Dietary and Microbial Oxazoles Induce Intestinal Inflammation by Modulating Aryl Hydrocarbon Receptor Responses.

Genome-wide association studies have identified risk loci associated with the development of inflammatory bowel disease, while epidemiological studies have emphasized that pathogenesis likely involves host interactions with environmental elements whose source and structure need to be defined. Here, we identify a class of compounds derived from dietary, microbial, and industrial sources that are characterized by the presence of a five-membered oxazole ring and induce CD1d-dependent intestinal inflammation. We observe that minimal oxazole structures modulate natural killer T cell-dependent inflammation by regulating lipid antigen presentation by CD1d on intestinal epithelial cells (IECs). CD1d-restricted production of interleukin 10 by IECs is limited through activity of the aryl hydrocarbon receptor (AhR) pathway in response to oxazole induction of tryptophan metabolites. As such, the depletion of the AhR in the intestinal epithelium abrogates oxazole-induced inflammation. In summary, we identify environmentally derived oxazoles as triggers of CD1d-dependent intestinal inflammatory responses that occur via activation of the AhR in the intestinal epithelium.

An association between dietary arachidonic acid, measured in adipose tissue, and ulcerative colitis.

BACKGROUND & AIMS: Dietary arachidonic acid, an n-6 polyunsaturated fatty acid (n-6 PUFA), might be involved in the etiology of ulcerative colitis (UC). We performed a prospective cohort study to determine whether high levels of arachidonic acid in adipose tissue samples (which reflects dietary intake) are associated with UC. METHODS: We analyzed data collected from 57,053 men and women in the EPIC-Denmark Prospective Cohort Study from 1993 to 1997. Adipose tissue biopsy samples were collected from gluteal regions at the beginning of the study, the cohort was monitored over subsequent years, and participants who developed UC were identified. A subcohort of 2510 randomly selected participants were used as controls. Concentrations of arachidonic acid were measured in adipose tissue samples. In the analysis, arachidonic acid levels were divided into quartiles; relative risks (RR) were calculated and adjusted for smoking, use of aspirin and nonsteroidal anti-inflammatory drugs, and levels of n-3 PUFAs. RESULTS: A total of 34 subjects (56% men) developed incident UC at a median age of 58.8 years (range, 50.0-69.0 years). Those in the highest quartile for arachidonic acid concentrations in adipose tissue had an RR for UC of 4.16 (95% confidence interval [CI]: 1.56-11.04); a trend per 0.1% increase in arachidonic acid of 1.77 in RR was observed (95% CI: 1.38-2.27). The fraction attributed the highest levels of arachidonic acid was 40.3%. CONCLUSIONS: Individuals with the highest relative concentrations of arachidonic acid in adipose tissue have a significantly greater risk of developing UC. Dietary modifications might therefore prevent UC or reduce disease symptoms.

The Transition of the Gastrointestinal Patient from Pediatric to Adult Care.

Transition is the long process of developing independent self-management skills whereas transfer is the actual move from pediatric to adult-centered provider. Structured anticipated transition works best with timelines of tasks to master and discussion of the stylistic differences between pediatric and adult practices. Disease-specific issues need to be addressed, such as earlier timelines for diet-based therapies, parental support for critical illnesses, and differences in therapeutic strategies.

Transition of the patient with IBD from pediatric to adult care-an assessment of current evidence.

Inflammatory bowel disease is a chronic disease of remitting and relapsing nature that is increasingly diagnosed in childhood or adolescence. The importance of the transition from pediatric to adult health care is increasingly recognized, yet the preparation of patient and family before transfer and early subsequent care in the adult health care environment can be variable and challenging. Pediatric providers need to start early and prepare patients in a stepwise fashion. However, patients may not have mastered all the steps before transfer or may regress to earlier behaviors during stress. Thus, adult providers will need to understand how to maintain and finish the transition process. This is an updated literature review of the transition process in inflammatory bowel disease, which focuses on the practical ways that both pediatric and adult health care providers can optimize care.

Dietary arachidonic and oleic acid intake in ulcerative colitis etiology: a prospective cohort study using 7-day food diaries.

INTRODUCTION: Dietary fatty acids may be involved in the etiology of ulcerative colitis (UC). Arachidonic acid (AA), an n-6 polyunsaturated fatty acid, is a precursor of the proinflammatory cytokines prostaglandin E2 and leukotriene B4, and its metabolism is competitively inhibited by oleic acid (OA). This study aimed to prospectively investigate whether AA is positively and OA is negatively associated with incident UC development, using data from 7-day food diaries. METHODS: A total of 25 639 men and women, aged between 40 and 79 years, from Norfolk, UK, were recruited into the prospective European Prospective Investigation into Cancer (EPIC)-Norfolk cohort between 1993 and 1997. At baseline, participants completed 7-day food diaries, checked by nutritionists using a database containing 11 000 foods and 55 000 portion sizes. The cohort was monitored until June 2004 to identify participants who developed UC. Each patient was matched for age and sex with four controls, and conditional logistic regression was used to calculate adjusted odds ratios for AA and OA intakes, and UC association. RESULTS: Of the participants, 26 (58% men) developed incident UC (53% left sided) after a median follow-up time of 3.8 years (0.5-8.3 years). The highest AA tertile was positively associated with an odds ratio of 6.09 [95% confidence interval (CI) 1.05-35.23], with a trend across tertiles [odds ratio (OR) 2.43, 95% CI 1.06-5.61, P=0.04]. The highest tertile of OA intake was inversely associated with a 0.03 OR for UC (95% CI 0.002-0.56) and an inverse trend (OR 0.30, 95% CI 0.10-0.90, P=0.03). CONCLUSION: Dietary AA was positively and OA was inversely associated with UC development, with large effect sizes in a dose-dependent manner. This supports roles for measuring these nutrients in future etiological studies and modifying intake in future interventional studies in patients with established disease.