Host: Paul Kroon

Abstract:

Dietary plant polyphenols such as lignans and flavonoids have been implicated in the prevention of cardiovascular disease, cancer, obesity and other chronic diseases. Gut bacteria are capable of converting various polyphenols into metabolites that exert biological activity in the host. Daidzein and genistein and their glycosides are the most common isoflavones present in soy and they may therefore be consumed in considerable amounts. They have been implicated in the prevention of hormone-related cancers and cardiovascular disease. In the case of the model compound daidzein, these effects have mainly been attributed to one of its bacterial transformation products, namely equol. We isolated the human gut bacterium Slackia isoflavoniconvertens which is capable of converting daidzein to the biologically active equol and characterized the steps involved in this conversion. Furthermore we are interested in the conversion of C-glycosidic isoflavones such as puerarin.

Various diseases, including obesity and chronic inflammatory bowel diseases are associated with microbiota patterns that deviate from those of healthy subjects. Whether these links are causal and which molecular mechanisms are involved is largely unknown. Abundance of the gut bacterium Clostridium ramosum in human cohorts has been linked to obesity. Moreover, C. ramosum was shown to enhance obesity development in gnotobiotic mice fed high fat diet. This was accompanied by increased expression of genes involved in small intestinal fat uptake. Metabolomic analysis revealed that mice associated with C. ramosum displayed higher levels of plasma serotonin (5-hydroxytryptamine; 5-HT) compared with mice devoid of this organism. In the intestine, 5-HT is synthesised by enterochromaffin cells (ECs). Peripheral 5-HT plays an important role in obesity by regulating lipid and glucose metabolism whereas central serotonin has anorexigenic function. Recent studies showed that indigenous gut microbiota can modulate 5-HT signalling and ECs use sensory receptors to detect dietary and microbiota-derived signals from the lumen and to transduce information to the nervous system. We hypothesized that C. ramosum promote obesity by stimulating 5-HT synthesis. Using germfree mice and mice monoassociated with C. ramosum we demonstrated that C. ramosum stimulates host serotonin production by programming the differentiation of intestinal stem cells toward the secretory serotonin-producing ECs. These in vivo results were confirmed using rat RIN14B cells and human HT-29 cells. It may be concluded that elevated 5-HT levels increase the expression of major proteins involved in fatty acid translocation in intestinal and adipose tissue and subsequent fat accumulation. This supports the notion that C. ramosum promotes obesity by enhancing nutrient absorption.

All staff from organisations on the Research Park are welcome to attend.