TY - CHAP
T1 - Colon, a forgotten site of human xenobiotic metabolism?
AU - Aura, Anna-Marja
AU - Mattila, Ismo
AU - Seppänen-Laakso, Tuulikki
AU - Oresic, Matej
AU - Oksman-Caldentey, Kirsi-Marja
PY - 2007
Y1 - 2007
N2 - 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.
AB - 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.
M3 - Conference abstract in proceedings
SN - 978-951-38-6321-0 978-951-38-6322-7
T3 - VTT Symposium
SP - 22
EP - 22
BT - Plants for Human Health in the Post-Genome Era
A2 - Kuokka-Ihalainen, Annemari
A2 - Oksman-Caldentey, Kirsi-Marja
A2 - Rischer, Heiko
A2 - Ritala, Anneli
PB - VTT Technical Research Centre of Finland
CY - Espoo
T2 - PSE Congress: Plants for Human Health in the Post-Genome Era
Y2 - 26 August 2007 through 29 August 2007
ER -