Combinatory effects of cereulide and deoxynivalenol on in vitro cell viability and inflammation of human Caco-2 cells

Julia Beisl,Benedikt Warth,Chibundu N Ezekiel,Wilfred Abia,Giorgia Del Favero,Helen Abeln,Gudrun Pahlke,Monika Ehling-Schulz,Elisabeth Varga,Michael Sulyok,Doris Marko

doi:10.1007/s00204-020-02658-w

Abstract

Deoxynivalenol (DON), one of the most abundant mycotoxins in cereal products, was recently detected with other mycotoxins and the emetic bacterial toxin cereulide (CER) in maize porridge. Within a cereal-based diet, co-exposure to these toxins is likely, hence raising the question of combinatory toxicological effects. While the toxicological evaluation of DON has quite progressed, consequences of chronic, low-dose CER exposure are still insufficiently explored. Information about the combinatory toxicological effects of these toxins is lacking. In the present study, we investigated how CER (0.1–100 ng/mL) and DON (0.01–10 µg/mL) alone and in a constant ratio of 1:100 (CER:DON) affect the cytotoxicity and immune response of differentiated human intestinal Caco-2 cells. While DON alone reduced cell viability only in the highest concentration (10 µg/mL), CER caused severe cytotoxicity upon prolonged incubation (starting from 10 ng/mL after 24 h and 48 h, 2.5 ng/mL and higher after 72 h). After 72 h, synergistic effects were observed at 2.5 ng/mL CER and 0.25 µg/mL DON. Different endpoints of inflammation were investigated in interleukin-1β-stimulated Caco-2 cells. Notably, DON-induced interleukin-8 transcription and secretion were diminished by the presence of 10 and 25 ng/mL CER after short-term (5 h) incubation, indicating immunosuppressive properties. We hypothesise that habitual consumption of cereal-based foods co-contaminated with CER and DON may cause synergistic cytotoxic effects and an altered immune response in the human intestine. Therefore, further research concerning effects of co-occurring bacterial toxins and mycotoxins on the impairment of intestinal barrier integrity, intestinal inflammation and the promotion of malnutrition is needed.

Highlights

The co-occurrence of several mycotoxins and bacterial toxins was recently reported in homemade Cameroonian maize fufu, a maize porridge dish frequently consumed in West and Central Africa (Abia et al 2017)
Bacillus cereus strains with specific genotypic characteristics (Ehling-Schulz et al 2005) as well as deoxynivalenol (DON; Fig. 1b), a mycotoxin produced by Fusarium species, were detected in all analysed food samples (n = 50) (Abia et al 2017)
Toxicity of complex toxin mixtures is an emerging field of research, but combinatory effects are often considered in only one class of contaminants, for example mycotoxins (Cano-Sancho et al 2015; Vejdovszky et al 2016)

Summary

Introduction

The co-occurrence of several mycotoxins and bacterial toxins was recently reported in homemade Cameroonian maize fufu, a maize porridge dish frequently consumed in West and Central Africa (Abia et al 2017). Cereulide (CER; Fig. 1a), a bacterial toxin produced by some. Causes of childhood stunting are multifactorial and include, for example, high mycotoxin exposure, diarrhoeal diseases and intestinal inflammation (Stewart et al 2013). Insufficient nutrient absorption and growth retardation cannot be excluded to occur due to DON exposure (Smith et al 2012). Both toxins, CER and DON, cause emesis, whereas the induction of intestinal lesions (Pinton et al 2009) and alterations of the immune response (Maresca et al 2008) have been reported for DON

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Results

Conclusion