Gut microbiota and undigested food constituents modify toxin composition and suppress the genotoxicity of a naturally oc

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GENOTOXICITY AND CARCINOGENICITY

Gut microbiota and undigested food constituents modify toxin composition and suppress the genotoxicity of a naturally occurring mixture of Alternaria toxins in vitro Francesco Crudo1,2   · Georg Aichinger1   · Jovana Mihajlovic3 · Luca Dellafiora2   · Elisabeth Varga1   · Hannes Puntscher1 · Benedikt Warth1   · Chiara Dall’Asta2   · David Berry1,3,4   · Doris Marko1,2  Received: 15 April 2020 / Accepted: 24 June 2020 © The Author(s) 2020

Abstract Molds of the genus Alternaria produce several mycotoxins, some of which may pose a threat for health due to their genotoxicity. Due to the lack of adequate toxicological and occurrence data, they are currently not regulated. Interactions between mycotoxins, gut microbiota and food constituents might occur after food ingestion, modifying the bioavailability and, therefore, overall toxicity of mycotoxins. The present work aimed to investigate the impact of in vitro short-term fecal incubation on the in vitro DNA-damaging effects exerted by 5 µg/mL of an Alternaria alternata extract, containing, among others, 15 nM alternariol, 12 nM alternariol monomethyl ether, 241 nM altertoxin II and 301 nM stemphyltoxin III, all of which are known as genotoxic. The involvement of microorganisms, undigested food constituents and soluble substances of human fecal samples in modifying the composition and the genotoxicity of the extract was investigated through the application of LC–MS/MS analysis and comet assays in HT-29 cells. Results showed that the potential of the mycotoxins to induce DNA strand breaks was almost completely quenched, even before anaerobic incubation, by contact with the different fractions of the fecal samples, while the potency to induce formamidopyrimidine DNA glycosylase (FPG)-sensitive sites was only slightly reduced. These effects were in line with a reduction of mycotoxin concentrations found in samples analyzed by LC–MS/MS. Although a direct correlation between the metabolic activity of the gut microbiota and modifications in mycotoxin contents was not clearly observed, adsorptive phenomena to bacterial cells and to undigested food constituents might explain the observed modifications. Keywords  Mold · Microbiome · Chemical mixture · Genotoxicity · Food contaminant · Bacteria

Electronic supplementary material  The online version of this article (https​://doi.org/10.1007/s0020​4-020-02831​-1) contains supplementary material, which is available to authorized users. * Doris Marko [email protected] 1



Department of Food Chemistry and Toxicology, Faculty of Chemistry, University of Vienna, Währinger Str. 42, 1090 Vienna, Austria

2



Department of Food and Drug, University of Parma, Area Parco delle Scienze 27/A, 43124 Parma, Italy

3

Department of Microbiology and Ecosystem Science, Centre for Microbiology and Environmental Systems Science, University of Vienna, Althanstr. 14, 1090 Vienna, Austria

4

Joint Microbiome Facility of the Medical University of Vienna and the University of Vienna, Vienna, Austria





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