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Table 2 Effect of microbiota on hepatic and intestinal metabolic enzymes [28]

From: Gut Pharmacomicrobiomics: the tip of an iceberg of complex interactions between drugs and gut-associated microbes

Enzyme Function Effect of gut microbiome
Ethoxyresorufin-O-deethylase (EROD) A CYP450-dependent enzyme responsible for the biotransformation of HAAs The presence of normal gut microbiota in rats potentiates EROD activity upon ingestion of fried meat
Glutathione S-transferase A 1/2 (GSTA1/2) Being among the alpha class of GST enzyme family that is preferentially expressed in the colon rather than the liver, it plays a central role in phase II detoxification of xenobiotics. In addition, GSTA1/2 class displays a glutathione peroxidase activity, which underlies its antioxidant and cyto-protective effects. Measuring GSTA1/2 levels in both germfree rats and microbiota–reassociated rats showed 4- and 5-fold increase in the enzyme level in germfree males and females, respectively.
Glutathione S-transferase A4(GSTA4) Among the alpha class of GST enzymes that possess high affinity to alk-2-enes Germfree rats showed 1.5- and 1.9-fold increase in the levels of GSTA4 than microbiota–reassociated rats in males and females, respectively.
Glutathione S-transferase M1 (GSTM1) GSTM1 is one of the mu class of GSTs which detoxify carcinogens, toxins, drugs and oxidative stress products. Germfree female rats showed a statistically significant but modest elevation in colonic GSTM1 levels compared to rats with gut microbiota. However, male rats didn't exhibit this elevation. This increase in germfree female rats may be coincidental in spite of the statistical significance.
Epoxide hydroxylase 1 (EPHX1) enzyme Responsible for the activation and detoxification of xenobiotics as polycyclic aromatic hydrocarbons Germfree rats showed a substantial increase in the colonic levels of EPHX1 than rats associated with rat gut microbiota.
Epoxide hydroxylase 2 (EPHX2) enzyme Located in cell cytosol and perixosomes and detoxifies specific peroxides by catalyzing their conversion into dihydrodiols Germfree rats showed a moderate increase in the colonic levels of EPHX2 than rats associated with rat gut microbiota.
Sulfotransferase 1C2 (SULT1C2) enzyme Among the SULT1 enzyme subfamily, which conjugates phenolic compounds with sulfo groups obtained from 3'-Phosphoadenosine-5'-phosphosulfate (PAPS) Germfree female rats showed a statistically significant modest increase (1.6-fold) in colonic levels of SULT1C2.
Sulfotransferase 1B1 (SULT1B1) enzyme A member of the SULT1 enzyme subfamily On the contrary to SULT1C2, germfree male and female rats showed a statistically significant decrease (0.4- and 0.6-fold, respectively) in the enzyme level than gut microbiota- associated rats.
N-acetyltransferase 1 (NAT1) & N-acetyltransferase 2 (NAT2) enzyme Detoxify hydrazine and arylamine drugs NAT enzyme levels were modestly elevated in germfree rats in comparison with rats with conventional gut microbiota.
Glutathione peroxidase 2 (GPX2) enzyme A selenium-dependent member of the GPX family of glutathione peroxidase that is present in the epithelium of the gastrointestinal tract Elevated GPX2 mRNA levels have been correlated with the reintroduction of microbiota in germfree rats.