» Articles » PMID: 23990816

Intestinal Cytochromes P450 Regulating the Intestinal Microbiota and Its Probiotic Profile

Overview
Date 2013 Aug 31
PMID 23990816
Citations 19
Authors
Affiliations
Soon will be listed here.
Abstract

Cytochromes P450 (CYPs) enzymes metabolize a large variety of xenobiotic substances. In this vein, a plethora of studies were conducted to investigate their role, as cytochromes are located in both liver and intestinal tissues. The P450 profile of the human intestine has not been fully characterized. Human intestine serves primarily as an absorptive organ for nutrients, although it has also the ability to metabolize drugs. CYPs are responsible for the majority of phase I drug metabolism reactions. CYP3A represents the major intestinal CYP (80%) followed by CYP2C9. CYP1A is expressed at high level in the duodenum, together with less abundant levels of CYP2C8-10 and CYP2D6. Cytochromes present a genetic polymorphism intra- or interindividual and intra- or interethnic. Changes in the pharmacokinetic profile of the drug are associated with increased toxicity due to reduced metabolism, altered efficacy of the drug, increased production of toxic metabolites, and adverse drug interaction. The high metabolic capacity of the intestinal flora is due to its enormous pool of enzymes, which catalyzes reactions in phase I and phase II drug metabolism. Compromised intestinal barrier conditions, when rupture of the intestinal integrity occurs, could increase passive paracellular absorption. It is clear that high microbial intestinal charge following intestinal disturbances, ageing, environment, or food-associated ailments leads to the microbial metabolism of a drug before absorption. The effect of certain bacteria having a benefic action on the intestinal ecosystem has been largely discussed during the past few years by many authors. The aim of the probiotic approach is to repair the deficiencies in the gut flora and establish a protective effect. There is a tentative multifactorial association of the CYP (P450) cytochrome role in the different diseases states, environmental toxic effects or chemical exposures and nutritional status.

Citing Articles

Microbiome as an endocrine organ and its relationship with eye diseases: Effective factors and new targeted approaches.

Haghshenas L, Banihashemi S, Malekzadegan Y, Catanzaro R, Ahmadi A, Marotta F World J Gastrointest Pathophysiol. 2024; 15(5):96446.

PMID: 39355345 PMC: 11440246. DOI: 10.4291/wjgp.v15.i5.96446.


Investigation of Intestinal Absorption and Excretion of Paracetamol in Streptozotocin-Induced Hyperglycemia.

Meszaros P, Kovacs S, Kulcsar G, Paskuj M, Almasi A Int J Mol Sci. 2022; 23(19).

PMID: 36233215 PMC: 9570177. DOI: 10.3390/ijms231911913.


Cytochrome P450 1A1 is essential for the microbial metabolite, Urolithin A-mediated protection against colitis.

Ghosh S, Moorthy B, Haribabu B, Jala V Front Immunol. 2022; 13:1004603.

PMID: 36159798 PMC: 9493474. DOI: 10.3389/fimmu.2022.1004603.


Comparative analysis of the caecal tonsil transcriptome in two chicken lines experimentally infected with Salmonella Enteritidis.

Cazals A, Rau A, Estelle J, Bruneau N, Coville J, Menanteau P PLoS One. 2022; 17(8):e0270012.

PMID: 35976909 PMC: 9384989. DOI: 10.1371/journal.pone.0270012.


Effects of Non-Polar Dietary and Endogenous Lipids on Gut Microbiota Alterations: The Role of Lipidomics.

Tsiantas K, Konteles S, Kritsi E, Sinanoglou V, Tsiaka T, Zoumpoulakis P Int J Mol Sci. 2022; 23(8).

PMID: 35456888 PMC: 9024800. DOI: 10.3390/ijms23084070.


References
1.
Thummel K, Wilkinson G . In vitro and in vivo drug interactions involving human CYP3A. Annu Rev Pharmacol Toxicol. 1998; 38:389-430. DOI: 10.1146/annurev.pharmtox.38.1.389. View

2.
Rendic S, DI CARLO F . Human cytochrome P450 enzymes: a status report summarizing their reactions, substrates, inducers, and inhibitors. Drug Metab Rev. 1997; 29(1-2):413-580. DOI: 10.3109/03602539709037591. View

3.
de Wildt S, Kearns G, Leeder J, van den Anker J . Cytochrome P450 3A: ontogeny and drug disposition. Clin Pharmacokinet. 2000; 37(6):485-505. DOI: 10.2165/00003088-199937060-00004. View

4.
Gonzalez F . The role of peroxisome proliferator activated receptor alpha in peroxisome proliferation, physiological homeostasis, and chemical carcinogenesis. Adv Exp Med Biol. 1997; 422:109-25. DOI: 10.1007/978-1-4757-2670-1_9. View

5.
Rahman A, Korzekwa K, Grogan J, Gonzalez F, Harris J . Selective biotransformation of taxol to 6 alpha-hydroxytaxol by human cytochrome P450 2C8. Cancer Res. 1994; 54(21):5543-6. View