The effect of microbiota on metabolizing enzymes:

Studies between germ-free and conventional rats.

Rama Saad and Ramy K. Aziz

Enzyme

Function

Effect of gut microbiome

Ref.

Ethoxyresorufin-O-deethylase (EROD)

A CYP 450 dependent enzyme responsible for the biotransformation of HAAs.

The presence of normal gut flora in mice renders EROD activity higher upon ingestion of fried meat in comparison to germ free rats.

(Meinl et al, 2009)

Glutathione S-transferase A 1/2 (GSTA1/2)

Are among the alpha class of class of  GST enzymes family that are preferentially expressed in the colon rather than the liver and plays a central role in phase II detoxification of xenobiotics. In addition to that, GSTA1/2 class displays a glutathione peroxidase activity which underlies its antioxidant and cyto-protective effects.

Measuring GTSA1/2 levels in both germfree rats and microbiota re-associated rats showed 4 and 5 fold increase in the enzyme level in germfree males and females respectively with adjusting other aspects of variability as gender and tissue specific expression.

(Meinl et al, 2009)

Glutathione S-transferase A4(GSTA4)

Is 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 re-associated rats in males and females respectively.

(Meinl et al, 2009)

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 statistically significant modest elevation in colonic GSTM1 levels than rat gut microbiota associated rats. However, male rats didn't exhibit this elevation. This led the authors to suggest that the increase in germfree female rats may be underlied by a coincidence in spite of the statistical significance.

(Meinl et al, 2009)

Epoxide hydroxylase 1 (EPHX1) enzyme

Is responsible for the activation and detoxification of xenobiotics as polycyclic aromatic hydrocarbons.

Germfree rats showed substantial increase in the colon levels of EPHX1 than rats associated with rat gut microbiota.

(Meinl et al, 2009)

Epoxide hydroxylase 2 (EPHX2) enzyme

EPHX2 is located in cytosol and perixosomes and is responsible for detoxification of specific peroxides by catalyzing their conversion into dihydrodiols.

Germfree rats showed moderate increase in the colonic levels of EPHX2 than rats associated with rat gut microbiota.

(Meinl et al, 2009)

Sulfotransferase 1C2 (SULT1C2) enzyme

SULT1C2 is among the SULT1 enzyme subfamily. Which  is responsible for the conjugation of phenolic compounds with sulfo group obtained from 3'-Phosphoadenosine-5'-phosphosulfate (PAPS).

Germfree female rats showed statistically significant modest increase (1.6 fold) in colonic levels of SULT1C2.

(Meinl et al, 2009)

Sulfotransferase 1B1 (SULT1B1) enzyme

SULT1B1 is one of the SULT1 enzyme subfamily

On the contrary to SULT1C2, Germfree rats male and female rats showed statistically significant decrease (0.4 and 0.6 fold respectively) in the enzyme level than gut microbiota associated rats.

(Meinl et al, 2009)

N-acetyltransferase 1 (NAT1)

&

N-acetyltransferase 2 (NAT2)

NAT enzymes are involved in the detoxification of hydrazine and arylamine drugs.

 

NAT enzymes levels has shown modest elevation in germfree rats than rats associated with rat gut microbiota.

 

(Meinl et al, 2009)

Glutathione peroxidase 2 (GPX2) enzyme

Member of GPX family which is a selenium-dependent glutathione peroxidase that is present in the epithelium of the gastrointestinal tract.

Elevated GPX2 mRNA levels have been correlated with the association of germfree mice with microbiota.

(Meinl et al, 2009)

Refernces:

Meinl W, Sczesny S, Brigelius-Folche R, Blaut M and Glatt H. (2009). Impact of gut microbiota on   intestinal and hepatic levels of phase II xenobiotic metabolising enzymes in the rat. Drug Metabolism and Disposition. 37:1179-1186. Doi 10.1124.