Gut microbiota-mediated metabolism

Gut microbiota-mediated metabolism refers to the collective biochemical transformations performed by the trillions of microorganisms residing in the human gastrointestinal tract [Nicholson et al., 2012]. This metabolic system possesses a genetic diversity that vastly exceeds that of the human host, allowing it to perform unique chemical reactions such as anaerobic reductions and hydrolyses [Spanogiannopoulos et al., 2016]. These processes are critical for the breakdown of complex dietary polysaccharides into short-chain fatty acids (SCFAs), which regulate host energy balance and immune function [Koh et al., 2016]. In the context of pharmacology, microbial enzymes can significantly alter drug efficacy and safety; for example, bacterial beta-glucuronidases can reactivate the chemotherapy drug irinotecan in the gut, leading to severe intestinal toxicity [Wallace et al., 2010]. Additionally, the microbial conversion of dietary nutrients like choline into trimethylamine (TMA) is a key step in the production of the pro-atherogenic metabolite TMAO, linking the microbiota to cardiovascular disease [Wang et al., 2011]. Because the composition of the microbiota varies significantly between individuals, this metabolic axis is a major driver of inter-individual variability in drug response and disease susceptibility [Koppel et al., 2017]. Therapeutic strategies targeting this system include the use of prebiotics, probiotics, and small-molecule inhibitors of specific microbial enzymes to improve drug outcomes and host health [Zimmermann et al., 2019].

Other names

Gut microbial metabolismIntestinal microbial biotransformationXenobiotic metabolism by gut microbiotaMicrobiome-mediated drug metabolism

Microbial enzymes (e.g., azoreductases, beta-glucuronidases, and decarboxylases) chemically modify drugs through reduction, hydrolysis, or deconjugation, which can activate prodrugs, inactivate active compounds, or generate toxic metabolites [Spanogiannopoulos et al., 2016].