The gut microbiome: an orchestrator of xenobiotic metabolism

Autor: Stephanie L. Collins, Andrew D. Patterson
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Enterohepatic circulation
BDE
bromodiphenyl ether

ER
estrogen receptor

GUDCA
glycoursodeoxycholic acid

Microbial metabolism
PCB
polychlorinated biphenyl

Review
SCFA
short chain fatty acid

PD
Parkinson's disease

chemistry.chemical_compound
0302 clinical medicine
Gastrointestinal tract
NSAID
non-steroidal anti-inflammatory drug

General Pharmacology
Toxicology and Pharmaceutics

0303 health sciences
cgr
cytochrome glycoside reductase

PXR
pregnane X receptor

BRV
brivudine

CAR
constitutive androgen receptor

CV
conventional

TCDF
2
3
7
8-tetrachlorodibenzofuran

Cell biology
030220 oncology & carcinogenesis
CYP
cytochrome P450

PAH
polycyclic aromatic hydrocarbon

SULT
sulfotransferase

SN-38G
SN-38 glucuronide

Biology
BVU
bromovinyluracil

Absorption
03 medical and health sciences
FXR
farnesoid X receptor

TUDCA
tauroursodeoxycholic acid

Detoxification
Pharmacokinetics
Microbiome
Transcription factor
030304 developmental biology
Gut microbiome
Bioactivation
UGT
uracil diphosphate-glucuronosyltransferase

lcsh:RM1-950
PABA
p-aminobenzenesulphonamide

PFOS
perfluorooctanesulfonic acid

Metabolism
Xenobiotic metabolism
GF
germ-free

ALDH
aldehyde dehydrogenase

lcsh:Therapeutics. Pharmacology
chemistry
5-ASA
5-aminosalicylic acid

AHR
aryl Hydrocarbon Receptor

5-FU
5-fluorouracil

Xenobiotic
Drug metabolism
Zdroj: Acta Pharmaceutica Sinica B, Vol 10, Iss 1, Pp 19-32 (2020)
Acta Pharmaceutica Sinica. B
ISSN: 2211-3835
Popis: Microbes inhabiting the intestinal tract of humans represent a site for xenobiotic metabolism. The gut microbiome, the collection of microorganisms in the gastrointestinal tract, can alter the metabolic outcome of pharmaceuticals, environmental toxicants, and heavy metals, thereby changing their pharmacokinetics. Direct chemical modification of xenobiotics by the gut microbiome, either through the intestinal tract or re-entering the gut via enterohepatic circulation, can lead to increased metabolism or bioactivation, depending on the enzymatic activity within the microbial niche. Unique enzymes encoded within the microbiome include those that reverse the modifications imparted by host detoxification pathways. Additionally, the microbiome can limit xenobiotic absorption in the small intestine by increasing the expression of cell–cell adhesion proteins, supporting the protective mucosal layer, and/or directly sequestering chemicals. Lastly, host gene expression is regulated by the microbiome, including CYP450s, multi-drug resistance proteins, and the transcription factors that regulate them. While the microbiome affects the host and pharmacokinetics of the xenobiotic, xenobiotics can also influence the viability and metabolism of the microbiome. Our understanding of the complex interconnectedness between host, microbiome, and metabolism will advance with new modeling systems, technology development and refinement, and mechanistic studies focused on the contribution of human and microbial metabolism.
Graphical abstract Xenobiotic metabolism and gut microbiome are tightly interconnected. This review highlights major interactions between the gut microbiome, host and xenobiotic that alter xenobiotic metabolism, with a focus on therapeutic drugs. Notably, a xenobiotic's outcome is altered by the gut microbiome directly metabolizing and/or indirectly perturbing host absorption and xenobiotic metabolism.Image 1
Databáze: OpenAIRE
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