Naturally-occurring dietary salicylates in the genesis of functional gastrointestinal symptoms in patients with irritable bowel syndrome: Pilot study.

BACKGROUND AND AIM: An elimination-rechallenge dietary approach targeting naturally-occurring bioactive chemicals has been proposed to alleviate functional gastrointestinal symptoms. A major focus of this approach is salicylates. This study aimed to address the potential role of dietary salicylates in the induction of symptoms in patients with irritable bowel syndrome (IBS). METHODS: A pilot, double-blind, randomized, cross-over trial of 2-week low- versus high-salicylate diets (6.6 and 27.9 g/day salicylate, respectively) was undertaken. All foods were provided containing minimal quantities of other potential food triggers. Gastrointestinal and extraintestinal symptoms were measured daily using a 100-mm visual-analogue-scale. RESULTS: Ten participants with IBS completed the study, including one with known aspirin-sensitivity. Overall, no differences in symptoms were observed (P = 0.625; Friedman test). However, clear symptom provocation was seen in the aspirin-sensitive participant, with all abdominal symptoms and tiredness worsening during the high-salicylate diet. A similar trend was seen in another participant, where abdominal symptoms gradually worsened during the high-salicylate diet. CONCLUSIONS: These results provide some evidence that food-related salicylates may influence the genesis of symptoms in a subset of patients with IBS. A larger cohort is needed to determine the incidence of salicylate-sensitivity and further evaluate the diet as a potential therapeutic target.The protocol was registered at www.anzctr.org.au (ACTRN12620001250921).

Bioactive food chemicals and gastrointestinal symptoms: a focus of salicylates.

Bioactive food chemicals are substances present in food that are capable of interacting with living cells causing changes in physiological functions. Salicylic acid (SA), a plant hormone involved in plant immune response, is one such bioactive food chemical. Aspirin, a commercially available SA, might play beneficial roles in cardiovascular health and colon cancer. It may also cause urticaria, angioedema, asthma, and gastrointestinal symptoms in SA-sensitive individuals. Dietary SA might exert similar beneficial effects and/or may induce similar symptoms in hypersensitive individuals. Food-related SA sensitivity in relation to gastrointestinal symptoms is not well documented besides a few self-reported questionnaires and the knowledge that low doses of aspirin (equivalent of high dietary intake) can cause gastrointestinal injury. The only direct evidence that suggests benefits of reducing dietary SA was reported in asthmatic individuals. Although SA sensitivity in relation to gut symptoms in susceptible individuals is accepted by clinicians, the detection of this disease remains a challenge because of the complicated nature of dietary challenges and the risk of oral aspirin provocation tests in patients with severe hypersensitivity reactions. Given the non-IgE mediated nature of the disease, in vitro assays like basophil activation may have failed to produce reliable results. However, given the simplicity of this assay, further studies need to be formulated to firmly establish its reliability. Formulation of proper dietary strategies for symptom control is also impossible given the controversial and scant nature of the data on SA content of food. This issue needs to be resolved to formulate proper dietary strategies for effective symptom control.

Food components and irritable bowel syndrome.

Ingestion of food has long been linked with gut symptoms, and there is increasing interest in using diet in the management of patients with irritable bowel syndrome (IBS). The West has developed an intense interest in specialized, restrictive diets, such as those that target multiple food groups, avoid gluten, or reduce fermentable oligo-, di-, and mono-saccharides and polyols. However, most gastroenterologists are not well educated about diets or their effects on the gut. It is important to understand the various dietary approaches, their putative mechanisms, the evidence that supports their use, and the benefits or harm they might produce. The concepts behind, and delivery of, specialized diets differ from those of pharmacologic agents. High-quality research is needed to determine the efficacy of different dietary approaches and the place of specific strategies.

Williams Syndrome Transcription Factor is critical for neural crest cell function in Xenopus laevis.

Williams Syndrome Transcription Factor (WSTF) is one of ∼25 haplodeficient genes in patients with the complex developmental disorder Williams Syndrome (WS). WS results in visual/spatial processing defects, cognitive impairment, unique behavioral phenotypes, characteristic "elfin" facial features, low muscle tone and heart defects. WSTF exists in several chromatin remodeling complexes and has roles in transcription, replication, and repair. Chromatin remodeling is essential during embryogenesis, but WSTF's role in vertebrate development is poorly characterized. To investigate the developmental role of WSTF, we knocked down WSTF in Xenopus laevis embryos using a morpholino that targets WSTF mRNA. BMP4 shows markedly increased and spatially aberrant expression in WSTF-deficient embryos, while SHH, MRF4, PAX2, EPHA4 and SOX2 expression are severely reduced, coupled with defects in a number of developing embryonic structures and organs. WSTF-deficient embryos display defects in anterior neural development. Induction of the neural crest, measured by expression of the neural crest-specific genes SNAIL and SLUG, is unaffected by WSTF depletion. However, at subsequent stages WSTF knockdown results in a severe defect in neural crest migration and/or maintenance. Consistent with a maintenance defect, WSTF knockdowns display a specific pattern of increased apoptosis at the tailbud stage in regions corresponding to the path of cranial neural crest migration. Our work is the first to describe a role for WSTF in proper neural crest function, and suggests that neural crest defects resulting from WSTF haploinsufficiency may be a major contributor to the pathoembryology of WS.

How many remodelers does it take to make a brain? Diverse and cooperative roles of ATP-dependent chromatin-remodeling complexes in development.

The development of a metazoan from a single-celled zygote to a complex multicellular organism requires elaborate and carefully regulated programs of gene expression. However, the tight packaging of genomic DNA into chromatin makes genes inaccessible to the cellular machinery and must be overcome by the processes of chromatin remodeling; in addition, chromatin remodeling can preferentially silence genes when their expression is not required. One class of chromatin remodelers, ATP-dependent chromatin-remodeling enzymes, can slide nucleosomes along the DNA to make specific DNA sequences accessible or inaccessible to regulators at a particular stage of development. While all ATPases in the SWI2/SNF2 superfamily share the fundamental ability to alter DNA accessibility in chromatin, they do not act alone, but rather, are subunits of a large assortment of protein complexes. Recent studies illuminate common themes by which the subunit compositions of chromatin-remodeling complexes specify the developmental roles that chromatin remodelers play in specific tissues and at specific stages of development, in response to specific signaling pathways and transcription factors. In this review, we will discuss the known roles in metazoan development of 3 major subfamilies of chromatin-remodeling complexes: the SNF2, ISWI, and CHD subfamilies.