Transcriptome-based identification of the beneficial role of blackcurrant, strawberry and yellow onion to attenuate the cytopathic effects of Clostridium difficile toxins

Article type: Research Article

Authors: Venkatasubramanian, Prashanna Balaji^{a; 1} | Oosterink, Els^a | Tomassen, Monic M. M.^a | Suarez-Diez, Maria^b | Mes, Jurriaan J.^a | Saccenti, Edoardo^{b; *} | de Wit, Nicole J. W.^{a; *}

Affiliations: [a] Wageningen Food & Biobased Research, Wageningen University & Research, Wageningen, the Netherlands | [b] Laboratory of Systems and Synthetic Biology, Wageningen University & Research, Wageningen, the Netherlands

Correspondence: [*] Corresponding authors: Nicole J.W. de Wit, PhD, Wageningen Food & Biobased Research, Wageningen University & Research, P.O. Box 17, 6700 AA, Wageningen, The Netherlands, Tel.: +31 317 480310; E-mail: nicole.dewit@wur.nl and Edoardo Saccenti, PhD, Laboratory of Systems and Synthetic Biology, Wageningen University & Research, Stippeneng 4, 6708WE, Wageningen, the Netherlands. Tel.: +31 317 486948; E-mail: edoardo.saccenti@wur.nl.

Note: [1] Center for Molecular and Biomolecular Informatics, Radboud UMC, Nijmegen, the Netherlands.

Abstract: BACKGROUND:Clostridium difficile Infection (CDI) can lead to diarrhea and fulminant colitis. C. difficile infects the host using toxins. Recent studies report prevalence of CDI in the small intestine. Berries are known to contain antioxidants and phenolic compounds that might mitigate bacterial infection. OBJECTIVE:We explored the impact of C. difficile toxins on the small intestine using an in vitro approach and used systems biology techniques together with data integration to identify food compounds that can reduce their cytopathic impact. METHODS:Differentiated Caco-2 cells were exposed to C. difficile toxins and the transcriptomic changes were studied. To identify foods with potential beneficial counteracting effects, the transcriptomic profiles were integrated with transcriptomics data from Caco-2 cells exposed to various food compounds and analyzed using multivariate analysis. RESULTS:Beneficial food candidates, selected by multivariate analysis, such as blackcurrant, strawberry and yellow onion were further examined for their potential to counteract the effect of the toxin-induced disruption of cell integrity and toxin translocation. Our results confirmed effects of food compounds, on the cytopathic effects of toxins in the small intestine. CONCLUSION:Blackcurrant, strawberry and yellow onion can counteract C. difficile toxins induced effects.

Keywords: Caco-2, microarray, principal component analysis, Clostridium difficile Toxin A, Clostridium difficile Toxin B

DOI: 10.3233/JBR-200646

Journal: Journal of Berry Research, vol. 11, no. 2, pp. 231-248, 2021