PR000835 (Project)

Description:Metronidazole (15mg/kg BID PO) was given to horses (n=5) with in-dwelling cecal cannulas. The study was suspended after the fifth dose (day 3) due to adverse gastrointestinal effects. Cecal and fecal samples were obtained before and after (Days days -52, -28, -14, 0, 7, 14, 28 and 52) metronidazole administration. DNA was extracted from the cecal and fecal samples, and 16S rRNA genes were sequenced. The bacterial diversity and composition of each sample was determined. Richness and evenness indices were significantly decreased by metronidazole administration in both cecal and fecal samples, but overall composition was only significantly changed in fecal samples on Day 3 (ANOSIM, p=0.008). The most dominant phyla were Bacteroidetes and Firmicutes in all groups examined. In fecal samples, significant changes at the phyla Actinobacteria, Spirochaetes, Lentisphaerae and Verrucomicrobia occurred on Day 3, which correlated with clinical signs of gastrointestinal disease. Analysis of the predicted microbial functions using PICRUSt indicated changes associated with metronidazole in fecal samples. The metabolome was characterized by mass spectrometry-based methods. Fecal, but not cecal metabolites were affected by metronidazole. The fecal metabolites affected represented diverse metabolic pathways such as nucleic acid metabolism, secondary bile metabolism, fatty acid synthesis/degradation/elongation or metabolism and sugar metabolism.