, Ludwigshafen, Germany.
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V
Strauss
Metanomics GmbH, 10589, Berlin, Germany.
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T
Walk
Division of Toxicology, Wageningen University, 6700 EA, Wageningen, The Netherlands.
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IMCM
Rietjens
BASF SE, 67056, Ludwigshafen, Germany. bennard.ravenzwaay@basf.com.
B
B
van Ravenzwaay
D000617:Aminoglycosides / Q000494:pharmacology; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001769:Blood / Q000187:drug effects / Q000378:metabolism*; D001835:Body Weight / Q000187:drug effects; D004435:Eating / Q000187:drug effects; D024841:Fluoroquinolones / Q000494:pharmacology; D000069196:Gastrointestinal Microbiome / Q000187:drug effects*; D005990:Glycerol / Q000097:blood; D006626:Hippurates / Q000097:blood; D007200:Indican / Q000097:blood; D007210:Indoleacetic Acids / Q000097:blood; D055442:Metabolome / Q000187:drug effects*; D055432:Metabolomics / Q000379:methods; D017208:Rats, Wistar; D013754:Tetracyclines / Q000494:pharmacology
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D024841:Fluoroquinolones; D006626:Hippurates; D007210:Indoleacetic Acids; D013754:Tetracyclines; C030737:indoleacetic acid; D007200:Indican; D005990:Glycerol; C030514:hippuric acid
Antibiotics; Metabolomics; Microbiome; Plasma metabolite profiling; Repeated dose oral toxicity study