Human intestine LC-MSMS - Transcriptional and proteomic analysis revealed a synergistic effect of aflatoxin M1 and ochratoxin A mycotoxins on intestinal epithelial integrity of differentiated human Caco-2 cells

ABSTRACT: Aflatoxin M1 (AFM1) is a common mycotoxin in dairy milk and it is typically concurrently present with other mycotoxins that may represent a threat for food safety. However, knowledge on how AFM1, alone or in combination with other mycotoxins may affect human intestinal epithelial integrity remain to be established. We employed transcriptome and proteome analysis integrated with biological validation to reveal the molecular basis underlining the effect AFM1 and/or ochratoxin A (OTA) exposure on intestinal epithelial integrity of differentiated Caco-2 cells. Exposure to 4 μg/ml of OTA was found to disrupt human gut epithelial integrity, whereas 4 μg/ml of AFM1 did not. Integrated transcriptome and proteome analysis of AFM1 and OTA, alone or in combination, indicate synergistic effect of the two mycotoxins in disrupting intestinal integrity. This effect was mechanistically linked to a broad ranges of pathways related to intestinal integrity enriched by down-regulated genes and proteins, associated to focal adhesion, adherens junction, and gap junction pathways. Furthermore, the cross–omics analysis of mixed AFM1 and OTA compared with OTA alone suggest that kinases family members, including MLCK, MAPKs, and PKC are the potential key regulators on modulating intestinal epithelial integrity. These findings provide novel insight into the synergistic detrimental role of multiple mycotoxins in disrupting intestinal integrity, and, therefore, identify potential target to improve milk safety related to human health.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Epithelial Cell, Cell Culture

SUBMITTER: Yanan Gao  

LAB HEAD: Jiaqi Wang

PROVIDER: PXD009437 | Pride | 2018-08-08

REPOSITORIES: Pride