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Background/Objectives: The role of long-term alcohol consumption for the risk of developing ulcerative colitis (UC) and Crohn's disease (CD) is unclear. For the first time, to prospectively assess the role of pre-disease alcohol consumption on the risk of developing UC or CD. Subjects/Methods: Nested within the European Prospective Investigation into Cancer and Nutrition (EPIC-IBD), incident UC and CD cases and matched controls where included. At recruitment, participants completed validated food frequency and lifestyle questionnaires. Alcohol consumption was classified as either: non-use, former, light ([[less-than or slanted equal to]0.5 and 1 drink per week), below the recommended limits (BRL) ([[less-than or slanted equal to]1 and 2 drinks per day), moderate ([[less-than or slanted equal to]2.5 and 5 drinks per day), or heavy use (>2.5 and >5 drinks per day) for women and men, respectively; and was expressed as consumption at enrolment and during lifetime. Conditional logistic regression was applied adjusting for smoking and education, taking light users as the reference. Results: Out of 262 451 participants in six countries, 198 UC incident cases/792 controls and 84 CD cases/336 controls were included. At enrolment, 8%/27%/32%/23%/11% UC cases and 7%/29%/40%/19%/5% CD cases were: non-users, light, BRL, moderate and heavy users, respectively. The corresponding figures for lifetime non-use, former, light, BRL, moderate and heavy use were: 3%/5%/23%/44%/19%/6% and 5%/2%/25%/44%/23%/1% for UC and CD cases, respectively. There were no associations between any categories of alcohol consumption and risk of UC or CD in the unadjusted and adjusted odds ratios. Conclusion: There was no evidence of associations between alcohol use and the odds of developing either UC or CD., Author(s): M M Bergmann [sup.1] , V Hernandez [sup.1] [sup.2] , W Bernigau [sup.1] , H Boeing [sup.1] , S S M Chan [sup.3] [sup.4] , R Luben [sup.5] , [...]

Botulism is a neuroparalytic condition, typified by cranial nerve palsies that may be followed by descending symmetrical flaccid paralysis, which can lead to respiratory arrest and, in some instances, death [...]

Mutations in the NOD2 gene are strong genetic risk factors for ileal Crohn's disease. However, the mechanism by which these mutations predispose to intestinal inflammation remains a subject of controversy. We report that Nod2-deficient mice inoculated with Helicobacter hepaticus, an opportunistic pathogenic bacterium, developed granulomatous inflammation of the ileum, characterized by an increased expression of Th1-related genes and inflammatory cytokines. The Peyer's patches and mesenteric lymph nodes were markedly enlarged with expansion of IFN-[gamma]-producing CD4 and CD8 T cells. Rip2-deficient mice exhibited a similar phenotype, suggesting that Nod2 function likely depends on the Rip2 kinase in this model. Transferring wild-type bone marrow cells into irradiated Nod2-deficient mice did not rescue the phenotype. However, restoring crypt antimicrobial function of Nod2-deficient mice by transgenic expression of [alpha]-defensin in Paneth cells rescued the Th1 inflammatory phenotype. Therefore, through the regulation of intestinal microbes, Nod2 function in nonhematopoietic cells of the small intestinal crypts is critical for protecting mice from a Th1-driven granulomatous inflammation in the ileum. The model may provide insight into Nod2 function relevant to inflammation of ileal Crohn's disease. Crohn's disease | granulorna | Helicobacter hepaticus | innate immunity | Paneth cells doi/ 10.1073/pnas.1003363107

Intestinal macrophages play a central role in regulation of immune responses against commensal bacteria. In general, intestinal macrophages lack the expression of innate-immune receptor CD14 and do not produce proinflammatory cytokines against commensal bacteria. In this study, we identified what we believe to be a unique macrophage subset in human intestine. This subset expressed both macrophage (CD14, CD33, CD68) and DC markers (CD205, CD209) and produced larger amounts of proinflammatory cytokines, such as IL-23, TNF-[alpha], and IL-6, than typical intestinal resident macrophages ([CD14.sup.-][CD33.sup.+] macrophages). In patients with Crohn disease (CD), the number of these [CD14.sup.+] macrophages were significantly increased compared with normal control subjects. In addition to increased numbers of cells, these cells also produced larger amounts of IL-23 and TNF-[alpha] compared with those in normal controls or patients with ulcerative colitis. In addition, the [CD14.sup.+] macrophages contributed to IFN-[gamma] production rather than IL-17 production by lamina propria mononuclear cells (LPMCs) dependent on IL-23 and TNF-[alpha]. Furthermore, the IFN-[gamma] produced by LPMCs triggered further abnormal macrophage differentiation with an IL-23-hyperproducing phenotype. Collectively, these data suggest that this IL-23/IFN-[gamma]--positive feedback loop induced by abnormal intestinal macrophages contributes to the pathogenesis of chronic intestinal inflammation in patients with CD., Introduction Although the precise etiologies of inflammatory bowel diseases (IBDs), including Crohn disease (CD) and ulcerative colitis (UC), remain unclear, several reports have indicated that dysfunction of the mucosal immune [...]

Two tests to examine the effectiveness of omega-3 free fatty acids in reducing the rate of relapse of Crohn disease were conducted. Results concluded that omega-3 fatty acids are not effective in reducing rate of relapse in patients with Crohn disease.

Background/Objectives: The role of long-term alcohol consumption for the risk of developing ulcerative colitis (UC) and Crohn%apos;s disease (CD) is unclear. For the first time, to prospectively assess the role of pre-disease alcohol consumption on the risk of developing UC or CD. Subjects/Methods: Nested within the European Prospective Investigation into Cancer and Nutrition (EPIC-IBD), incident UC and CD cases and matched controls where included. At recruitment, participants completed validated food frequency and lifestyle questionnaires. Alcohol consumption was classified as either: non-use, former, light ([precedes/equal to]0.5 and 1 drink per week), below the recommended limits (BRL) ([precedes/equal to]1 and 2 drinks per day), moderate ([precedes/equal to]2.5 and 5 drinks per day), or heavy use ( [greater than] 2.5 and [greater than] 5 drinks per day) for women and men, respectively; and was expressed as consumption at enrolment and during lifetime. Conditional logistic regression was applied adjusting for smoking and education, taking light users as the reference. Results: Out of 262 451 participants in six countries, 198 UC incident cases/792 controls and 84 CD cases/336 controls were included. At enrolment, 8%/27%/32%/23%/11% UC cases and 7%/29%/40%/19%/5% CD cases were: non-users, light, BRL, moderate and heavy users, respectively. The corresponding figures for lifetime non-use, former, light, BRL, moderate and heavy use were: 3%/5%/23%/44%/19%/6% and 5%/2%/25%/44%/23%/1% for UC and CD cases, respectively. There were no associations between any categories of alcohol consumption and risk of UC or CD in the unadjusted and adjusted odds ratios. Conclusion: There was no evidence of associations between alcohol use and the odds of developing either UC or CD. European Journal of Clinical Nutrition (2017) 71, 512-518; doi: 10.1038/ejcn.2016.271; published online 25 January 2017, Author(s): M M Bergmann [1]; V Hernandez [1, 2]; W Bernigau [1]; H Boeing [1]; S S M Chan [3, 4]; R Luben [5]; K-T Khaw [5]; F van Schaik [...]

The two primary human inflammatory bowel diseases, Crohn's disease (CD) and ulcerative colitis (UC), are idiopathic relapsing disorders characterized by chronic inflammation of the intestinal tract. Although several lines of reasoning suggest that gastrointestinal (GI) microbes influence inflammatory bowel disease (IBD) pathogenesis, the types of microbes involved have not been adequately described. Here we report the results of a culture-independent rRNA sequence analysis of GI tissue samples obtained from CD and UC patients, as well as non-IBD controls. Specimens were obtained through surgery from a variety of intestinal sites and included both pathologically normal and abnormal states. Our results provide comprehensive molecular-based analysis of the microbiota of the human small intestine. Comparison of clone libraries reveals statistically significant differences between the microbiotas of CD and UC patients and those of non-IBD controls. Significantly, our results indicate that a subset of CD and UC samples contained abnormal GI microbiotas, characterized by depletion of commensal bacteria, notably members of the phyla Firmicutes and Bacteroidetes. Patient stratification by GI microbiota provides further evidence that CD represents a spectrum of disease states and suggests that treatment of some forms of IBD may be facilitated by redress of the detected microbiological imbalances. Crohn's disease | culture-independent microbiology | ulcerative colitis | rRNA

The inflammatory bowel diseases (IBD) are constituted of two major subphenotypes, that is Crohn's disease (CD) and ulcerative colitis (UC). Lately, the association of Nod2 (CARD15) polymorphisms with CD was established, and taken together, the Nod2 association to CD provides an illustrative model of the role of the single gene variants in disease pathogenesis for common, complex multigene disorders. General features of IBD genetics with particular focus on the role of Nod2 in CD, are reviewed.

BACKGROUND. Growth failure is a recognized complication of pediatric-onset Crohn's disease, but there are few data on final adult height. OBJECTIVE. Our purpose with this work was to determine adult height and the clinical features that influence long-term growth impairment. METHODS. We retrospectively studied 123 patients with Crohn's disease (65 male and 58 female) who had reached adult height. All of the case subjects were diagnosed before age 16.0 years. Heights were converted to SD scores and univariate analysis performed of factors postulated to influence final height, that is, interval from onset of symptoms to diagnosis, prepubertal onset of symptoms, gender, jejunal disease present at diagnosis, systemic steroid therapy, intestinal surgery, and midparental height SD scores. Significant univariate factors were additional analyzed in regression models. RESULTS. Mean height deficit at diagnosis was -0.50 SD scores, which improved to -0.29 SD scores at final height. Mean final height compared with target height, calculated from parental height, was -2.4 cm (range: -20.0 to 9.0 cm). Nineteen percent of the case subjects achieved a final height >8.0 cm below target height. The length of the interval between symptom onset and diagnosis correlated negatively with height SD scores at diagnosis. Height SD scores at diagnosis were related to final height SD scores, independent of midparental height. The presence of jejunal disease was negatively related to final height. CONCLUSIONS. Mean final adult height showed a modest deficit compared with target height, but in one fifth of patients, final height was significantly less than target height. Earlier diagnosis and improved treatment of jejunal disease would be likely to improve final height. www.pediatrics.org/cgi/doi/10.1542/ peds.2005-2931 doi:10.1542/peds.2005-2931 Key Words adult outcomes, Crohn's disease, height Abbreviations SDS--SD score MPH--midparental height CI--confidence interval OR--odds ratio, GROWTH IMPAIRMENT HAS been recognized as a complication of Crohn's disease (1,2) since the earliest descriptions of the disorder in children. (3,4) Short stature and concerns about adult height may [...]

Lung lesions in children with Crohn's disease are often difficult to diagnose and treat. We report here 3 children (aged 13, 14, and 17 years) on immunosuppressive therapy for previously diagnosed Crohn's disease who presented with nonresolving pneumonias. All 3 had unfavorable response to empiric antibiotics and had progression of lesions. Cultures of sputum and blood did not yield any organisms. Subsequent lung biopsies revealed noncaseating granulomas with giant cells in 2 subjects and bronchiolitis obliterans with organizing pneumonia in the third. All patients were treated with infliximab, a novel anti-tumor necrosis factor monoclonal antibody, and showed rapid clinical and radiologic response. We emphasize that a high index of suspicion for noninfectious etiologies needs to be maintained in patients with Crohn's disease who present with lung lesions to ensure timely intervention. Infliximab therapy seems to be effective and well tolerated in such patients. Abbreviations: IBD, inflammatory bowel disease; CT, computed tomography, Short communications of factual material are published here. Comments and criticisms appear as Commentaries or Letters to the Editor. "In Medicine one must pay attention not to plausible theorizing but […]

The pathogenesis of Crohn's disease (CD), an idiopathic inflammatory bowel disease, is attributed, in part, to intestinal bacteria that may initiate and perpetuate mucosal inflammation in genetically susceptible individuals. Paneth cells (PC) are the major source of antimicrobial peptides in the small intestine, including human [alpha]-defensins HD5 and HD6. We tested the hypothesis that reduced expression of PC [alpha]-defensins compromises mucosal host defenses and predisposes patients to CD of the ileum. We report that patients with CD of the ileum have reduced antibacterial activity in their intestinal mucosal extracts. These specimens also showed decreased expression of PC [alpha]-defensins, whereas the expression of eight other PC products either remained unchanged or increased when compared with controls. The specific decrease of [alpha]-defensins was independent of the degree of inflammation in the specimens and was not observed in either CD of the colon, ulcerative colitis, or pouchitis. The functional consequence of [alpha]-defensin expression levels was examined by using a transgenic mouse model, where we found changes in HD5 expression levels, comparable to those observed in CD, had a pronounced impact on the luminal microbiota. Thus, the specific deficiency of PC defensins that characterizes ileal CD may compromise innate immune defenses of the ileal mucosa and initiate and/or perpetuate this disease. innate immunity | intestine | bacteria | inflammatory bowel disease

Background. Delayed growth is a well-established feature of pediatric Crohn's disease. Several factors have been shown to affect growth, including disease location, severity, and treatment. The recently discovered NOD2 gene has been correlated to ileal location of Crohn's disease and subsequently could affect growth through the resulting phenotype or as an independent risk factor. The aim of our study was to determine if growth retardation is affected by genotype independently of disease location or severity. Methods. Genotyping for 3 NOD2 single-nucleotide polymorphisms was performed in 93 patients with detailed growth records. Parameters including disease location, disease severity, and NOD 2 genotype and their effect on z scores for height and weight at disease onset and during follow-up were analyzed. Results. NOD2 mutations were correlated with ileal location but not with disease severity or growth retardation. Ileal involvement was significantly associated with height retardation at disease onset and the lowest z score during follow-up. Use of steroids affected weight but not height. Regression models for growth variables revealed that the strongest association with impaired growth is with disease severity (weight- and height-failure odds ratios: 6.17 and 4.52, respectively). Conclusions. Severity of disease is correlated with growth failure for both height and weight. Location of disease is a weaker predictor of disordered growth and is correlated with growth retardation but not growth failure. The NOD2 genotype was not correlated with growth retardation or growth failure. Pediatrics 2004;114:1281-1286; NOD2, height failure, weight failure, Crohn's disease, growth, inflammatory bowel disease, genes, pediatric., ABBREVIATIONS. CD, Crohn's disease; SNP, single-nucleotide polymorphism; PCR, polymerase chain reaction; OR, odds ratio; CI, 95% confidence interval Growth retardation is a frequent feature of pediatric Crohn's disease (CD). Up [...]

The trends in the incidence of inflammatory bowel disease (IBD) are examined over a period of 12 year from 1988 to 1999 in areas of Northern France. The incidence of Crohn's disease increased by 23 percent and the incidence of ulcerative colitis (UC) declined by 17 percent during the 12 years.

Author(s): Manuela M. Bergmann [sup.1] , Vicent Hernandez [sup.2] , Andrew Hart [sup.3] [sup.4] Author Affiliations: (1) Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbrücke, Potsdam, Germany (2) Department [...]

Inflammatory bowel disease (IBD) is a general term for inflammation of the ileum (Crohn's disease) or colon (ulcerative colitis) resulting in pain, malabsorption of nutrients, diarrhea, bleeding, and other symptoms. The causal factors involved in the onset of IBD are not known, but it is thought that many environmental conditions may increase or decrease the likelihood of developing this disease. Cigarette smoking has been linked to the development of IBD, but the data are contradictory and confusing. Cigarette smokers are reported to be more likely to develop Crohn's disease than nonsmokers, but less likely to develop ulcerative colitis than nonsmokers. To further investigate the relationship between smoking and IBD, a case-control study was carried out in Sweden, between 1984 and 1987, which examined the influence of smoking and of childhood exposure to cigarette smoke on the prevalence of IBD. Information was collected using questionnaires completed by 152 Crohn's disease patients, 145 ulcerative colitis patients, and 305 respondents with no diagnosed gastrointestinal disease. The risk of developing Crohn's disease was greater in patients who had been exposed to cigarette smoke as children; there was no effect of childhood environmental smoke on predilection towards ulcerative colitis. The risk of developing ulcerative colitis was greater in smokers who had recently quit than it was in patients who had never smoked. Data on additional subgroups are also reported and discussed. (Consumer Summary produced by Reliance Medical Information, Inc.)

Byline: Eduardo Cueto Rua (1), Norma Blacarce (1), Ricardo Drut (2) Author Affiliation: (1) Gastroenterology Unit, Hospital de Ninos 'Superiora Sor Maria Ludovica', 1900 La Plata, Argentina, AR (2) Department of Pathology, Hospital de Ninos 'Superiora Sor Maria Ludovica', 1900 La Plata, Argentina, AR