Modulates PYY Expression in a New a Multicellular Model including Enteroendocrine Cells.

The gut microbiota contributes to human health and disease; however, the mechanisms by which commensal bacteria interact with the host are still unclear. To date, a number of in vitro systems have been designed to investigate the host-microbe interactions. In most of the intestinal models, the enteroendocrine cells, considered as a potential link between gut bacteria and several human diseases, were missing. In the present study, we have generated a new model by adding enteroendocrine cells (ECC) of L-type (NCI-H716) to the one that we have previously described including enterocytes, mucus, and M cells. After 21 days of culture with the other cells, enteroendocrine-differentiated NCI-H716 cells showed neuropods at their basolateral side and expressed their specific genes encoding proglucagon () and chromogranin A (). We showed that this model could be stimulated by commensal bacteria playing a key role in health, and , but also by a pathogenic strain such as . Moreover, using cell-free supernatants of and , we have shown that supernatant induced a significant increase in and but not in gene expression, while had no impact. Our data indicated that produced short chain fatty acids (SCFAs) such as butyrate whereas produced more propionate. However, these SCFAs were probably not the only metabolites implicated in expression since butyrate alone had no effect. In conclusion, our new quadricellular model of gut epithelium could be an effective tool to highlight potential beneficial effects of bacteria or their metabolites, in order to develop new classes of probiotics.