RESUMEN
Colon microbiota-based drug metabolism has received little attention thus far in the process of drug development, whereas the role of gut microbiota in clinical safety and efficacy of drugs has become more clear. Many of these studies have been performed using animal studies, but the translational value of these data with respect to drug pharmacokinetics, efficacy, and safety is largely unknown. To investigate human colon microbiota-mediated drug metabolism, we applied a recently developed ex vivo fermentation screening platform, in which human colonic microbiota conditions are simulated. A set of 12 drugs (omeprazole, simvastatin, metronidazole, risperidone, sulfinpyrazone, sulindac, levodopa, dapsone, nizatidine, sulfasalazine, zonisamide, and acetaminophen) was incubated with human colon microbiota under strictly anaerobic conditions, and samples were analyzed using high-performance liquid chromatograph-UV-high-resolution mass spectrometry analysis. The human microbiota in the fermentation assay consisted of bacterial genera regularly encountered in human colon and fecal samples and could be reproducibly cultured in independent experiments over time. In addition, fully anaerobic culture conditions could be maintained for 24 hours of incubation. Five out of the 12 included drugs (sulfasalazine, sulfinpyrazone, sulindac, nizatidine, and risperidone) showed microbiota-based biotransformation after 24 hours of incubation in the ex vivo fermentation assay. We demonstrated that drug metabolites formed by microbial metabolism can be detected in a qualitative manner and that the data are in accordance with those reported earlier for in vivo metabolism. In conclusion, we present a research tool to investigate human colon microbiota-based drug metabolism that may be applied to enable translatability of microbiota-based drug metabolism.
Asunto(s)
Fermentación/fisiología , Microbioma Gastrointestinal/fisiología , Inactivación Metabólica/fisiología , Preparaciones Farmacéuticas/metabolismo , Adulto , Colon/metabolismo , Colon/microbiología , Heces/microbiología , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Contamination with SE is an important threat to food safety in egg production. Various risk factors exist for infection with and spreading of SE on a farm. A data set of regularly collected blood samples from hens at the end of lay was available for analysis. Data included information about infection with SE, date of sampling, housing system and flock size and whether there were hens of different ages on the farm or in the house. By using the mentioned data set, our objective was to identify risk factors associated with SE infection in laying hens. Multiple logistic regression was used to assess the contribution of different variables. Results showed that bigger flocks increased the chance of infection with SE in all housing systems. The system with the lowest chance of infection was the cage system with wet manure. An outdoor run increased the chance of infection only at farms with all hens of the same age. The presence of hens of different ages on a farm was a risk factor for deep litter systems only. This resulted in the highest chance of infection for a deep litter system on a farm with hens of different ages. On a farm with all hens of the same age, however, a deep litter system did not increase the chance of infection with SE compared with a cage system. The main risk factors associated with SE infection, therefore, were flock size, housing system, and farm with hens of different ages.