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Abstract
Humans are exposed to numerous xenobiotics, a majority of which are in the form of pharmaceuticals. Apart from human enzymes, recent studies have indicated the role of the gut bacterial community (microbiome) in metabolizing xenobiotics. However, little is known about the contribution of the plethora of gut microbiome in xenobiotic metabolism. The present study reports the results of analyses on xenobiotic metabolizing enzymes in various human gut microbiomes. A total of 397 available gut metagenomes from individuals of varying age groups from 8 nationalities were analyzed. Based on the diversities and abundances of the xenobiotic metabolizing enzymes, various bacterial taxa were classified into three groups, namely, least versatile, intermediately versatile and highly versatile xenobiotic metabolizers. Most interestingly, specific relationships were observed between the overall drug consumption profile and the abundance and diversity of the xenobiotic metabolizing repertoire in various geographies. The obtained differential abundance patterns of xenobiotic metabolizing enzymes and bacterial genera harboring them, suggest their links to pharmacokinetic variations among individuals. Additional analyses of a few well studied classes of drug modifying enzymes (DMEs) also indicate geographic as well as age specific trends.
Highlights
Advancements in medicine as well as health care, along with increasing awareness of health and hygiene have resulted in a significant rise in the demand and consumption of pharmaceuticals [1]
Based on the diversity of the enzymes harboured, the members belonging to G1, G2 and G3 could be classified as least versatile (LV), intermediately versatile (IV) and highly versatile (HV) xenobiotic metabolizers, respectively
Since the majority of drugs are structurally homologous to some xenobiotic or intermediates of the corresponding metabolizing pathway, they are likely to be metabolized by enzymes of the same degrading pathways
Summary
Advancements in medicine as well as health care, along with increasing awareness of health and hygiene have resulted in a significant rise in the demand and consumption of pharmaceuticals [1]. Reports have indicated that for certain countries ( in the middle income group), the consumption of drugs (especially those belonging to the Sulphonyl urea based categories) in the last decade has gone up by more than 250% (http://www.who.int/medicines/ areas/policy/world_medicines_situation/en/index.html). Humans are increasingly exposed to various xenobiotics, which are typically the precursors of almost all categories of drugs/pharmaceuticals. Given the foreign nature of these compounds (with respect to the human physiology), their metabolism, elimination and toxicity have become a major concern for clinicians and researchers working in areas of health sciences. Drugs administered orally pass through the alimentary canal and subsequently undergo a series of modifications.
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