Masked trichothecene and zearalenone mycotoxins withstand digestion and absorption in the upper GI tract but are efficiently hydrolyzed by human gut microbiota in vitro

Gratz, Silvia; Dinesh, R.; Yoshinari, Tomoya; Holtrop, Grietje; Richardson, Anthony J.; Duncan, Gary; MacDonald, Susan; Lloyd, Antony S.; Tarbin, J. A.

doi:10.1002/mnfr.201600680

Cited by 86 publications

(89 citation statements)

References 36 publications

(55 reference statements)

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“…Several in vitro studies have so far confirmed that DON3Glc is resistant to digestive juices of the upper GI tract (saliva, stomach, pancreas, bile) without any significant release of DON [25,26,27,28]. No such studies have been performed with DON3S or DON-GSH.…”

Section: Digestion and Absorption Masked Mycotoxins In The Upper Gmentioning

confidence: 99%

“…No such studies have been performed with DON3S or DON-GSH. Similarly, other important masked trichothecenes (T2αGlc, T2βGlc, HT2Glc, and NIV3Glc [13,28]) and masked zearalenone compounds (ZEN14Glc, ZEN14S, αZEL14Glc, βZEL14Glc [26,28]) have been shown in vitro to be unaffected by conditions prevailing in the upper GI tract. Masked trichothecenes (DON3Glc, NIV3Glc, T2αGlc at 2–2.3 nmol/mL) have also been shown not to be transported across intestinal epithelial monolayers (Caco-2 or Caco-2/TC7) [27,28] while their free parent compounds were transferred to various degrees (38% of DON, 6% of NIV, 42% of T2/HT2 transported after 24 h).…”

Section: Digestion and Absorption Masked Mycotoxins In The Upper Gmentioning

confidence: 99%

“…Our recent study has shown that neither ZEN14Glc nor α- and β-ZEL14Glc were transported across the intestinal epithelial monolayers with 91%–93% of a 2 µM dose being recovered from the apical cell culture medium without any significant release of free ZEN after 24 h of exposure [28]. In contrast to this, ZEN14Glc has been shown to be hydrolyzed by Caco-2 cells with 20% of a 40 µM dose of apical ZEN14Glc being released as apical ZEN after 4 h of incubation, but no hydrolysis of ZEN16Glc was reported [41].…”

Section: Digestion and Absorption Masked Mycotoxins In The Upper Gmentioning

confidence: 99%

“…Hence microbial hydrolysis of masked mycotoxins has been studied in vitro using human fecal microbiota or single isolates of human gut microbes. Several studies have demonstrated complete microbial hydrolysis of DON3Glc after 24 h of incubation [25,26,28,29]. Kinetics of hydrolysis are similar for DON3Glc and NIV3Glc, but slower for T2αGlc in mixed fecal incubations [28].…”

Section: Degradation Of Masked Mycotoxins In the Lower Gi Tractmentioning

confidence: 99%

“…Several studies have demonstrated complete microbial hydrolysis of DON3Glc after 24 h of incubation [25,26,28,29]. Kinetics of hydrolysis are similar for DON3Glc and NIV3Glc, but slower for T2αGlc in mixed fecal incubations [28]. Microbial hydrolysis rates of T2αGlc and T2βGlc were found to be similar, but T2βGlc was cleaved to T2 and HT2 while 30% of T2αGlc was converted to unknown metabolites, which could include HT2Glc, T2-triol, or T2-tetrol [13].…”

Section: Degradation Of Masked Mycotoxins In the Lower Gi Tractmentioning

confidence: 99%

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Do Plant-Bound Masked Mycotoxins Contribute to Toxicity?

Gratz

2017

Toxins

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Masked mycotoxins are plant metabolites of mycotoxins which co-contaminate common cereal crops. Since their discovery, the question has arisen if they contribute to toxicity either directly or indirectly through the release of the parent mycotoxins. Research in this field is rapidly emerging and the aim of this review is to summarize the latest knowledge on the fate of masked mycotoxins upon ingestion. Fusarium mycotoxins are the most prevalent masked mycotoxins and evidence is mounting that DON3Glc and possibly other masked trichothecenes are stable in conditions prevailing in the upper gut and are not absorbed intact. DON3Glc is also not toxic per se, but is hydrolyzed by colonic microbes and further metabolized to DOM-1 in some individuals. Masked zearalenone is rather more bio-reactive with some evidence on gastric and small intestinal hydrolysis as well as hydrolysis by intestinal epithelium and components of blood. Microbial hydrolysis of ZEN14Glc is almost instantaneous and further metabolism also occurs. Identification of zearalenone metabolites and their fate in the colon are still missing as is further clarification on whether or not masked zearalenone is hydrolyzed by mammalian cells. New masked mycotoxins continuously emerge and it is crucial that we gain detailed understanding of their individual metabolic fate in the body before we can assess synergistic effects and extrapolate the additive risk of all mycotoxins present in food.

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Section: Digestion and Absorption Masked Mycotoxins In The Upper Gmentioning

confidence: 99%

Section: Digestion and Absorption Masked Mycotoxins In The Upper Gmentioning

confidence: 99%

Section: Digestion and Absorption Masked Mycotoxins In The Upper Gmentioning

confidence: 99%

Section: Degradation Of Masked Mycotoxins In the Lower Gi Tractmentioning

confidence: 99%

Section: Degradation Of Masked Mycotoxins In the Lower Gi Tractmentioning

confidence: 99%

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Do Plant-Bound Masked Mycotoxins Contribute to Toxicity?

Gratz

2017

Toxins

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Absorption and metabolism of modified mycotoxins of alternariol, alternariol monomethyl ether, and zearalenone in Caco‐2 cells

et al. 2020

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Background and objectives Various cereals, fruits, and vegetables are commonly contaminated with mycotoxins such as zearalenone (ZEN), alternariol (AOH), and alternariol monomethyl ether (AME). More recently, their glucosidic metabolites formed in the plant have gained increasing attention. Experimental data on the contribution of modified mycotoxins to total toxicity are either controversy or lacking. Thus, the aim of this study was to investigate the absorption and metabolism of ZEN‐, AOH‐, and AME‐glucosides using the Caco‐2 cell system. Findings No quantifiable amounts of ZEN‐14‐glucoside, ZEN‐16‐glucoside, free ZEN, and ZEN metabolites were found in Caco‐2 cells and in the basolateral compartment. In contrast, glucosides of AOH and AME were absorbed and released their parental toxins, which were further metabolized to form glucuronides and sulfates to a variable extent. Metabolites were found on the basolateral site, too. There is also evidence that AOH‐9‐diglucoside is hydrolyzed to AOH‐9‐glucoside. Conclusion Our results demonstrate that modified ZEN is less absorbed whereas modified Alternaria toxins are taken up to a higher extent by Caco‐2 cells, followed by deglucosylation, metabolization, and transport to the basolateral site, suggesting a potential contribution to overall toxicity of these modified mycotoxins. Significance and novelty For the first time, absorption studies using modified Alternaria toxins in the Caco‐2 cell system were carried out.

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Species Differences in in vitro and Estimated in vivo Kinetics for Intestinal Microbiota Mediated Metabolism of Acetyl‐deoxynivalenols

Jin

Spenkelink

Beekmann

et al. 2021

Molecular Nutrition Food Res

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Scope Deoxynivalenol (DON) and its acetylated derivatives 3‐acetyl‐DON (3‐Ac‐DON) and 15‐acetyl‐DON (15‐Ac‐DON) are important mycotoxins of concern in the modern food chain. Methods and Results The present study reveals that the rate of de‐acetylation in in vitro anaerobic fecal incubations decreased in the order rat > mouse > human > pig for 3‐Ac‐DON, and mouse > human > rat > pig for 15‐Ac‐DON. The ratio between the de‐acetylation rate of 3‐Ac‐DON and 15‐Ac‐DON varies with the species. Scaling of the kinetic parameters to the in vivo situation results in catalytic efficiencies decreasing in the order human > rat > pig > mouse for 3‐Ac‐DON and human > pig > rat > mouse for 15‐Ac‐DON. The results obtained indicate that in mice, 3‐Ac‐DON can be fully deconjugated while 15‐Ac‐DON cannot. In rats, pigs, and humans, both 3‐Ac‐DON and 15‐Ac‐DON can be totally transformed by gut fecal microbiota during the estimated intestinal residence time. A correlation analysis between the deacetylation rate and the relative abundance of the microbiome suggests Lachnospiraceae may be involved in the deacetylation process. Conclusion It is concluded that interspecies differences in deacetylation of acetylated DONs exist but that in risk assessment assumption of complete intestinal deconjugation provides an adequate approach.

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Masked trichothecene and zearalenone mycotoxins withstand digestion and absorption in the upper GI tract but are efficiently hydrolyzed by human gut microbiota in vitro

Cited by 86 publications

References 36 publications

Do Plant-Bound Masked Mycotoxins Contribute to Toxicity?

Do Plant-Bound Masked Mycotoxins Contribute to Toxicity?

Absorption and metabolism of modified mycotoxins of alternariol, alternariol monomethyl ether, and zearalenone in Caco‐2 cells

Species Differences in in vitro and Estimated in vivo Kinetics for Intestinal Microbiota Mediated Metabolism of Acetyl‐deoxynivalenols

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