Toxicity Mechanisms of Wheat and Other Cereals in Celiac Disease and Related Enteropathies

Auricchio, Salvatore; G, De Ritis; M, De Vincenzi; Silano,

doi:10.1097/00005176-198512000-00012

Cited by 31 publications

(13 citation statements)

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Section: Studies On Cereal Peptides With Cultured Intestinal Biopsiesmentioning

confidence: 99%

“…It is not clear whether these discrepancies depend on the use in some studies of biochemical markers versus the use in other studies of morphological and morphometric parameters to assess the status of the intestinal mucosa or rather on the possibility that for the coeliac mucosa in remission there is a time lag before in vitro toxic effects of gliadin peptides may show up [93] which depends on the "degree of remission" of the mucosa specimens tested. The latter hypothesis is also supported by the fact that when the data of Falchuk et al [73] showing the absence of effects of gluten peptides on treated coeliac mucosa, were re-evaluated by Auricchio et al [93] it appeared that specimens with a lower initial alkaline phosphatase level (i. e. less recovered) were susceptible to toxic effects of gluten peptides, whereas those with a higher initial level of alkaline phosphatase (i. e. more recovered) were not, although all were derived from a mucosa in remission. Moreover, the fact that, when mucosal tissue samples from patients with active and inactive coeliac disease were co-cultured, gliadin affected both cultures, does not necessarily imply that gliadin peptides are not directly toxic to epithelial cells of coeliac mucosa and require the activation of an endogenous effector mechanism diffusible through the culture medium, [66], but may also depend on a binding of gliadin peptides to coeliac mucosa in remission resulting in a cytostatic effect making epithelial cells more susceptible to the effects of killer cells (e. g., lymphocytes) coming from the atrophic mucosa fragments.…”

Section: Studies On Cereal Peptides With Cultured Intestinal Biopsiesmentioning

confidence: 99%

“…Thus, although the involvement of the immune system in gluten-dependent entheropaties is well established, it cannot be excluded, in our opinion, a very important role in these entheropathies of a genetically-determined or otherwise induced appearance of immature (relatively undifferentiated) enterocytes on the intestinal mucosa on which toxic gliadin peptides act in a lectin-like manner. Furthermore, the glutenlecting hypothesis [93] can also provide a theoretical background to explain the fiindings by Doherty and Barry [125], who showed that, to develop intestinal lesion, healthy relatives require higher amounts of gluten than coeliac patients, thus indicating gluten sensitivity as a dose-dependent phenomenon. Similarly, the gluten-lectin hypothesis can more easily explain the results concerning substances such as mannan, oligomers of N-acetyl-glucosamine and poly-cationic polyamines, which have been found able to interfere with and even to reverse the expression of biological activities of "toxic" prolamine peptides on atrophic mucosa, immature intestines and undifferentiated cells.…”

Section: Mechanisms Of Actionmentioning

confidence: 99%

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Bioactive antinutritional peptides derived from cereal prolamins: A Review

Silano

Vincenzi

1999

Nahrung

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Alcohol-soluble endosperm proteins (prolamins) from some cereals (e.g. wheat, barley, and rye) give origin upon proteolytic digestion to biologically-active antinutritional peptides able to adversely affect in vivo the intestinal mucosa of coeliac patients, whereas prolamins from other cereals (e.g. maize and rice) do not. These antinutritional peptides are also able to: (a) prevent in vitro recovery of atrophic coeliac mucosa; (b) to inhibit differentiation of isolated rat fetal and chick fetal intestines; and (c) to interact with undifferentiated cells either agglutinating them or affecting their proliferation and metabolism. Studies performed with A-gliadin, a highly purified bread wheat prolamin fraction, and its fragments obtained either by chemical cleavage of A-gliadin or by synthesis from aminoacids, clearly pointed out to a few small sequences very rich in glutamine and proline residues as the biologically-active agents. Several protective substances, including mannan and N,N',N"-triacetylchitotriose, have been identified as being able to prevent the effects of these peptides in vitro, but the evidence of their in vivo activity is still missing. The present paper provides a synthetic overview of the available data concerning this highly complex matter and offers a critical appraisal of present hypotheses on the action mechanism of biologically-active peptides derived from cereal prolamins.

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Section: Studies On Cereal Peptides With Cultured Intestinal Biopsiesmentioning

confidence: 99%

Section: Studies On Cereal Peptides With Cultured Intestinal Biopsiesmentioning

confidence: 99%

Section: Mechanisms Of Actionmentioning

confidence: 99%

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Bioactive antinutritional peptides derived from cereal prolamins: A Review

Silano

Vincenzi

1999

Nahrung

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“…A 33-mer peptide was shown to be a potent inducer of gutderived human T-cell lines in 14 of 14 CS patients (40). Other peptides, such as fragment 31-43 of A-gliadin, caused an inflammatory response of the small intestinal mucosa (5,8,36) without a T-cell-mediated response (35). The large proportion and location of proline residues in the amino acid sequences of these toxic peptides make them extremely resistant to further proteolysis (2,11,27).…”

mentioning

confidence: 99%

Sourdough Bread Made from Wheat and Nontoxic Flours and Started with Selected Lactobacilli Is Tolerated in Celiac Sprue Patients

Cagno

Angelis

Auricchio

et al. 2004

Appl Environ Microbiol

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236

158

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This work was aimed at producing a sourdough bread that is tolerated by celiac sprue (CS) patients. Selected sourdough lactobacilli had specialized peptidases capable of hydrolyzing Pro-rich peptides, including the 33-mer peptide, the most potent inducer of gut-derived human T-cell lines in CS patients. This epitope, the most important in CS, was hydrolyzed completely after treatment with cells and their cytoplasmic extracts (CE). A sourdough made from a mixture of wheat (30%) and nontoxic oat, millet, and buckwheat flours was started with lactobacilli. After 24 h of fermentation, wheat gliadins and low-molecular-mass, alcohol-soluble polypeptides were hydrolyzed almost totally. Proteins were extracted from sourdough and used to produce a peptictryptic digest for in vitro agglutination tests on K 562(S) subclone cells of human origin. The minimal agglutinating activity was ca. 250 times higher than that of doughs chemically acidified or started with baker's yeast. Two types of bread, containing ca. 2 g of gluten, were produced with baker's yeast or lactobacilli and CE and used for an in vivo double-blind acute challenge of CS patients. Thirteen of the 17 patients showed a marked alteration of intestinal permeability after ingestion of baker's yeast bread. When fed the sourdough bread, the same 13 patients had values for excreted rhamnose and lactulose that did not differ significantly from the baseline values. The other 4 of the 17 CS patients did not respond to gluten after ingesting the baker's yeast or sourdough bread. These results showed that a bread biotechnology that uses selected lactobacilli, nontoxic flours, and a long fermentation time is a novel tool for decreasing the level of gluten intolerance in humans.

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“…Among these systems, agglutination of in vitro cultured human myelogenous leukemia K 562(S) cells proved to be a suitable model for detection of toxic components (11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21). In fact, very low concentrations of peptic-tryptic (PT) digests of gliadins and prolamins from rye, barley, and oat were shown to be able to agglutinate the K 562(S) cells, whereas nontoxic peptides (albumin and globulin of wheat and prolamins from rice and maize) proved to be inactive.…”

Section: Introductionmentioning

confidence: 99%