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The vertebrate gut microbiota have been implicated in the metabolism of xenobiotic compounds, motivating studies of microbe-driven metabolism of clinically important drugs. Here, we studied interactions between the microbiota and indomethacin, a nonsteroidal anti-inflammatory drug (NSAID) that inhibits cyclooxygenases (COX) -1 and -2. Indomethacin was tested in both acute and chronic exposure models in mice at clinically relevant doses, which suppressed production of COX-1- and COX-2-derived prostaglandins and caused small intestinal (SI) damage. Deep sequencing analysis showed that indomethacin exposure was associated with alterations in the structure of the intestinal microbiota in both dosing models. Perturbation of the intestinal microbiome by antibiotic treatment altered indomethacin pharmacokinetics and pharmacodynamics, which is probably the result of reduced bacterial β-glucuronidase activity. Humans show considerable inter-individual differences in their microbiota and their responses to indomethacin - thus, the drug-microbe interactions described here provide candidate mediators of individualized drug responses.
Pubmed ID: 26701907
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An independent, nonprofit organization focused on mammalian genetics research to advance human health. Their mission is to discover the genetic basis for preventing, treating, and curing human disease, and to enable research for the global biomedical community. Jackson Laboratory breeds and manages colonies of mice as resources for other research institutions and laboratories, along with providing software and techniques. Jackson Lab also conducts genetic research and provides educational material for various educational levels.
View all literature mentionsTHIS RESOURCE IS NO LONGER IN SERVICE. Documented on February 23,2023.Software package for comparison and analysis of microbial communities, primarily based on high-throughput amplicon sequencing data, but also supporting analysis of other types of data. QIMME analyzes and transforms raw sequencing data generated on Illumina or other platforms to publication quality graphics and statistics.
View all literature mentionsSoftware which can acquire, analyze, manage, and share mass spectrometry data. MassLynx controls any Waters mass spectrometry system, from sample and solvent management components to mass spectrometer and auxiliary detectors. The software can acquire nominal mass, exact mass, MS/MS and exact mass MS/MS data. The software system also maintains and consolidates all user sample data. Optional Application Manager programs provide additional information for specific MS analyses and data.
View all literature mentionsSource code that infers approximately-maximum-likelihood phylogenetic trees from alignments of nucleotide or protein sequences. It uses the Jukes-Cantor or generalized time-reversible (GTR) models of nucleotide evolution and the JTT, WAG, or LG models of amino acid evolution.
View all literature mentionsMus musculus with name C57BL/6J from IMSR.
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