Figure 3.

Interactions of gut microbiota with therapeutic drugs.

The black dotted arrow represented the absorption process of drugs. The bold grey arrow represented a schematic interaction of the gut microbiota with the immune-metabolic axis and the different mechanisms proposed to explain its implication in toxicity efficacy and health/disease risk. Mechanisms underlying the connection of drugs-induced host detoxifying metabolism activation influenced by gut microbiota (e.g. multidrug resistance protein, MDRs; the cytochrome P450 superfamily, CYPs; and the ATP-binding cassett transporters, ABC transporters) and microbiota biotransformations (e.g. hydrolysis, dehydroxylation, denitration, amine formation and proteolysis). Drugs metabolism occurs associated to the energetic cell metabolism; and the endocannabinoid system (eCB) participates in the regulation of energy homeostasis and gut permeability (increasing the possibility to appears a metabolic endotoxemia). The deregulation of cellular energetic metabolism could impair the activation of ABC transporters causing together inflammation (cytokines production) and alterations in gut permeability increasing the toxic effects.