Deoxynivalenol increases pro-inflammatory cytokine secretion and reduces primary bile acid transport in an inflamed intestinal in vitro co-culture model

• Published in: Food research international 2023-11, Vol.173, p.113323-113323, Article 113323
• Main Authors: Wang, Jingxuan, Bakker, Wouter, de Haan, Laura, Bouwmeester, Hans
• Format: Article
• Language: English
• Subjects: absorption; bile; Bile acid transport; chenodeoxycholic acid; coculture; cytokines; Deoxynivalenol; epithelium; food research; fungi; grain foods; humans; In vitro co-cultures; Inflammation; Intestine; intestines; macrophages; malabsorption; Primary bile acid; secondary metabolites; secretion
• ISSN: 0963-9969; 1873-7145
• DOI: 10.1016/j.foodres.2023.113323

[Display omitted] •A novel intestinal in vitro co-culture model was developed to study the active transport in the inflamed intestine.•The active transport of primary bile acids is reduced in the inflamed co-cultures compared to healthy co-cultures.•Deoxynivalenol increases pro-inflammatory cytokine secretion and reduces bile acid transport in an inflamed intestine.•Local activation of immune cells reinforces the direct pro-inflammatory effects of DON on epithelial cells in intestine. The fungal secondary metabolite deoxynivalenol (DON) that can contaminate cereal-based food products not only induces inflammation but also reduces bile acid absorption by a healthy human intestine. Bile acid malabsorption is commonly observed in individuals with an inflamed intestine. Here we studied the effects of DON on inflammation and primary bile acid transport using an in vitro model for an inflamed intestine. An inflamed intestinal in vitro model was established by co-culturing a Caco-2 cell-layer and LPS-pre-stimulated THP-1 macrophages in Transwells. We observed a decreased transport of 5 primary bile acids across inflamed co-cultures compared to healthy co-cultures but not of chenodeoxycholic acid. DON exposure further reduced the transport of the affected primary bile acids across the inflamed co-cultures. DON exposure also enhanced the secretion of pro-inflammatory cytokines in the inflamed co-cultures, while it did not increase the pro-inflammatory cytokines secretion from LPS-pre-stimulated THP-1 monocultures. Exposure of Caco-2 cell-layers to pro-inflammatory cytokines or THP-1 conditioned media partly mimicked the DON-induced effects of the co-culture model. Local activation of intestinal immune cells reinforces the direct pro-inflammatory effects of DON on intestinal epithelial cells. This affects the bile acid intestinal kinetics in an inflamed intestine.