Fig. 4.

Multiple commensal gut bacteria convert tacrolimus to M1. (A) Representative chromatograms of bacteria incubated with tacrolimus. M1 nonproducer (Bifidobacterium longum) or producer (Clostridium aldenense, Clostridium citroniae, and Erysipelotrichaceae sp.) cultured overnight in YCFA media was incubated with tacrolimus (100 μg/ml) anaerobically at 37°C for 48 hours. The mixture was analyzed by using HPLC/UV at 210 nm. (B) Mouse or human hepatic microsomes [(HMs); 3 mg microsomal protein/ml] were incubated with tacrolimus (100 μg/ml) at 37°C for 2 hours aerobically. The mixture was analyzed by using HPLC/UV.