Manipulation of the Gut Microbiome Alters Acetaminophen Biodisposition in Mice

Journal Article · 12 March 2020 · Scientific Reports

DOI: https://doi.org/10.1038/s41598-020-60982-8 · OSTI ID:1619817

Malfatti, Michael A.; Kuhn, Edward A.; Murugesh, Deepa K.; Mendez, Melanie E.; Hum, Nicholas; Thissen, James B.; Jaing, Crystal J.; Loots, Gabriela G.

The gut microbiota is a vast and diverse microbial community that has co-evolved with its host to perform a variety of essential functions involved in the utilization of nutrients and the processing of xenobiotics. Shifts in the composition of gut microbiota can disturb the balance of organisms which can infuence the biodisposition of orally administered drugs. To determine how changes in the gut microbiome can alter drug disposition, the pharmacokinetics (PK), and biodistribution of acetaminophen were assessed in C57Bl/6 mice after treatment with the antibiotics ciprofoxacin, amoxicillin, or a cocktail of ampicillin/neomycin. Altered PK, and excretion profles of acetaminophen were observed in antibiotic exposed animals. Plasma C_max was signifcantly decreased in antibiotic treated animals suggesting decreased bioavailability. Urinary metabolite profles revealed decreases in acetaminophen-sulfate metabolite levels in both the amoxicillin and ampicillin/neomycin treated animals. The ratio between urinary and fecal excretion was also altered in antibiotic treated animals. Analysis of gut microbe composition revealed that changes in microbe content in antibiotic treated animals was associated with changes in acetaminophen biodisposition. These results suggest that exposure to amoxicillin or ampicillin/neomycin can alter the biodisposition of acetaminophen and that these alterations could be due to changes in gut microbiome composition.

• Research Organization: Lawrence Livermore National Laboratory (LLNL), Livermore, CA (United States)
• Sponsoring Organization: National Institute of General Medical Sciences (NIGMS); National Institutes of Health (NIH); USDOE Laboratory Directed Research and Development (LDRD) Program; USDOE National Nuclear Security Administration (NNSA); USDOE Office of Science (SC)
• Grant/Contract Number: AC52-07NA27344
• OSTI ID: 1619817
• Report Number(s): LLNL-JRNL--770539; 4571; PII: 60982
• Journal Information: Scientific Reports, Journal Name: Scientific Reports Journal Issue: 1 Vol. 10; ISSN 2045-2322
• Publisher: Nature Publishing GroupCopyright Statement
• Country of Publication: United Kingdom
• Language: English