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Gene expression profiles of Caco-2 cells treated with cholic acid

ABSTRACT: Colorectal cancer (CRC) is the third most common cancer in men and the second in women worldwide, with most of the case occurrences in developed regions. CRC can be induced by luminal factors, like dietary components and bile acids. Bile acids are metabolized from cholesterol in the liver, stored in the gallbladder and released into the small intestine upon meal ingestion to facilitate the absorption of dietary lipids and lipid-soluble vitamins. Bile acids are effectively reabsorbed at the distal ileum and returned to the liver, and only a small portion (~2-5%) enters the colon. Here primary bile acids, like cholic acid (CA) and chenodeoxycholic acid (CDCA) are deconjugated by bacteria and secondary bile acids are formed, such as deoxycholic acid (DCA), ursodeoxycholic acid (UDCA) and lithocholic acid. DCA is the major component of the colonic bile acid pool and is found to be increased upon a high fat diet. Moreover, high levels of DCA are known to increase the risk of colorectal cancer by inducing cytotoxicity to epithelial cells. In this study the cytotoxicity of Caco-2 cells to stimulation with cholic acid is investigated.

ORGANISM(S): Homo sapiens

PROVIDER: GSE120699 | GEO | 2021/10/01

REPOSITORIES: GEO

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Project description:In order to successfully survive in and to colonize the gastrointestinal tract, bacteria need to develop strategies to overcome bile acid stress. The most prominent bile acids are the primary bile acids cholic acid (CA) and chenodeoxycholic acid (CDCA) as well as the secondary bile acid deoxycholic acid (DCA). In this study, we investigated the stress response of E. faecalis and E. faecium to sublethal concentrations of these three bile acids on the proteome level using DIA-MS. As both species showed similar IC50 for DCA and CDCA in growth experiments and both were highly resistant towards CA, we assumed similar changes to their protein expression profiles. Moreover, we investigated proteomic differences of E. faecalis grown under aerobic or microaerophilic conditions. Our findings showed similarities, but also species-specific variations in the response to the different bile acids, which reveal potential differences in the adaptation process. DCA and CDCA had a strong effect on down-expression of proteins involved in translation, transcription and replication in E. faecalis, but to a lesser extent in E. faecium. Proteins commonly significantly altered in their expression in all bile acid treated samples were identified for both species and represent a “general bile acid response”. Among these, ABC-transporters, multi-drug transporters and proteins related to cell wall biogenesis were up-expressed in both species and thus seem to play an essential role in bile acid resistance. Specific for all E. faecalis samples was the up-expression of several subunits of a V-type ATPase and the down-expression of proteins involved in pyruvate-, citrate- and folate metabolism. Most of the differentially expressed proteins were also identified when E. faecalis was incubated with low levels of DCA at microaerophilic conditions in comparison to aerobic conditions, indicating that adaptations to bile acids and to a microaerophilic atmosphere can occur simultaneously.

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Gene expression profiles of Caco-2 cells treated with cholic acid

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