Colon, a forgotten site of human xenobiotic metabolism?

Human colon contains 1.5 kg of microbiota, which actively takes part in the degradation and decomposition of the non-absorbable intake. This is common knowledge in the dietary fibre research. The concept of dietary fibre complex was proposed in 1984 including polysaccharides and ubiquitous phenolic compounds entrapped into the plant matrix. These phenolic compounds include flavonoids, phenolic acids, tannins, stilbenes and plant lignans, of which lignans are the most studied in terms of microbial metabolism in the colon. Furthermore, there is strong evidence on correlation between their intake, plasma concentration of microbial metabolites, enterodiol (END) and enterolactone (ENL), and reduced risk of chronic diseases. Colonic microbiota changes by age, diet, intestinal diseases and medication causing intra-individual variation in the metabolite pool in addition to the inter-individual variation between subjects. To address these challenges, the developed batch in vitro colon model can be coupled with an advanced metabolomics and bioinformatics platform to provide data on the circulating metabolites. This work has recently been performed for flavan-3-ol stereoisomers, (+)-catechin and (-)-epicatechin. A good correlation has been found for dietary phenolic microbial metabolites between the in vitro colon model and corresponding metabolite profiles from human body fluids. In pharmaceutical research colon has been considered only as an excretion route for non-absorbable drug remnants. Only few companies include microbial metabolism in their drug development and authorities have not given guidelines in this respect. In the case of statins, a cholesterol lowering drug, Simvastatin causes alteration in the pro-inflammatory pathways and in high doses the risk of statin induced myopathy increases. Major portion of Simvastatin is excreted via faeces and thus its adverse effects may be connected with yet unkown colonic metabolites, which identification is attempted