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Under normal eubiotic conditions, the infiltration of gut microbes and the spread of related metabolites and toxins through the intestinal wall are carefully regulated. This regulation is achieved through the presence of a mucus layer and a tight intestinal barrier. In such a balanced state, ingested drugs are typically metabolized as expected
In a dysbiotic state, there is a disruption of tight junction complexes and intestinal epithelial cells (IECs) . As a result, gut bacteria and metabolites originating from the gut are transported to the liver through the portal vein. This process leads to inflammation and triggers alterations in the liver's metabolic functions.
Moreover, in the intestine Gut microbiota metabolizes numerous structurally diverse drugs through reactions such as reduction, hydrolysis, deamination, phosphorolysis, and decarboxylation
These modifications profoundly influence drug exposure and partially explain the significant interindividual variability in drug response
Among the gut microbiota’s newly explored roles in human biology is the ability to modify the chemical structures of foreign compounds (xenobiotics). A growing body of evidence has now provided sufficient acumen on the role of the gut microbiota on xenobiotic metabolism, which could have an intense impact on the therapy for various diseases in the future.
Gut microbial xenobiotic metabolites have altered bioavailability, bioactivity and toxicity and can intervene with the actions of human xenobiotic-metabolizing enzymes to affect the destiny of other ingested molecules.
These modifications are diverse and could lead to physiologically important consequences.
The human gut microbiota is involved in processing various xenobiotics, such as dietary compounds, industrial chemicals, and small-molecule drugs. However, there are few established connections between gut microbial enzymes and endobiotic compounds in the gastrointestinal (GI) tract.
The human gut microbiota makes an important contribution to the metabolism of ingested compounds (xenobiotics ). It converts hundreds of food components, industrial chemicals, and pharmaceuticals into metabolites with altered activities, toxicities, and lifetimes in the body. The chemistry of the xenobiotic metabolism of the gut microbes is often different from that of the host enzymes.
Despite their important consequences for human biology, the intestinal microbes, genes, and enzymes involved in xenobiotic metabolism are poorly understood.
see also:
Beta-glucuronidases
Drugs / Medications & Gut microbiota
Drugs / Medications & Metabolic activities / Metabolism
Endobiotics
Drugs / Medications & Metabolic activities / Metabolism
Pharmacobiomics
Pharmacomicrobiomics
Xenobiotics biodegradation / Drug metabolism