Summary
Background
The changing epidemiology of inflammatory bowel disease (IBD) in both the developed and developing worlds may provide insights into disease aetiology. Factors that impact on the ...gut microbiome are leading aetiological candidates.
Aim
To review epidemiological studies and trends that identify risk factors for the development of IBD.
Methods
Studies that identified factors associated with the development of IBD differentially in children and adults were reviewed. There was a focus on epidemiological studies and on studies that involve the gut microbiome.
Results
Use of antibiotics has been shown to be associated with development of Crohn's disease in childhood (odds ratio, OR = 2.75, 95% CI 1.72‐4.38). Breastfeeding has been protective against developing IBD (OR=0.69, 95% CI 0.51‐0.94), but there is a paucity of data exploring duration of breastfeeding and timing of introduction of bottled milk or table food. Antibiotics and diet changes can also impact on adults enhancing the risk for IBD. Both smoking (OR=1.76, 95% CI 1.40‐2.22) and oral contraceptives (relative risk=1.46, 95% CI 1.26‐1.70) increase the risk for Crohn's disease and their use is associated with worse outcomes in Crohn's disease. It is unclear if their impact is mediated through the gut microbiome.
Conclusions
A leading aetiological clue for IBD based on epidemiological studies is the antecedent use of antibiotics both for children and adults. Some dietary changes may be a risk for adults but there is a paucity of dietary data in children prior to IBD development. Both antibiotic use and dietary changes have the potential to impact the gut microbiome, which in turn can alter the gut immune response.
Summary
Background
Proton pump inhibitor (PPI) use is associated with an increased risk of Clostridium difficile infection (CDI), though the mechanism is unclear. PPI induced alterations to the gut ...microbiome may facilitate the emergence of CDI, though the effects of PPIs on gut microbiota are not well characterised. Correction added on 10 March 2016, after first online publication: microflora has been changed to microbiota throughout the article.
Aim
To compare the faecal microbiomes of long‐term PPI users to those with no history of PPI use.
Methods
We used a population‐based database to identify individuals with ≥5 years of continuous PPI use along with non‐PPI using controls. Stool samples were subjected to microbiological analysis, with hierarchical clustering at genus level, along with alpha and beta diversity measures comparing the two groups. Metadata was accounted for using quantile regression to eliminate potential confounding variables in taxonomic abundance comparisons.
Results
Sixty‐one subjects (32 PPI, 29 controls) were analysed. While no significant differences in alpha diversity were found between the PPI users and controls, a moderate shift of the PPI users away from the non‐PPI user cluster in the beta diversity was observed. After controlling for pertinent confounders, we discovered a decrease in Bacteroidetes and an increase in Firmicutes at the phylum level. We also performed species classifications and found Holdemania filiformis and Pseudoflavonifractor capillosus to be increased and decreased in the PPI cohort, respectively.
Conclusions
Long‐term PPIs use has an effect on the gut microbiome. The alteration in the ratio of Firmicutes to Bacteroidetes may pre‐dispose to the development of CDI.
Infliximab, a monoclonal antibody against tumor necrosis factor, reduces disease activity in patients with Crohn's disease. In this study of patients with fistulizing Crohn's disease who had a ...response to infliximab, continued infusions every 8 weeks were associated with a longer duration of response than were placebo infusions. After 54 weeks of treatment, 36 percent of patients in the infliximab group and 19 percent of those in the placebo group had no draining fistulas.
Maintenance treatment reduced the likelihood of relapse.
Fistulas occur in 17 to 43 percent of patients with Crohn's disease.
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,
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Perianal fistulas, the most common variant, decrease the quality of life and increase the likelihood of total colectomy.
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Although widely used in the treatment of fistulas, antibiotics, immunomodulators, and dietary therapies have not been demonstrated to result in sustained closure of fistulas in Crohn's disease.
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Surgical options are limited by the potential for compromise of anal continence. Surgical diversion of the fecal stream by a stoma often produces healing; however, many patients find a stoma to be undesirable, and the benefit of this approach is unlikely . . .
Background: It is not clear which species of bacteria may be involved in inflammatory bowel disease (IBD). One way of determining which bacteria might be likely candidates is to use ...culture-independent methods to identify microorganisms that are present in diseased tissues but not in controls. Aims: (1) To assess the diversity of microbial communities of biopsy tissue using culture-independent methods; (2) to culture the bacteria found in the tissues of patients with IBD but not in the controls; (3) to identify potential virulence factors associated with cultured bacteria. Methods: 84 biopsy specimens were collected from 15 controls, 13 patients with Crohn’s disease (CD) and 19 patients with ulcerative colitis (UC) from a population-based case–control study. Ribosomal intergenic spacer analysis (RISA) was conducted to identify unique DNA bands in tissues from patients with CD and UC that did not appear in controls. Results: RISA followed by DNA sequencing identified unique bands in biopsy specimens from patients with IBD that were classified as Escherichia coli. Targeted culture showed a significantly (p<0.05) higher number of Enterobacteriaceae in specimens from patients with IBD. The B2+D phylogenetic group, serine protease autotransporters (SPATE) and adherence factors were more likely to be associated with tissues from patients with UC and CD than with controls. Conclusions: The abundance of Enterobacteriaceae is 3–4 logs higher in tissues of patients with IBD and the B2+D phylogenetic groups are more prevalent in patients with UC and CD. The B2+D phylogenetic groups are associated with SPATE and adherence factors and may have a significant role in disease aetiology.
Linked ContentThis article is linked to Jairath et al and Jairath, Feagan papers. To view these articles visit https://doi.org/10.1111/apt.13973 and https://doi.org/10.1111/apt.14074.
Background
Previous research has assessed anxiety around colonoscopy procedures, but has not considered anxiety related to different aspects related to the colonoscopy process.
Aims
Before ...colonoscopy, we assessed anxiety about: bowel preparation, the procedure, and the anticipated results. We evaluated associations between patient characteristics and anxiety in each area.
Methods
An anonymous survey was distributed to patients immediately prior to their outpatient colonoscopy in six hospitals and two ambulatory care centers in Winnipeg, Canada. Anxiety was assessed using a visual analog scale. For each aspect, logistic regression models were used to explore associations between patient characteristics and high anxiety.
Results
A total of 1316 respondents completed the questions about anxiety (52% female, median age 56 years). Anxiety scores > 70 (high anxiety) were reported by 18% about bowel preparation, 29% about the procedure, and 28% about the procedure results. High anxiety about bowel preparation was associated with female sex, perceived unclear instructions, unfinished laxative, and no previous colonoscopies. High anxiety about the procedure was associated with female sex, no previous colonoscopies, and confusing instructions. High anxiety about the results was associated with symptoms as an indication for colonoscopy and instructions perceived as confusing.
Conclusions
Fewer people had high anxiety about preparation than about the procedure and findings of the procedure. There are unique predictors of anxiety about each colonoscopy aspect. Understanding the nuanced differences in aspects of anxiety may help to design strategies to reduce anxiety, leading to improved acceptance of the procedure, compliance with preparation instructions, and less discomfort with the procedure.
Background & Aims:
To investigate the efficacy and safety of certolizumab pegol (a polyethylene-glycolated Fab′ fragment of anti–tumor necrosis factor, CDP870) in Crohn’s disease.
Methods:
In a ...placebo-controlled, phase II study, 292 patients with moderate to severe Crohn’s disease received subcutaneous certolizumab 100, 200, or 400 mg or placebo at weeks 0, 4, and 8. The primary end point was the percentage of patients with a clinical response at week 12 (a Crohn’s Disease Activity Index decrease of ≥ 100 points or remission Crohn’s Disease Activity Index ≤ 150 points) in the intent-to-treat population.
Results:
All certolizumab doses produced significant clinical benefit over placebo at week 2 (placebo, 15.1%; certolizumab 100 mg, 29.7%
P = .033; 200 mg, 30.6%
P = .026; 400 mg, 33.3%
P = .010). At all time points, the clinical response rates were highest for certolizumab 400 mg, greatest at week 10 (certolizumab 400 mg, 52.8%; placebo, 30.1%;
P = .006) but not significant at week 12 (certolizumab 400 mg, 44.4%; placebo, 35.6%;
P = .278). Patients with baseline C-reactive protein levels of 10 mg/L or greater (n = 119) showed clearer separation between active treatment and placebo (week 12 clinical response: certolizumab 400 mg, 53.1%; placebo, 17.9%;
P = .005; post hoc analysis) owing to a lower placebo response rate than patients with C-reactive protein levels of less than 10 mg/L. Adverse events were similar among groups.
Conclusions:
Certolizumab 400 mg may be effective and is well tolerated in patients with active Crohn’s disease. High placebo response rates in the large patient subgroup with low C-reactive protein levels may have obscured statistical separation between certolizumab and placebo. Ongoing phase III trials are necessary to establish the clinical efficacy of certolizumab.
Familial adenomatous polyposis (FAP) is an autosomal dominant syndrome predisposing affected individuals to gastrointestinal (GI) cancers through a high burden of polyposis. Colorectal cancer rates ...reach 100% by the age of 45, making early colectomy a mainstay of treatment. While most patients undergo colectomy at an early age, ongoing screening and surveillance of the upper gastrointestinal tract and rectal pouch must continue throughout adulthood. Endoscopic therapy of gastric, duodenal, ampullary and rectal pouch polyps is critical to reduce morbidity and cancer related mortality. Management of these lesions is not uniform, and is dependent on their location, size, histology, and risk of malignant potential. Medical therapies targeting pathways that reduce the malignant progression of pre-cancerous lesions have been studied for many years. While studies on the use of aspirin and non-steroidal anti-inflammatories (NSAIDs) in chemoprevention have shown encouraging results in Lynch syndrome and primary colorectal cancer, the potential benefits of these medications have not been duplicated in FAP cohorts. While data remains limited on chemoprevention in FAP, a number of randomized trials are currently underway examining targeted therapies with the potential to slow the progression of the disease. This review aims to provide an in-depth review of the literature on current endoscopic options and chemopreventive therapies targeting FAP. While the endoscopic management has robust data for its use, chemoprevention in FAP is still in its infancy. The complementary use of chemopreventive agents and endoscopic therapy for FAP patients is quickly becoming a growing and exciting area of research.
The aim of this study was to assess the accuracy and utility of administrative health data in identifying persons with inflammatory bowel disease on a population basis and to determine the incidence ...and prevalence of this disease in the Canadian province of Manitoba. The data from Manitoba Health (the province's single insurer) were used to identify residents with physician and/or hospital contacts for Crohn's disease or ulcerative colitis based on International Classification of Diseases, Ninth Revision, Clinical Modification, codes between 1984 and 1995. Of 5, 182 eligible individuals, 4,514 were mailed questionnaires and 2,725 responded. Cases were defined as individuals with five or more separate medical contacts with one of these diagnoses or three or more such contacts if they were resident for less than 2 years. The accuracy of the study case definitions was high when compared with either self-report or chart review. The 1989–1994 age- and sex-adjusted annual incidence was 14.6/100, 000 for Crohn's disease and 14.3/100, 000 for ulcerative colitis. The prevalence of Crohn's disease in 1994 was 198.5/100,000, and that of ulcerative colitis was 169.7/100,000. In conclusion, the authors have successfully established and validated a population-based database of inflammatory bowel disease based on administrative data. The high incidence rates and dynamic epidemiology of inflammatory bowel disease in Manitoba indicate the presence of important environmental risk factors, which warrants further investigation. Am J Epidemiol 1999; 149:916–24.
Lysine methylation of histones in vivo occurs in three states: mono-, di- and tri-methyl. Histone H3 has been found to be di-methylated at lysine 4 (K4) in active euchromatic regions but not in ...silent heterochromatic sites. Here we show that the Saccharomyces cerevisiae Set1 protein can catalyse di- and tri-methylation of K4 and stimulate the activity of many genes. Using antibodies that discriminate between the di- and tri-methylated state of K4 we show that di-methylation occurs at both inactive and active euchromatic genes, whereas tri-methylation is present exclusively at active genes. It is therefore the presence of a tri-methylated K4 that defines an active state of gene expression. These findings establish the concept of methyl status as a determinant for gene activity and thus extend considerably the complexity of histone modifications.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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