User:Mmahmed1/Gut microbiota

Gut Microbiota Contribution to Drug Metabolism
The gut microbiota is an enriched community that contains diverse genes with huge biochemical capabilities to modify drugs, especially those taken by mouth.[1] Gut microbiota can affect drug metabolism via direct and indirect mechanisms. The direct mechanism is mediated by the microbial metabolites that can modify the chemical structure of the administered drugs. Conversely, the indirect pathway is mediated by the microbial metabolites which affect the expression of host metabolizing enzymes such as Cytochrome P450s. The effects of the gut microbiota on the pharmacokinetics and bioavailability of the drug have been investigated for a very long time ago. These effects can be varied; it could activate the inactive drugs such as lovastatin, inactivate the active drug such as digoxin or induce drug toxicity as in irinotecan.

The human gut microbiota plays a crucial role in modulating the effect of the administered drugs on the human. Directly, gut microbiota can synthesize and release a series of enzymes with the capability to metabolize drugs such as the chemical biotransformation of L-dopa by decarboxylase and dehydroxylase enzymes. On the contrary, gut microbiota may also alter the metabolism of the drugs by modulating the host drug metabolism. This mechanism can be mediated by microbial metabolites or by modifying hot metabolites.

A large number of studies have demonstrated the metabolism of over 50 drugs by the gut microbiota. For example, lovastatin (a cholesterol-lowering agent) which is a lactone prodrug is partially activated by the human gut microbiota forming active acid hydroxylated metabolites. Conversely, digoxin (a drug used to treat Congestive Heart Failure) is inactivated by a member of the gut microbiota (i.e. Eggerthella lanta).[2] Eggerthella lanta has a cytochrome-encoding operon up-regulated by digoxin and associated with digoxin-inactivation. Gut microbiota can also modulate the efficacy and toxicity of chemotherapeutic agents such as irinotecan. This effect is derived from the microbiome-encoded β-glucuronidase enzymes which recover the active form of the irinotecan causing gastrointestinal toxicity.

1- Absorption and Distribution.
Drug absorption is a process of moving the drug from the site of administration to the systemic circulation, while the distribution of the drug is the transfer to the target site of action. Probiotic Escherichia coli strain Nissle (EcN)

2- Metabolism and Excretion
Drug metabolism is a process of modification of the drug into a more polar form to facilitate its elimination from the body. This process is critical in the detoxification of the drug which is mainly mediated via Cytochrome P450 enzymes. Drug excretion includes exporting drugs outside the body with urine or other pathways.

Bioavailability and Toxicity
Gut microbiota also play roles in drug bioavailability and toxicity by activating, inactivating, and inducing toxicities (I don't understand this phrase "inducing toxicities")

Examples and figure
Amiodarone

Levodopa

Irinotecan

Digoxin

Lovastatin

Gut Microbiome Metabolites
Gut microbiota is a diverse microbial community composed of more than 100 trillion cells and approximately 5 million genes outnumbering human cells and genes. This community has a huge biochemical capability to produce distinct secondary metabolites that are sometimes produced from the metabolic conversion of dietary foods such as fibers or endogenous biological compounds such as Indoles. Secondary metabolites produced by gut microbiota play crucial roles for the human host, for example, Short Chain Fatty Acids (SCFAs) such as butyrate can support the innate immune system.