title: Effects of Digested Onion Extracts on Intestinal Gene Expression: An Interspecies Comparison Using Different Intestine Models.
abstract: Human intestinal tissue samples are barely accessible to study potential health benefits of nutritional compounds. Numbers of animals used in animal trials, however, need to be minimalized. Therefore, we explored the applicability of in vitro (human Caco-2 cells) and ex vivo intestine models (rat precision cut intestine slices and the pig in-situ small intestinal segment perfusion (SISP) technique) to study the effect of food compounds. In vitro digested yellow (YOd) and white onion extracts (WOd) were used as model food compounds and transcriptomics was applied to obtain more insight into which extent mode of actions depend on the model. The three intestine models shared 9,140 genes which were used to compare the responses to digested onions between the models. Unsupervised clustering analysis showed that genes up- or down-regulated by WOd in human Caco-2 cells and rat intestine slices were similarly regulated by YOd, indicating comparable modes of action for the two onion species. Highly variable responses to onion were found in the pig SISP model. By focussing only on genes with significant differential expression, in combination with a fold change > 1.5, 15 genes showed similar onion-induced expression in human Caco-2 cells and rat intestine slices and 2 overlapping genes were found between the human Caco-2 and pig SISP model. Pathway analyses revealed that mainly processes related to oxidative stress, and especially the Keap1-Nrf2 pathway, were affected by onions in all three models. Our data fit with previous in vivo studies showing that the beneficial effects of onions are mostly linked to their antioxidant properties. Taken together, our data indicate that each of the in vitro and ex vivo intestine models used in this study, taking into account their limitations, can be used to determine modes of action of nutritional compounds and can thereby reduce the number of animals used in conventional nutritional intervention studies.
authors.affiliation: Food & Biobased Research, Wageningen University and Research Centre, Wageningen, The Netherlands.
authors.forename: Nicole J W
authors.initials: NJ
authors.lastname: de Wit
authors.affiliation: Wageningen Livestock Research, Wageningen University and Research Centre, Wageningen, The Netherlands.
authors.forename: Marcel
authors.initials: M
authors.lastname: Hulst
authors.affiliation: Food & Biobased Research, Wageningen University and Research Centre, Wageningen, The Netherlands.
authors.forename: Coen
authors.initials: C
authors.lastname: Govers
authors.affiliation: Wageningen Livestock Research, Wageningen University and Research Centre, Wageningen, The Netherlands.
authors.forename: Jan
authors.initials: J
authors.lastname: van der Meulen
authors.affiliation: RIKILT-Institute of Food Safety Wageningen University and Research Centre, Wageningen, The Netherlands.
authors.forename: Angeline
authors.initials: A
authors.lastname: van Hoef
authors.affiliation: RIKILT-Institute of Food Safety Wageningen University and Research Centre, Wageningen, The Netherlands.
authors.forename: Geert
authors.initials: G
authors.lastname: Stoopen
authors.affiliation: RIKILT-Institute of Food Safety Wageningen University and Research Centre, Wageningen, The Netherlands.
authors.forename: Astrid
authors.initials: A
authors.lastname: Hamers
authors.affiliation: Wageningen Livestock Research, Wageningen University and Research Centre, Wageningen, The Netherlands.
authors.forename: Arjan
authors.initials: A
authors.lastname: Hoekman
authors.affiliation: Plant Research International, Wageningen University and Research Centre, Wageningen, The Netherlands.
authors.forename: Ric
authors.initials: R
authors.lastname: de Vos
authors.affiliation: RIKILT-Institute of Food Safety Wageningen University and Research Centre, Wageningen, The Netherlands.
authors.forename: Toine F H
authors.initials: TF
authors.lastname: Bovee
authors.affiliation: Wageningen Livestock Research, Wageningen University and Research Centre, Wageningen, The Netherlands.
authors.forename: Mari
authors.initials: M
authors.lastname: Smits
authors.affiliation: Food & Biobased Research, Wageningen University and Research Centre, Wageningen, The Netherlands.
authors.forename: Jurriaan J
authors.initials: JJ
authors.lastname: Mes
authors.affiliation: RIKILT-Institute of Food Safety Wageningen University and Research Centre, Wageningen, The Netherlands.
authors.forename: Peter J M
authors.identifier: http://orcid.org/0000-0002-0951-3270
authors.initials: PJ
authors.lastname: Hendriksen
mesh_terms: D000818:Animals; D018938:Caco-2 Cells; D015870:Gene Expression / Q000187:drug effects*; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000187:drug effects*; D019697:Onions / Q000737:chemistry*; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D013045:Species Specificity
chemical_list: D010936:Plant Extracts