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

Silvia W. Gratz, Reshma Dinesh, Tomoya Yoshinari, Grietje Holtrop, Anthony J. Richardson, Gary Duncan, Susan MacDonald, Antony Lloyd, Jonathan Farbin

Research output: Contribution to journalArticle

19 Citations (Scopus)
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Abstract

Scope

Cereal grains are commonly contaminated with Fusarium mycotoxins and their plant-derived masked metabolites. The fate of masked mycotoxins in the human gut is poorly understood. Here we assess the metabolism and transport of glucoside metabolites of common trichothecenes (deoxynivalenol, nivalenol, T-2 toxin) and zearalenone compounds (zearalenone, α- and β-zearalenol) in the human gut in vitro.
Methods and Results

Masked mycotoxins were incubated with artificial digestive juices and absorption was assessed in differentiated Caco-2/TC7 cells. Colonic metabolism was studied using fecal batch cultures from 5 donors and mycotoxins were detected using LC-MS/MS. All masked mycotoxins were stable under upper GI tract conditions and no absorption was observed. Free trichothecenes were absorbed intact whereas free zearalenone compounds were absorbed and metabolized to undetected compounds by Caco-2/TC7 cells. Human gut microbiota efficiently hydrolyzed all masked mycotoxins. Trichothecenes were fully recovered as parent mycotoxins whereas 40–70% of zearalenone compounds were further metabolized to unknown metabolites.
Conclusion

Our results demonstrate that masked trichothecenes will reach the colon intact to be released as parent mycotoxins by gut microbiota, hence contributing to mycotoxin exposure. Masked zearalenone compounds are metabolized by gut microbiota and epithelial cells and the identity and toxicity of metabolites remain to be determined.
Original languageEnglish
Article number1600680
JournalMolecular Nutrition & Food Research
Volume61
Issue number4
Early online date6 Feb 2017
DOIs
Publication statusPublished - Apr 2017

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Trichothecenes
Zearalenone
Upper Gastrointestinal Tract
trichothecenes
Mycotoxins
zearalenone
intestinal microorganisms
mycotoxins
gastrointestinal system
Digestion
digestion
metabolites
Caco-2 Cells
digestive system
digestive juices
zearalenol
T-2 Toxin
Gastrointestinal Microbiome
In Vitro Techniques
nivalenol

Keywords

  • Caco-2
  • deoxynivalenol
  • glucoside
  • hydrolysis
  • nivalenol
  • HT-2 toxin

Cite this

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 W.; Dinesh, Reshma; Yoshinari, Tomoya; Holtrop, Grietje; Richardson, Anthony J.; Duncan, Gary; MacDonald, Susan ; Lloyd, Antony ; Farbin, Jonathan.

In: Molecular Nutrition & Food Research, Vol. 61, No. 4, 1600680, 04.2017.

Research output: Contribution to journalArticle

Gratz, Silvia W. ; Dinesh, Reshma ; Yoshinari, Tomoya ; Holtrop, Grietje ; Richardson, Anthony J. ; Duncan, Gary ; MacDonald, Susan ; Lloyd, Antony ; Farbin, Jonathan. / Masked trichothecene and zearalenone mycotoxins withstand digestion and absorption in the upper GI tract but are efficiently hydrolyzed by human gut microbiota in vitro. In: Molecular Nutrition & Food Research. 2017 ; Vol. 61, No. 4.
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title = "Masked trichothecene and zearalenone mycotoxins withstand digestion and absorption in the upper GI tract but are efficiently hydrolyzed by human gut microbiota in vitro",
abstract = "ScopeCereal grains are commonly contaminated with Fusarium mycotoxins and their plant-derived masked metabolites. The fate of masked mycotoxins in the human gut is poorly understood. Here we assess the metabolism and transport of glucoside metabolites of common trichothecenes (deoxynivalenol, nivalenol, T-2 toxin) and zearalenone compounds (zearalenone, α- and β-zearalenol) in the human gut in vitro.Methods and ResultsMasked mycotoxins were incubated with artificial digestive juices and absorption was assessed in differentiated Caco-2/TC7 cells. Colonic metabolism was studied using fecal batch cultures from 5 donors and mycotoxins were detected using LC-MS/MS. All masked mycotoxins were stable under upper GI tract conditions and no absorption was observed. Free trichothecenes were absorbed intact whereas free zearalenone compounds were absorbed and metabolized to undetected compounds by Caco-2/TC7 cells. Human gut microbiota efficiently hydrolyzed all masked mycotoxins. Trichothecenes were fully recovered as parent mycotoxins whereas 40–70{\%} of zearalenone compounds were further metabolized to unknown metabolites.ConclusionOur results demonstrate that masked trichothecenes will reach the colon intact to be released as parent mycotoxins by gut microbiota, hence contributing to mycotoxin exposure. Masked zearalenone compounds are metabolized by gut microbiota and epithelial cells and the identity and toxicity of metabolites remain to be determined.",
keywords = "Caco-2, deoxynivalenol, glucoside, hydrolysis, nivalenol, HT-2 toxin",
author = "Gratz, {Silvia W.} and Reshma Dinesh and Tomoya Yoshinari and Grietje Holtrop and Richardson, {Anthony J.} and Gary Duncan and Susan MacDonald and Antony Lloyd and Jonathan Farbin",
note = "Acknowledgements This study was funded by the Food Standards Agency UK (FS 102101). The contributions of GH and AJR were funded by the Rural and Environment Science and Analytical Services Division (RESAS) of the Scottish Government.",
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T1 - Masked trichothecene and zearalenone mycotoxins withstand digestion and absorption in the upper GI tract but are efficiently hydrolyzed by human gut microbiota in vitro

AU - Gratz, Silvia W.

AU - Dinesh, Reshma

AU - Yoshinari, Tomoya

AU - Holtrop, Grietje

AU - Richardson, Anthony J.

AU - Duncan, Gary

AU - MacDonald, Susan

AU - Lloyd, Antony

AU - Farbin, Jonathan

N1 - Acknowledgements This study was funded by the Food Standards Agency UK (FS 102101). The contributions of GH and AJR were funded by the Rural and Environment Science and Analytical Services Division (RESAS) of the Scottish Government.

PY - 2017/4

Y1 - 2017/4

N2 - ScopeCereal grains are commonly contaminated with Fusarium mycotoxins and their plant-derived masked metabolites. The fate of masked mycotoxins in the human gut is poorly understood. Here we assess the metabolism and transport of glucoside metabolites of common trichothecenes (deoxynivalenol, nivalenol, T-2 toxin) and zearalenone compounds (zearalenone, α- and β-zearalenol) in the human gut in vitro.Methods and ResultsMasked mycotoxins were incubated with artificial digestive juices and absorption was assessed in differentiated Caco-2/TC7 cells. Colonic metabolism was studied using fecal batch cultures from 5 donors and mycotoxins were detected using LC-MS/MS. All masked mycotoxins were stable under upper GI tract conditions and no absorption was observed. Free trichothecenes were absorbed intact whereas free zearalenone compounds were absorbed and metabolized to undetected compounds by Caco-2/TC7 cells. Human gut microbiota efficiently hydrolyzed all masked mycotoxins. Trichothecenes were fully recovered as parent mycotoxins whereas 40–70% of zearalenone compounds were further metabolized to unknown metabolites.ConclusionOur results demonstrate that masked trichothecenes will reach the colon intact to be released as parent mycotoxins by gut microbiota, hence contributing to mycotoxin exposure. Masked zearalenone compounds are metabolized by gut microbiota and epithelial cells and the identity and toxicity of metabolites remain to be determined.

AB - ScopeCereal grains are commonly contaminated with Fusarium mycotoxins and their plant-derived masked metabolites. The fate of masked mycotoxins in the human gut is poorly understood. Here we assess the metabolism and transport of glucoside metabolites of common trichothecenes (deoxynivalenol, nivalenol, T-2 toxin) and zearalenone compounds (zearalenone, α- and β-zearalenol) in the human gut in vitro.Methods and ResultsMasked mycotoxins were incubated with artificial digestive juices and absorption was assessed in differentiated Caco-2/TC7 cells. Colonic metabolism was studied using fecal batch cultures from 5 donors and mycotoxins were detected using LC-MS/MS. All masked mycotoxins were stable under upper GI tract conditions and no absorption was observed. Free trichothecenes were absorbed intact whereas free zearalenone compounds were absorbed and metabolized to undetected compounds by Caco-2/TC7 cells. Human gut microbiota efficiently hydrolyzed all masked mycotoxins. Trichothecenes were fully recovered as parent mycotoxins whereas 40–70% of zearalenone compounds were further metabolized to unknown metabolites.ConclusionOur results demonstrate that masked trichothecenes will reach the colon intact to be released as parent mycotoxins by gut microbiota, hence contributing to mycotoxin exposure. Masked zearalenone compounds are metabolized by gut microbiota and epithelial cells and the identity and toxicity of metabolites remain to be determined.

KW - Caco-2

KW - deoxynivalenol

KW - glucoside

KW - hydrolysis

KW - nivalenol

KW - HT-2 toxin

U2 - 10.1002/mnfr.201600680

DO - 10.1002/mnfr.201600680

M3 - Article

VL - 61

JO - Molecular Nutrition & Food Research

JF - Molecular Nutrition & Food Research

SN - 1613-4125

IS - 4

M1 - 1600680

ER -