CACO-2/HT29-MTX CO-CULTURE AS AN INTESTINAL EPITHELIAL MODEL FOR INSIGHTS ON FLAVONOIDS TRANSPORT AND ABSORPTION

Cell-based models have been widely used to mimic the key features of the in vivo intestinal epithelium and investigate the bioavailability of dietary compounds. In this context, co-culture systems combining absorptive Caco-2 cells and mucus-secreting HT29-MTX cells represent a promising in vitro approach for investigating intestinal absorption and transport, providing a more physiologically relevant model.

This study evaluated the transport of the flavonoids rutin and quercetin across Caco-2 monocultures and Caco-2/HT29-MTX co-cultures established at different seeding ratios (9:1, 8:2, and 7:3). The role of the intestinal mucus layer in modulating flavonoid transport was also investigated.

The results showed that the highest transepithelial electrical resistance (TEER) values were observed in Caco-2 monocultures and Caco-2/HT29-MTX co-cultures at a 9:1 ratio. The apparent permeability of quercetin was significantly higher in comparison to rutin in both Caco-2 monoculture and Caco-2/HT29-MTX (9:1) co-culture, suggesting that the aglycone quercetin exhibits greater epithelial permeability than the glycosylated flavonoid rutin. Conversely, the presence of mucus in Caco-2/HT29-MTX (9:1) co-culture appeared to enhance rutin transport, as indicated by higher apparent permeability values compared with those observed in the Caco-2 cell monoculture.

Overall, these findings highlight the potential role of the intestinal mucus layer in modulating flavonoid transport and suggest that the presence of mucus-producing cells may differentially affect the epithelial permeability of glycosylated and aglycone forms.

Acknowledgments:

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) [Finance Code 001]

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) [grant number 25107-6, 2018]