Figure 2.

Examples of facilitation or interruption of gut microbial metabolism for drug therapy or other therapeutic approaches. a. The metabolism of irinotecan in the body and the transformation of its anticancer activity. Specially, it can be metabolized by the host carboxylesterases to its active form, SN38, which is then de-activated into SN38G by host UDP-glucuronosyltransferases. The SN38G can enter the intestine and be converted into SN38 by β-glucuronidases of gut microbe. b. The activation of the capecitabine by gut microbes. The capecitabine can be metabolized into its active form, the 5-fluoro-5’-deoxyuridine (5’DFUR), by thymidine phosphorylase (TP) of gut microbes. c. The activation of the thioguanine by gut microbes. The thiopurine was administrated local to the gut and activated into functionally thioguanine nucleotides. d,e. De-active metabolism of drugs by gut microbes. Four anticancer drugs, gemcitabine, doxorubicin, 5-fluoro-2’-deoxyuridine (FdUrd), and 5-trifluorothymidine (TFT), can be degraded by gut microbes to their inactive forms. f. The bacterial toxicity-enhancing effects of some toxic substances. Gut microbes can convert the FUdR to the toxic 5-fluorouridine-5’-monophosphate (FUMP). g. Adjunctive effect of gut microbial inosine on immune checkpoint blockade (ICB). Inosine produced by Bifidobacterium pseudolongum (B. pseudolongum) can promote the derivation and activation of Th1 cells and enhance the therapeutic effect of ICB.