Deoxynivalenol: a trigger for intestinal integrity breakdown

Akbari, Peyman; Braber, Saskia; Gremmels, Hendrik; Koelink, Pim J.; Verheijden, Kim A.T.; Garssen, Johan; Fink‐Gremmels, Johanna

doi:10.1096/fj.13-238717

Cited by 127 publications

(172 citation statements)

References 53 publications

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“…In our study , the mycotoxin DON serves as a reliable and reproducible model of intestinal barrier dysfunction [13,19] and a strong positive correlation was observed between IL-33 mRNA expression in the mouse distal small intestine and the intestinal permeability induced by DON. Besides IL-33, the tight and adherens junctions are also critical for the maintenance of intestinal barrier integrity [20,21,22].…”

Section: Discussionmentioning

confidence: 88%

“…To assess intestinal permeability changes, the intestinal permeability to 4 kDa fluorescein isothiocyanate (FITC)-dextran (Sigma-Aldrich, St. Louis, Mo., USA) was measured as described previously [13]. Briefly, 2 h after DON administration, all mice received FITC-dextran (500 mg/kg of body weight) by oral gavage.…”

Section: Methodsmentioning

confidence: 99%

“…Gene expression was determined by quantitative (q)RT-PCR, as described previously [13]. In brief, samples of the distal small intestine and lung tissue were homogenized in RNA lysis buffer with β-mercaptoethanol.…”

Section: Methodsmentioning

confidence: 99%

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Inflammation-Induced Expression of the Alarmin Interleukin 33 Can Be Suppressed by Galacto-Oligosaccharides

Verheijden

Akbari²,

Willemsen³

et al. 2015

Int Arch Allergy Immunol

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Background: The alarmin interleukin 33 (IL-33) and its receptor ST2 play an important role in mucosal barrier tissues, and seem to be crucial for Th2-cell mediated host defense. Galacto-oligosaccharides (GOS), used in infant formulas, exhibit gut and immune modulatory effects. To enhance our understanding of the immunomodulatory capacity of GOS, this study investigated the impact of dietary GOS intervention on IL-33 and ST2 expression related to intestinal barrier dysfunction and asthma. Methods: B6C3F₁ and BALB/c mice were fed a control diet with or without 1% GOS. To simulate intestinal barrier dysfunction, B6C3F₁ mice received a gavage with the mycotoxin deoxynivalenol (DON). To mimic asthma-like inflammatory airway responses, BALB/c mice were sensitized on day 0 and challenged on days 7-11 with house-dust mite (HDM) allergen. Samples from the intestines and lungs were collected for IL-33 and ST2 analysis by qRT-PCR, immunoblotting and immunohistochemistry. Results: Dietary GOS counteracted the DON-induced IL-33 mRNA expression and changed the IL-33 distribution pattern in the mouse small intestine. The IL-33 mRNA expression was positively correlated to the intestinal permeability. A strong positive correlation was also observed between IL-33 mRNA expression in the lung and the number of bronchoalveolar fluid cells. Reduced levels of IL-33 protein, altered IL-33 distribution and reduced ST2 mRNA expression were observed in the lungs of HDM-allergic mice after GOS intervention. Conclusions: Dietary GOS mitigated IL-33 at the mucosal surfaces in a murine model for intestinal barrier dysfunction and HDM-induced asthma. This promising effect may open up new avenues to use GOS not only as a prebiotic in infant nutrition, but also as a functional ingredient that targets inflammatory processes and allergies associated with IL-33 expression.

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Section: Discussionmentioning

confidence: 88%

Section: Methodsmentioning

confidence: 99%

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Inflammation-Induced Expression of the Alarmin Interleukin 33 Can Be Suppressed by Galacto-Oligosaccharides

Verheijden

Akbari²,

Willemsen³

et al. 2015

Int Arch Allergy Immunol

Self Cite

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“…In 1931 extremely high levels of T2 and HT2 in stored grains caused an outbreak of alimentary toxic aleukia (ATA) syndrome in the USSR, with a mortality rate of 60% [35]. Nonetheless, that was the only outbreak of human mycotoxicosis related to trichothecenes ingestion, while more chronic and sub-chronic effects are often related to intestinal disease [36]. Concerning zearalenone and its metabolites, their role as endocrine disruptor is well-known and often related to estrogenic effects in humans [37,38].…”

Section: Adverse Effects Of Mycotoxins On Humansmentioning

confidence: 99%

Mycotoxins and Nuclear Receptors: A Still Underexplored Issue

Dall’Asta¹

2016

Nuclear Receptor Research

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Abstract.Mycotoxins are fungal secondary metabolites that can be found in food commodities worldwide. They exert a wide range of adverse effects towards humans and animals. Although toxicological studies have addressed these food contaminants over decades, their mode of actions as well as their synergistic effects are still to be deeply clarified. Among the toxicological targets, nuclear receptors have been identified by several studies. Besides the estrogenic effect, a wider range of endocrine and neuroendocrine disrupting effects have been reported so far. This review is aimed at addressing the recent advances in toxicology, and at highlighting possible gaps of knowledge.

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“…DON exposure provokes increases in intestinal permeability allowing passage of pathogenic and commensal bacteria from the gut lumen into the systemic circulation [275,276]. This is caused by a suppressed transcription of claudin hence impairing the effectiveness of endothelial tight junctions [276,277].…”

Section: Chronic Mold and Mycotoxin Exposurementioning

confidence: 99%

The Putative Role of Viruses, Bacteria, and Chronic Fungal Biotoxin Exposure in the Genesis of Intractable Fatigue Accompanied by Cognitive and Physical Disability

Morris¹,

Berk

Walder

et al. 2015

Mol Neurobiol

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Patients who present with severe intractable apparently idiopathic fatigue accompanied by profound physical and or cognitive disability present a significant therapeutic challenge. The effect of psychological counseling is limited, with significant but very slight improvements in psychometric measures of fatigue and disability but no improvement on scientific measures of physical impairment compared to controls. Similarly, exercise regimes either produce significant, but practically unimportant, benefit or provoke symptom exacerbation. Many such patients are afforded the exclusionary, non-specific diagnosis of chronic fatigue syndrome if rudimentary testing fails to discover the cause of their symptoms. More sophisticated investigations often reveal the presence of a range of pathogens capable of establishing life-long infections with sophisticated immune evasion strategies, including Parvoviruses, HHV6, variants of Epstein-Barr, Cytomegalovirus, Mycoplasma, and Borrelia burgdorferi. Other patients have a history of chronic fungal or other biotoxin exposure. Herein, we explain the epigenetic factors that may render such individuals susceptible to the chronic pathology induced by such agents, how such agents induce pathology, and, indeed, how such pathology can persist and even amplify even when infections have cleared or when biotoxin exposure has ceased. The presence of active, reactivated, or even latent Herpes virus could be a potential source of intractable fatigue accompanied by profound physical and or cognitive disability in some patients, and the same may be true of persistent Parvovirus B12 and mycoplasma infection. A history of chronic mold exposure is a feasible explanation for such symptoms, as is the presence of B. burgdorferi. The complex tropism, life cycles, genetic variability, and low titer of many of these pathogens makes their detection in blood a challenge. Examination of lymphoid tissue or CSF in such circumstances may be warranted.

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Deoxynivalenol: a trigger for intestinal integrity breakdown

Cited by 127 publications

References 53 publications

Inflammation-Induced Expression of the Alarmin Interleukin 33 Can Be Suppressed by Galacto-Oligosaccharides

Inflammation-Induced Expression of the Alarmin Interleukin 33 Can Be Suppressed by Galacto-Oligosaccharides

Mycotoxins and Nuclear Receptors: A Still Underexplored Issue

The Putative Role of Viruses, Bacteria, and Chronic Fungal Biotoxin Exposure in the Genesis of Intractable Fatigue Accompanied by Cognitive and Physical Disability

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