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Abstract
The evolution of the complex metabolic interaction between intestinal microbiota in the human gut with its host is multidimensional. Our understanding of this complex interaction has evolved in the past years either with the use of more sophisticated analytical techniques or by reported adverse drug effects that have been associated with intestinal drug metabolism such as with sorivudine. The composition of the intestinal microbiome is initially determined by environmental and genetic factors although external influences as well as host immune reactions provide for adjustment of the delicate balance in both health and disease conditions. The metabolism of drugs by both intestinal bacteria and further by enterocytes leading to their systemic absorption deserves further attention and may provide valuable insights into pre-systemic drug metabolism, delivery, and toxicity. A better understanding of the metabolic pathways may aid in the drug development and toxicity evaluation process.
Highlights
The evolution of our understanding of the processes involved in drug metabolism has considerably influenced the field of drug discovery and toxicity over the past three decades
Dose-dependent absorption and metabolism occur through transporters and enzyme saturation that may lead to adverse effects and toxicity as well as increased or decreased serum concentrations of the active drug [3]
Genetic differences such as enzyme polymorphisms, disease states, and metabolic activity differ widely among individuals [4]. All of these variables are well known to contribute to drug metabolism and effect and have been considered for decades even for models that only involve the liver and the blood-soluble enzymes as places of metabolic activity
Summary
The evolution of our understanding of the processes involved in drug metabolism has considerably influenced the field of drug discovery and toxicity over the past three decades. Such symbiotic interactions develop shortly after birth and remain fairly constant in the healthy population whereas acute disease states or loss of bacterial equilibrium following antibiotic therapy may account for the development of chronic disorders that can permanently affect the ability of the host to process food optimally [25,26] It appears that both the host genotype and the metabolic phenotype are at least in part influenced by the composition of the intestinal microbiome and the host genotype influences the colonization of the intestines by microbes [7,16,23]. A better understanding of the interplay between microbial and enterocyte metabolism is important for drug design, development, and clinical outcome of drug treatment
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