Xenobiotics mediated modulation of gut microbiota and its role in lifestyle diseases: a critical appraisal on exposomics.

Abstract

Gastrointestinal tract of humans provides a niche to thousands of microbes, referred as gut microbiota (GM). GM establishes an intricate relationship with other organs via gut-organ axis, and modulates host health. The structure and functioning of these gut microbes can be influenced by the type of external exposome an individual experiences. Depending upon GM perturbations and host genotype, this can result in variable health implications. On the other hand, the huge arsenal of enzymes possessed by GM can chemically alter the xenobiotic structure. Its consequences can be numerous, including formation of harmful metabolites that cause organ damage, reversal of host detoxification pathways, or favourable health effects. Additionally, GM-mediated bio-transformation of pharmaceuticals can alter their pharmacokinetics and pharmacodynamics, potentially yielding variable drug responses, resulting into prolonged or ineffective treatments. To address this bi-facial relationship and the pivotal role of GM, this review incorporates recent in vitro, in vivo, and multiomics studies. It also suggests the need of machine learning approaches to decode the complex host-microbiota-xenobiotics interactions. These knowledge will aid in comprehending recent rise in chronic lifestyle-diseases which poses a huge burden on the health sector, and can also be a learning curve in making formulations and therapies for personalized treatment.