The role of animal models in unravelling therapeutic targets in coeliac disease

Costes, L M M; Meresse, Bertrand; Cerf‐Bensussan, Nadine; Samsom, Janneke N.

doi:10.1016/j.bpg.2015.04.007

Cited by 11 publications

(7 citation statements)

References 85 publications

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“…Therefore, it could be interesting to investigate whether a diet with inclusion of rye, containing a high concentration of gluten, or other related plant allergens, also influence the calcium concentration in the shell of eggs [33]. If so, measurement of the calcium levels in egg shells may be a relatively straight forward and animal-friendly manner (model) to study the effect of human diets containing gluten or other coeliac-inducing plant allergens on bone demineralisation [15]. …”

Section: Discussionmentioning

confidence: 99%

Enrichment of in vivo transcription data from dietary intervention studies with in vitro data provides improved insight into gene regulation mechanisms in the intestinal mucosa

et al. 2017

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BackgroundGene expression profiles of intestinal mucosa of chickens and pigs fed over long-term periods (days/weeks) with a diet rich in rye and a diet supplemented with zinc, respectively, or of chickens after a one-day amoxicillin treatment of chickens, were recorded recently. Such dietary interventions are frequently used to modulate animal performance or therapeutically for monogastric livestock. In this study, changes in gene expression induced by these three interventions in cultured “Intestinal Porcine Epithelial Cells” (IPEC-J2) recorded after a short-term period of 2 and 6 hours, were compared to the in vivo gene expression profiles in order to evaluate the capability of this in vitro bioassay in predicting in vivo responses.MethodsLists of response genes were analysed with bioinformatics programs to identify common biological pathways induced in vivo as well as in vitro. Furthermore, overlapping genes and pathways were evaluated for possible involvement in the biological processes induced in vivo by datamining and consulting literature.ResultsFor all three interventions, only a limited number of identical genes and a few common biological processes/pathways were found to be affected by the respective interventions. However, several enterocyte-specific regulatory and secreted effector proteins that responded in vitro could be related to processes regulated in vivo, i.e. processes related to mineral absorption, (epithelial) cell adherence and tight junction formation for zinc, microtubule and cytoskeleton integrity for amoxicillin, and cell-cycle progression and mucus production for rye.ConclusionsShort-term gene expression responses to dietary interventions as measured in the in vitro bioassay have a low predictability for long-term responses as measured in the intestinal mucosa in vivo. The short-term responses of a set regulatory and effector genes, as measured in this bioassay, however, provided additional insight into how specific processes in piglets and broilers may be modulated by “early” signalling molecules produced by enterocytes. The relevance of this set of regulatory/effector genes and cognate biological processes for zinc deficiency and supplementation, gluten allergy (rye), and amoxicillin administration in humans is discussed.Electronic supplementary materialThe online version of this article (doi:10.1186/s12263-017-0559-1) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Enrichment of in vivo transcription data from dietary intervention studies with in vitro data provides improved insight into gene regulation mechanisms in the intestinal mucosa

et al. 2017

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“…Given the retrospective nature of our study, it is not possible to determine whether and to what extent the HSCs are contributing directly to the repopulation of depleted ISCs. This hypothesis should be tested in animal models of CD, for instance upon sex-mismatched HSC transplantation [ 28 ].…”

Section: Discussionmentioning

confidence: 99%

Circulating hematopoietic stem cells and putative intestinal stem cells in coeliac disease

et al. 2015

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BackgroundThe intestinal stem cells (ISC) modulation and the role of circulating hematopoietic stem cells (HSC) in coeliac disease (CD) are poorly understood. Our aim was to investigate the longitudinal modifications in peripheral blood HSC traffic and putative ISC density induced by gluten-free diet (GFD) in CD.MethodsThirty-one CD patients and 7 controls were enrolled. Circulating CD133+ and CD34+ HSC were measured by flow cytometry, at enrolment and after 7 days and 1, 3, 6, 12, and 24 months of GFD. Endoscopy was performed at diagnosis and repeated at 6, 12, and 24 months following GFD. We used the Marsh-Oberhuber score to evaluate the histological severity of duodenal damage; immunohistochemistry was employed to measure the intraepithelial lymphoid infiltrate (IEL, CD3+ lymphoid cells) and the putative ISC compartment (CD133+ and Lgr5+ epithelial cells).ResultsAt enrolment, circulating HSCs were significantly increased in CD patients and they further augmented during the first week of GFD, but progressively decreased afterwards. CD patients presented with villous atrophy, abundant IEL and rare ISC residing at the crypt base. Upon GFD, IEL progressively decreased, while ISC density increased, peaking at 12 months. After 24 months of GFD, all patients were asymptomatic and their duodenal mucosa was macroscopically and histologically normal.ConclusionsIn active CD patients, the ISC niche is depleted and there is an increased traffic of circulating HSC versus non-coeliac subjects. GFD induces a precocious mobilization of circulating HSC, which is followed by the expansion of the local ISC compartment, leading to mucosal healing and clinical remission.

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“…Thus, additional knowledge about the effects of individual food additives on the duodenal morphology is necessary and may result in practical output for dietetic indication and preparation of better nutritional products. Some animal models for celiac disease were established and the effects of various diet have been investigated (Costes et al 2015, Ju et al 2015. Moreover, not much is known with regards to the best supplement options as food additive for healthy people.…”

Section: Discussionmentioning

confidence: 99%

The Effect of Selected Feed Mixtures on the Duodenal Morphology: Comparison Study

Makovický

Chrenková²,

Fl’ak³

et al. 2018

Physiol Res

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The objective of this work was to compare the effect of selected feed mixtures on the duodenal morphology. One-hundred-four rats of the Wistar strain were divided to thirteen groups per eight rats. The experiment started in 35-day-old rats after birth and lasted for 32 days. The groups (A-M) were fed by commercial diet, 85 % wheat and 15 % oat diet, 85 % wheat and 15 % triticale, 85 % wheat and 15 % barley, 85 % wheat and 15 % amaranth, 85 % wheat and 15 % lantern, 85 % wheat and 15 % buckwheat, 100 % wheat, 100 % white lupine, 100 % flock peas -variety Garden, 100 % native peas -variety Garden, 100 % native peas -variety Zekon or 100 % extruded peas -variety Zekon diet, respectively. Samples from the duodenum were taken. The height of the villi and the depth of the crypts were measured. The tallest villi were measured in group F (474.33±114.36 µm) and the shortest villi were observed in group B (294.08±88.52 µm). The deepest crypts were measured in group K (166.41±35.69 µm) and the shallowest crypts were observed in group E (77. 85±17.61 µm). The work documents that gluten-free and classical cereals combination can be a better choice for people who want to limit the gluten content of the diet.

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The role of animal models in unravelling therapeutic targets in coeliac disease

Cited by 11 publications

References 85 publications

Enrichment of in vivo transcription data from dietary intervention studies with in vitro data provides improved insight into gene regulation mechanisms in the intestinal mucosa

Enrichment of in vivo transcription data from dietary intervention studies with in vitro data provides improved insight into gene regulation mechanisms in the intestinal mucosa

Circulating hematopoietic stem cells and putative intestinal stem cells in coeliac disease

The Effect of Selected Feed Mixtures on the Duodenal Morphology: Comparison Study

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