High Incidence Of Inflammatory Bowel Disease Research Articles

Childhood and adolescent residential and farm pesticide exposures and inflammatory bowel disease incidence in a U.S. cohort of women

Background and aimsThere are few known risk factors for inflammatory bowel disease (IBD), an autoimmune disease characterized by chronic intestinal inflammation. Use of specific pesticides has been associated with higher incidence of IBD among pesticide applicators and their spouses, but no study has examined pesticide exposure in early life, a period where the human immune system undergoes rapid changes. We evaluated pesticide use during childhood and adolescence and incidence of IBD among US women enrolled in the Sister Study. MethodsIncident IBD diagnoses between enrollment (2003–2009) and 2021 were identified and validated with medication use and colectomy/colostomy surgery. We estimated hazard ratios (HR) and 95 % confidence intervals (CI) for the relationship of childhood/adolescent residential and farm pesticide exposures with IBD incidence using Cox models, accounting for age, race and ethnicity, education, smoking, and birth year. ResultsWe identified 277 incident IBD cases among 48,382 eligible participants. IBD hazard was elevated among those whose childhood residence was regularly treated with pesticides, especially among those who ever personally applied pesticides (HR = 1.39, 95%CI: 0.65, 2.99). We observed a positive association between IBD and exposure to broadcast pesticide sprays before DDT was banned (>6 times vs. never HR = 1.56, 95%CI: 1.06, 2.31). Among participants who lived on a farm during childhood/adolescence for ≥1 year (N = 9162), IBD hazards were higher among those who were in crop fields during pesticide application (HR = 2.06, 95%CI: 0.94, 4.51) and who ever personally applied pesticides on crops (HR = 1.85, 95%CI: 0.81, 4.18) or livestock (HR = 2.58, 95%CI: 1.14, 5.83). ConclusionEarly-life pesticide exposure may be a novel risk factor for IBD. Practices that reduce pesticide exposure during early life may help reduce the burden of this disease.

Dietary Exposures and Interventions in Inflammatory Bowel Disease: Current Evidence and Emerging Concepts.

Diet is intimately linked to the gastrointestinal (GI) tract and has potent effects on intestinal immune homeostasis. Inflammatory bowel disease (IBD) is characterized by chronic inflammation of the GI tract. The therapeutic implications of diet in patients with IBD have received significant attention in recent years. In this review, we provide a contemporary and comprehensive overview of dietary exposures and interventions in IBD. Epidemiological studies suggest that ultra-processed foods, food additives, and emulsifiers are associated with a higher incidence of IBD. Exclusion and elimination diets are associated with improved symptoms in patients with IBD, but no effects on objective markers of inflammation. Specific dietary interventions (e.g., Mediterranean, specific carbohydrate, high fiber, ketogenic, anti-inflammatory diets) have been shown to reduce symptoms, improve inflammatory biomarkers, and quality of life metrics to varying degrees, but these studies are limited by study design, underpowering, heterogeneity, and confounding. To date, there is no robust evidence that any dietary intervention alone may replace standard therapies in patients with IBD. However, diet may play an adjunct role to induce or maintain clinical remission with standard IBD therapies. The results of novel dietary trials in IBD such as personalized fiber, intermittent fasting, and time-restricted diets are eagerly awaited.

The epidemiology of inflammatory bowel disease: Clues to pathogenesis?

Historically, inflammatory bowel disease (IBD) was most common in North America and Europe and more common with a north-south gradient. Over the past century, there has been a marked increase in IBD in general and in childhood IBD in particular and over the past 50 years IBD has spread into the developing world. The greatest risk factor of developing IBD is an affected family member. Concordance rates between dizygotic twins is ∼4% and ∼50% in monozygotic twins, and more than half of pairs are diagnosed within 2 years of each other. Nevertheless, most patients with IBD do not have an affected family member. More than 200 genes are associated with an increased risk for IBD, but most associations are weak with odds ratios between 1.2 and 2.0 suggesting the environment plays a role. IBD is more common in urban than rural regions and is associated with "good standards" of domestic hygiene during childhood. People who migrate from areas with a low incidence to areas with a high incidence of IBD have an increased risk of developing IBD and the younger they are when they migrate, the greater their risk of developing IBD. Moreover, people who migrate from regions with a high incidence to areas with a low incidence of IBD have a decreased risk of developing IBD. Together, these findings strongly suggest particular environmental exposures occurring early in life may trigger inflammatory bowel disease in genetically susceptible individuals. The key is figuring out what those exposures might be.

The causal relationship between psoriasis, psoriatic arthritis, and inflammatory bowel diseases

Psoriasis is more common in patients with inflammatory bowel disease (IBD) than in the general population. Similarly, patients with psoriasis or psoriatic arthritis (PsA) have a higher incidence of IBD. However, whether this association is causal remains unknown. Therefore, we used a two-sample bidirectional Mendelian randomization (MR) analysis to identify this relationship. According to MR analysis, psoriasis and PsA causally increased the odds of developing Crohn’s disease (OR = 1.350 (1.066–1.709) P = 0.013; OR = 1.319 (1.166–1.492) P < 0.001). In contrast, MR estimates gave little support to a possible causal effect of psoriasis, PsA, on ulcerative colitis (OR = 1.101 (0.905–1.340) P = 0.335; OR = 1.007 (0.941–1.078) P = 0.831). Similarly, the reverse analysis suggested the Crohn’s disease causally increased the odds of psoriasis and PsA (OR = 1.425 (1.174–1.731) P < 0.001; OR = 1.448 (1.156–1.182) P = 0.001), whereas there are no causal association between ulcerative colitis and psoriasis, PsA (OR = 1.192 (0.921–1.542) P = 0.182; OR = 1.166 (0.818–1.664) P = 0.396). In summary, our MR analysis strengthens the evidence for the bidirectional dual causality between psoriasis (including PsA) and Crohn’s disease.

Diets for inflammatory bowel disease: What do we know so far?

In recent years, the role of diet in the pathogenesis of inflammatory bowel disease (IBD) has gained great interest within the scientific community. Eating habits from industrialised countries (the so-called western diet or WD) have been associated with a higher incidence of IBD in observational studies, although the dietary factors responsible for the development of the disease are still to be elucidated. Some components of the diet with proinflammatory potential may cause changes in immunity and intestinal microbiota, leading to the inflammatory reaction that causes IBD-related lesions. The quality of available evidence is low, due to methodological issues, such as the lack of intervention studies, small sample size and heterogeneity of studies. For this reason, scientific societies have offered their recommendations using clinical practice guidelines and consensus documents, in order to establish a common criterion in the nutritional treatment of patients with IBD. The objective of this review was to summarise the data published regarding diet in IBD and review the recommendations given by scientific societies.

Radon exposure and inflammatory bowel disease in a radon prone area.

inflammatory bowel disease (IBD) is a multifactorial pathology with an increasing incidence. There is no study that has assessed a possible relationship with very high residential radon exposure in the study area. The aim of the study was to analyze if residential radon concentration is associated with a higher incidence of IBD. an ecological study was performed. All incident cases of inflammatory bowel disease in the area of Santiago de Compostela were included between January and December 2017. Radon levels at a municipal level were correlated with demographic factors and type of IBD. ninety-six patients were included, 63 (65.6 %) with ulcerative colitis, 29 (30.25) with Crohn's disease and four (4.2 %) with indeterminate colitis. The incidence rate per 100,000 inhabitants-year was 21.6 cases. There were no statistically significant differences in the type of disease developed regarding radon levels (p > 0.05). No correlation between radon levels and the cumulative incidence of inflammatory bowel disease at the municipal level was observed (Spearman's rho = 0.13, p-value 0.5). in the area of Santiago de Compostela, there is a higher incidence of IBD in comparison with previous studies using western countries as reference. However, there was no correlation with the municipal average radon concentration and incidence of IBD or any of its types in this study.

Inflammatory Bowel Diseases and Irritable Bowel Syndrome: Overlap of Two Nosological Forms or Two Variants of the Same Disease?

Aim. To review available literature data on the relationship between inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS).Key findings. Current publications on IBD and IBS present different viewpoints on their relationship. Thus, researchers have noted a high incidence of IBD against the background of IBS, frequent persistence of IBS-like symptoms after achieving IBD remission, as well as the possibility of overlapping the diseases. According to literature data, IBD and IBS should be treated as different forms of the same disease. An opinion is expressed that IBS-like complaints in patients with IBD remission should be considered as a separate disease referred to as “irritated inflammatory intestinal syndrome”. Treatment of IBS-like symptoms in patients with IBD remission has thus far not been developed.Conclusion. The problem of the relationship between IBD and IBS is currently controversial, thus requiring further clarification.

Genomic architecture of inflammatory bowel disease in five families with multiple affected individuals.

Currently, the best clinical predictor for inflammatory bowel disease (IBD) is family history. Over 163 sequence variants have been associated with IBD in genome-wide association studies, but they have weak effects and explain only a fraction of the observed heritability. It is expected that additional variants contribute to the genomic architecture of IBD, possibly including rare variants with effect sizes larger than the identified common variants. Here we applied a family study design and sequenced 38 individuals from five families, under the hypothesis that families with multiple IBD-affected individuals harbor one or more risk variants that (i) are shared among affected family members, (ii) are rare and (iii) have substantial effect on disease development. Our analysis revealed not only novel candidate risk variants but also high polygenic risk scores for common known risk variants in four out of the five families. Functional analysis of our top novel variant in the remaining family, a rare missense mutation in the ubiquitin ligase TRIM11, suggests that it leads to increased nuclear factor of kappa light chain enhancer in B-cells (NF-κB) signaling. We conclude that an accumulation of common weak-effect variants accounts for the high incidence of IBD in most, but not all families we analyzed and that a family study design can identify novel rare variants conferring risk for IBD with potentially large effect size, such as the TRIM11 p.H414Y mutation.

Ulcerative Colitis – What Can We Learn from the Asia-Pacific Region?

A recent epidemiological study clearly demonstrated that inflammatory bowel disease (IBD), especially ulcerative colitis, is a rapidly emerging disease in the Asia Pacific region (1). A systematic review of the global incidence and prevalence of IBD before publication of the Asia Pacific data (2) confirmed the worldwide nature of IBD. In time-trend analyses, it showed that 75% of Crohn disease studies and 60% of ulcerative colitis studies reported statistically significant increases in incidence (2). The emergence of IBD in the Asia Pacific region suggests strong environmental influence on the pathogenesis of IBD including socioeconomic, lifestyle and dietary changes. The age-standardized incidence of ulcerative colitis in the Asia Pacific region ranged from 0.24 to 7.47 per 100,000 population, with the lowest incidence in Bangkok and the highest in Australia. Even highly westernized Asian countries, such as Hong Kong, have an ulcerative colitis incidence of 1.30 per 100,000 population (1). The incidence of Crohn disease in Australia was nearly double that of ulcerative colitis; however, in the Asian countries, ulcerative colitis was generally more prevalent than Crohn disease. In a recent Asia Pacific epidemiology study of IBD incidence (1), the distribution of ulcerative colitis location in Australia and in Asia were similar, with approximately one-third each being proctitis, left-sided colitis, and extensive or total colitis (1). The Asia Pacific epidemiology study did not include South Korea, Japan or India, which tend to have a higher incidence of IBD than other Asian countries. However, in the current issue of the Journal, Park et al (3) (pages 125 to 130) reported a retrospective analysis of disease location at diagnosis in 240 ulcerative colitis patients diagnosed at Asan Medical Centre, Seoul, South Korea. Approximately 19% of patients had an atypical distribution of disease, including patchy or skip lesions or, less commonly, rectal sparing. Such atypical distribution was more common in patients reported to demonstrate appendiceal orifice inflammation. Skip lesions were more common in the proximal colon. While such atypical distribution inevitably raises the question of Crohn’s colitis, 67% of ulcerative colitis patients showing atypical distribution at diagnosis had reverted to the typical distribution of lesions at follow-up colonoscopy. The ulcerative colitis disease course and outcome of individuals with atypical disease location was similar to those with more classical disease location. While such atypical distribution of ulcerative colitis has been sporadically reported in the West (4,5), including 27% of ulcerative colitis patients showing discontinuous inflammation of the appendiceal orifice in a prospective study, rectal sparing is considered to be unusual in the West after meticulous pathological examination of colectomy specimens (6). This is not surprising given that in the study by Park et al (3), follow-up colonoscopy showed that the distribution of ulcerative colitis had reverted to the classical in the majority of patients. However, several reports from Asia, especially Japan, Korea and India, with higher incidence of ulcerative colitis in Asia, have reported atypical distribution of ulcerative colitis (7–9) despite the contrary data in the recent Asia Pacific epidemiology study. Although single-centre and retrospective, the study by Park et al (3) substantiates these previous findings. It is important to recognize that the Asia Pacific region is a vast, inhomogeneous area with multiple cultures, lifestyles, environment, diet and genetics. For example, three regions of mainland China had ulcerative colitis incidences of 2.05, 0.42 and 0.41 per 100,000 population (1), suggesting unique environmental influences in specific regions. The study by Park et al (3) and previous studies encourage us to obtain additional epidemiological and environmental data collected prospectively from geographical regions with emerging IBD. It will be important to understand whether disease presentation varies in different geographical areas based on colonic microbiome, dietary habits and genetics. This may shed light on its pathogenesis and provide more evidence to answer the question whether ulcerative colitis is ‘one disease or many’. This discussion may be even more relevant in the case of Crohn disease. It especially points to the challenges of epidemiological studies that attempt to distinguish between ulcerative colitis and Crohn’s colitis.

Changing Incidence of Inflammatory Bowel Disease: Environmental Influences and Lessons Learnt from the South Asian Population

Inflammatory bowel disease (IBD) is a chronic relapsing inflammatory disorder of the gastrointestinal tract associated with significant morbidity. While IBD occurs in genetically susceptible individuals, the etiology is multifactorial, involving environmental influences, intestinal dysbiosis, and altered immune responses. The rising incidence of IBD in industrialized countries and the emergence of IBD in countries with traditionally low prevalence underscore the importance of environmental influences in the pathobiology of the disease. Moreover the high incidence of IBD observed in the South Asian immigrant population in the United Kingdom and Canada further supports the influence of environmental factors.

Gut bacterial profile in patients newly diagnosed with treatment-na&amp;iuml;ve Crohn&amp;#39;s disease

Objectives:The aim of this study was to define the composition of the gut bacterial flora in Norwegian patients with early stage Crohn’s disease (CD).Methods:By using a nonselective metagenomics approach, the general bacterial composition in mucosal biopsies from the ileum and the colon of five subjects, four patients with different phenotypes of CD, and one noninflammatory bowel disease control, was characterized. After partial 16S ribosomal RNA (rRNA) gene sequencing, BLAST homology searches for species identification and phylogenetic analysis were performed.Results:An overall biodiversity of 106 different bacterial operational taxonomic units (OTUs) was detected in the cloned libraries. Nearly all OTUs belonged to the phylae Bacteroidetes (42% in CD, 71% in the control) or Firmicutes (42% in CD, 28% in the control), except for some OTUs that belonged to the phylum Proteobacteria (15% in CD, 0% in the control) and a few OTUs that could not be assigned to a phylum (2% in CD, 1% in the control).Conclusion:Based on the high incidence of inflammatory bowel disease (IBD) in Norway, this pilot study represents a relevant determination of the gut microbiota in Norwegian patients compared to previous findings in other countries. The bacterial profile of Norwegian CD patients was found to be similar to that of CD patients in other countries. The findings do not support a particular bacterial composition as a predominant causative factor for the high incidence of IBD that exists in some countries.

What Made Canada Become a Country with the Highest Incidence of Inflammatory Bowel Disease: Could Sucralose be the Culprit?

Inflammatory bowel disease (IBD) (which includes both ulcerative colitis and Crohn’s disease [CD]) emerged and dramatically increased in the past century (1). Early studies revealed that IBD was most prevalent in countries such as the United Kingdom, the United States and those in northern Europe (1). Compared with these countries, the prevalence of IBD in Canada was much lower. This was demonstrated in early epidemiological studies conducted in Canada. According to a review by Mayberry and Rhodes (2), a study published in 1972 reported the incidence and prevalence of CD in Sherbrooke, Quebec, at only 0.7 and 6.3 per 100,000 population, respectively, which were much lower than countries such as the United Kingdom, the United States, Sweden, Denmark, and even Israel and New Zealand at the same time or even decades earlier. However, studies in recent years have suddenly found that Canada has become a country with the highest incidence of IBD (3). For example, the prevalence of CD in Alberta in 1981 was only 44 per 100,000 population (4), compared with 91 per 100,000 in Olmsted County, Minnesota (USA) on January 1, 1980 (5). However, the prevalence of CD in Alberta increased to 283 per 100,000 on July 1, 2000 (3), compared with 174 per 100,000 in Olmsted County in January 1, 2001 (6). It would be valuable to know what caused the dramatic increase of IBD in Canada because it may provide critical information regarding its etiology. A decade ago, a series of accidental findings made me suspect that the impaired inactivation of digestive proteases due to the inhibition of gut bacteria by dietary chemicals, such as saccharin, play a causative role in IBD as a result of the accelerated degradation of the mucous layer and underlying endothelium (7). It provided an explanation for many puzzles in IBD such as the dramatic increase of IBD in the 1950s and 1960s, and its levelling off since the latter part of the 1970s, as observed in many western countries including Canada (4,7). However, this hypothesis was challenged by the failure to provide an explanation for the recent high incidence of IBD in Canada, which had adopted more stringent standards for the use of saccharin than most other western countries after the finding of carcinogenic effects of saccharin on the bladders of experimental animals in 1977. If not saccharin, then what caused the remarkable increase of IBD in Canada? I suggest that sucralose may be the culprit. Sucralose is a new, non-nutrient, high-intensity sweetener that has many superior properties. It is approximately 600 times sweeter than sucrose (thus two times sweeter than saccharin). Similar to saccharin, sucralose is heat and pH stable, but without the bitter aftertaste (8). In 1991, Canada was the first country to approve the use of sucralose, and it was allowed to be used as a tabletop sweetener in breakfast cereals, beverages, desserts, toppings, fillings, chewing gum, breath mints, fruit spreads, salad dressings, confectionary, bakery products, processed fruits and vegetables, alcoholic beverages, puddings and table syrups (8). Interestingly, the study by Wrobel et al (9) reported that the incidence of pediatric IBD in Southern Alberta was 2.3 (per 100,000 population) between 1983 and 1987, 2.5 between 1988 and 1992, 5.0 between 1993 and 1998, and 6.5 between 1999 and 2005 (9), indicating a dramatic increase in the early 1990s. Could sucralose cause the increase of IBD in Canada? How? Similar to saccharin, sucralose can also exert potent inhibition of gut bacteria (10). However, it may have a more pronounced effect on gut bacteria than saccharin in that approximately 65% to 95% of sucralose is excreted through the feces unchanged (10), while a large proportion of saccharin is absorbed and eliminated through urine; the acceptable daily intake of sucralose is 15 mg/kg, but only 5 mg/kg for saccharin. As I suggested a decade ago, regarding the possible risk of saccharin on IBD (7), sucralose may have a similar but stronger impact on gut bacteria, digestive protease inactivation and gut barrier function. This may provide a possible explanation for the more pronounced high incidence of IBD observed in Canada. The use of sucralose is soaring, and is now being used in thousands of food products (10). Therefore, it would be worthwhile to investigate whether possible links between sucralose intake and IBD exist, before it is too late.

Incidence of Inflammatory Bowel Disease in Children in Southeastern Norway: A Prospective Population-based Study 1990-94

Background: Most incidence studies of ulcerative colitis (UC) and Crohn disease (CD) have dealt with adults and there are have been few population-based prospective studies of the incidence of inflammatory bowel disease (IBD) in children. The aim of this study was to determine the incidence after re-evaluation of the diagnosis of UC and CD in childhood and adolescence in a prospective population-based survey. Methods: From 1 January 1990 to 31 December 1993, all newly diagnosed patients with UC and CD under the age of 16 years were registered. On 1 January 1992 there were 174,482 children in the study population. The diagnosis was based on internationally accepted criteria and all clinical data were reviewed by two gastroenterologists independently of each other. All patients were subjected to a second evaluation 1 year after inclusion in the study. Patients initially diagnosed as indeterminate colitis (IND) were also reassessed. Results: A total of 14 cases of UC, 13 cases of CD and 2 cases of IND were registered during the study period. At re-evaluation of the two patients diagnosed as IND, one was reclassified as having UC and one as having CD. This yielded a mean annual incidence of 2.14 (95% CI 1.20-3.54) per 100,000 for UC and 2.00 (95% CI 1.10-3.36) per 100,000 for CD. The male:female ratio in UC was 4.0 and 1.8 in CD. Median time interval from onset of symptoms to diagnosis was 4 months for UC and 5 months for CD. A high proportion of the children with UC (80%; 12/15) had extensive colitis. Four patients with CD had a first-degree relative with IBD. Conclusion: This study does not support an increased incidence of paediatric CD over the past decade. The incidence of paediatric UC seems to have remained stable over the past 30 years. In the CD group, we find a high incidence of IBD in first-degree relatives.

Small-area variations and sociodemographic correlates for the incidence of Crohn's disease and ulcerative colitis.

The objectives of this study were to describe variations in the incidence of inflammatory bowel disease (IBD) within the Canadian province of Manitoba and to analyze sociodemographic factors associated with these variations. The authors used the Manitoba Health insurance databases to measure incidence rates of Crohn's disease and ulcerative colitis for each of 52 postal areas in Manitoba, in 1987-1996. The sociodemographic characteristics of the postal areas were based on data from the 1996 Canadian census. The overall incidence rates of Crohn's disease and ulcerative colitis were identical-15.6 per 100,000. Both diseases showed substantial geographic variation, with incidence rates differing significantly from the provincial average in 15 postal areas for Crohn's disease and in 13 postal areas for ulcerative colitis. There was a significant geographic correlation in the incidence of Crohn's disease and ulcerative colitis (r = 0.49, p < 0.001). The incidence of IBD was higher in urban areas (incidence rate ratio (IRR) = 1.21, 95% confidence interval (CI): 1.00, 1.45). Aboriginal Canadians had significantly lower rates of both Crohn's disease (IRR = 0.11, 95% CI: 0.05, 0.22) and ulcerative colitis (IRR = 0.57, 95% CI: 0.42, 0.79). A higher incidence of IBD was ecologically associated with a higher average family income, a lower proportion of immigrant and Aboriginal Canadian populations, and a smaller average family size.

Novel intestinal Helicobacter species isolated from cotton-top tamarins (Saguinus oedipus) with chronic colitis.

A disease similar to ulcerative colitis in humans has been identified in cotton-top tamarins (CTTs) in captivity. The clinical signs include weight loss, diarrhea, and rectal bleeding with the pathological features and biochemical abnormalities of ulcerative colitis. Approximately 25 to 40% of these animals develop colon cancer after 2 to 5 years of captivity. An infectious etiology has been proposed; however, no microbial agent to date has been identified. Helicobacter spp. have been associated with enterocolitis and inflammatory bowel disease (IBD) in humans and animals. Infection with Helicobacter pylori or Helicobacter mustelae is associated with an increased risk of gastric adenocarcinoma and lymphoma of the mucosa-associated lymphoid tissue. Helicobacter hepaticus causes hepatitis, hepatic adenomas, and hepatocellular carcinomas in susceptible strains of mice. The aim of this study was to assess a colony of CTTs with a high incidence of IBD and colon cancer for the presence of colonic Helicobacter spp. A fusiform, gram-negative bacterium with bipolar flagella and periplasmic fibers was isolated from the feces of CTTs. The bacterium grew under microaerobic conditions at 37 and 42 degrees C but not at 25 degrees C, did not hydrolyze urea, was positive for catalase and oxidase, did not reduce nitrate to nitrite, did not hydrolyze indoxyl acetate or alkaline phosphatase, and was resistant to nalidixic acid, cephalothin, and trimethoprim-sulfamethoxazole. On the basis of 16S rRNA gene sequence analysis, the organism was classified as a novel Helicobacter species. This is the first Helicobacter isolated from CTTs. Further studies are needed to elucidate the role of this novel Helicobacter sp. in the pathogenesis of ulcerative colitis and colonic adenocarcinoma in CTTs.