Increase In Inflammatory Bowel Disease Research Articles

P831 Clinical factors associated with severity in patients with Inflammatory Bowel Disease in Brazil (On Behalf of GEDIIB)

Abstract Background Brazil has shown an increase in Inflammatory Bowel Disease (IBD) cases. GEDIIB (Brazilian Organization of Crohn’s Disease and Colitis) established a data platform to create a national registry of IBD patients. The study aimed to characterize the profile of IBD patients and identify clinical factors associated with IBD severity. Methods A cohort study was conducted between Jul/20 and Aug/22. Data obtained from medical records and/or directly from patients were registered via REDCap. Local institutional review boards approved the study protocol. We designed a population-based risk model aimed at stratifying severe disease based on one or more outcome variables: previous hospitalization, surgery, and biologics. Univariate and bivariate analyses and Poisson modeling were used. Results A total of 1,179 patients were included: 600 (51%) with ulcerative colitis (UC), 568 (48%) with Crohn’s Disease (CD), and 11 (0.9%) with indeterminate colitis. The mean age was 34.4±14.7y, 59% female, 73% Caucasian, and 85.3% non-smoker. Regarding the initial symptoms, 42% presented diarrhea, 38% abdominal pain, and 20% weight loss. The age of IBD symptom onset ranged from 1-87 years (32.3±14.4). According to the Montreal classification of CD, A1: 5%, A2: 63%, A3: 32%; L1: 29.7%, L2: 14.3%, L3: 41.2%, B1: 32%, B2: 26.7%, B3: 11.3%; perianal 15.5%. In UC, 46.3% presented pancolitis and 30% left-sided colitis. Only 3.9% were malnourished, 30.9% were overweight, and 18% were obese. The main extraintestinal manifestations were rheumatologic (21%). Regarding medical treatment, 68.1% of the patients received biologics (45% Infliximab, 29% Adalimumab, 9.7% Vedolizumab, and 8.8% Ustekinumab), 67% salicylates, 47.6% immunosuppressors, and 0.8% Tofacitinib. Of those submitted to surgery (34.1%, n=439), 54% were elective versus 46% urgent; most procedures (80%) were open/laparotomy, while 20% were laparoscopic. Of those, 8.5% were colectomy. The presence of CD, pancolitis, the absence of (isolated) proctitis, younger age (<20 years), rheumatologic manifestations, and no history of smoking were found to be independent risk factors. Conclusion This is the first epidemiological study using the national patient registry organized by GEDIIB. The profile of patients with severe disease is consistent with the data in the literature, characterized by younger age, greater extent of disease, and extraintestinal manifestations. Further epidemiological studies should be encouraged to guide national policies aimed at the early diagnosis and treatment of IBD.

Incidence of pediatric inflammatory bowel disease within the Vaccine Safety Datalink network and evaluation of association with rotavirus vaccination

BackgroundRecent studies have reported an increase in Inflammatory bowel disease (IBD) incidence in young children, highlighting the need to better understand risk factors for the development of IBD. Licensed for use in infants in 2006, the oral, live-attenuated rotavirus vaccine has biologic plausibility for instigating inflammation of the gut mucosa as a pathway to immune dysregulation. MethodsOver a ten-year period, we evaluated incidence of IBD within a cohort of children under the age of ten, enrolled in seven integrated healthcare delivery systems. We conducted a nested case-control study to evaluate the association between rotavirus vaccination and IBD using conditional logistic regression. Cases were confirmed via medical record review and matched to non-IBD controls on date of birth, sex, and study site. ResultsAmong 2.4 million children under the age of 10 years, 333 cases of IBD were identified with onset between 2007 and 2016. The crude incidence of IBD increased slightly over the study period (p-value for trend = 0.046). Of the 333 cases, 227 (68%) were born prior to 2007. Forty-two cases born in 2007 or later, with continuous enrollment since birth were included in the case-control study and matched to 210 controls. The adjusted odds ratio for any rotavirus vaccination in IBD cases, compared to matched controls, was 0.72 (95% confidence interval 0.19–2.65). ConclusionsData from this large pediatric cohort demonstrate a small overall increase in IBD incidence in young children over a ten-year period. The data suggest that rotavirus vaccination is not associated with development of IBD.

A summary of feed additives, intestinal health and intestinal alkaline phosphatase in piglet nutrition

Weaning is considered the “critical window” in the piglet’s life because it is associated with several stress factors, such as loss of contact with the mother and original litter, solid diet, environmental and structural changes, and the establishment of a new hierarchy. During this abrupt period, several events such as reduced feed intake, high morbidity, susceptibility to enteric infections and post-weaning diarrhoea are observed. The nutritional landscape of the piglet gut is modified, which can compromise the maturity of the gastrointestinal system, the stable intestinal microbiome and the active immunity developed as an indicator of intestinal health. However, with increased awareness of feed safety issues and the development of drug-resistant bacteria, the interest in producing pigs without the use of antimicrobial growth promoters (AGP) is increasing, since long-term use and therapeutic doses of AGP can contribute to the reduction of bacterial diversity and increase of inflammatory bowel disease (IBD). Thus, the most widely researched alternatives include the use of feed additives, feeding strategies, nutraceuticals/functional foods and available handling that can reduce the risk of IBD beyond basic nutritional functions. Studies have reported intestinal alkaline phosphatase as a new nutritional therapy associated with intestinal health which may be a “key additive” in the AGP replacement. In this review article, the purpose is to show some current aspects of feed additive research, addressing a concept of the “intestinal health” from different points of view and properties of alkaline phosphatase.

Young mice expel the tapeworm Hymenolepis diminuta and are protected from colitis by triggering a memory response with worm antigen.

Infection with helminth parasites reduces the severity of concomitant inflammatory disease in adult mice. There is an alarming increase of inflammatory bowel disease (IBD) in children. It is important to determine whether helminth therapy would be of value in pediatric IBD and whether triggering immunological memory to the worm would be anticolitic. Three-week-old (young) and eight-week-old (adult) Balb/c mice were infected with H. diminuta, and infectivity and T helper 2 (Th2) immunity were assessed. Other mice received H. diminuta with or without a crude worm extract ( HdE) 28-42 days postinfection (dpi) with or without dinitrobenzene sulphonic acid [DNBS, 1.5 mg (young) or 3 mg (adults), ir], and colitis was assessed 72 h later. Infected young mice developed Th2 immunity and expelled H. diminuta; expulsion was delayed by ~2 days compared with adult mice. Colitis, as gauged by macroscopic disease and histopathology scores, was less severe in young mice infected 10 days, but not 8 days, before DNBS. Protection against DNBS-induced colitis was accompanied by an increased capacity to make interleukin (IL)-4 and IL-10. Mice infected with H. diminuta were not protected from DNBS-colitis when challenged 28 days later; however, injection of these mice with HdE coincident with DNBS resulted in less disease and increased splenic IL-4 and IL-10. Using a boost (500 μg HdE, 28 dpi) and repeat HdE (100 μg, 42 dpi) regimen with infected mice suppressed DNBS-colitis, as did adoptive transfer of splenic CD4+ T cells from infected mice with low-dose HdE challenge. Should these data translate to IBD, then helminth therapy could be of value in pediatric-onset IBD, and defining the antigen(s) that elicit antihelminth immunological memory could serve as an anticolitic approach in previously infected individuals. NEW & NOTEWORTHY This study demonstrates that juvenile mice are protected from colitis by infection with the tapeworm Hymenolepis diminuta and that using worm antigen to trigger an immunological memory response in previously infected mice can be used to limit the severity of colitis.

Understanding and Preventing the Global Increase of Inflammatory Bowel Disease

The inflammatory bowel diseases (IBDs) are contemporary conditions of industrialized societies. The prevalence of IBD continues to increase steadily in Western countries, and newly industrialized countries have a rapidly increasing incidence. The global spread of IBD appears to associate with Westernization of diets and environments, which affects the intestinal microbiome and increases the risk of IBD in genetically susceptible individuals. It is important to increase our understanding of these events to slow progression of IBD. We present a long-term plan to develop interventions that slow or stop the global increase in the incidence of IBD.

Does Inflammatory Bowel Disease Increase the Risk of Malignancies in Patients with Primary Sclerosing Cholangitis: A Systematic Review and Meta-Analysis

Does Inflammatory Bowel Disease Increase the Risk of Malignancies in Patients with Primary Sclerosing Cholangitis: A Systematic Review and Meta-Analysis

A SURVEY OF DISEASES IN CAPTIVE RED WOLVES (CANIS RUFUS), 1997-2012.

Conservation efforts to preserve the red wolf (Canis rufus) have been in progress since the 1970s through the U.S. Fish and Wildlife Service Red Wolf Recovery Program and the Association of Zoos and Aquarium's Red Wolf Species Survival Plan. An ongoing part of this project has been to monitor mortality trends, particularly to look for potential genetic conditions resulting from inbreeding given the small founding population of only 14 individuals. An initial survey was conducted in the 1990s but a comprehensive assessment of the population has not been done since then. This retrospective review evaluates mortality in the population from 1997 to 2012 through analysis of gross necropsy and histology records provided by cooperating institutions that housed red wolves during the time period of interest. Of the 378 red wolves that died during this 15-yr period, 259 animals had gross necropsy records, histology records, or both that were evaluated. The major causes of neonatal death were parental trauma, stillbirth, or pneumonia. Overall, juveniles had very low mortality rates with only 12 wolves aged 30 days to 6 mo dying during the study period. The most common cause of death within the adult populations was neoplasia, with epithelial neoplasms, carcinomas, and adenocarcinomas being the most common types reported. Gastrointestinal disease was the second most common cause of death, particularly gastric dilation and volvulus, inflammatory bowel disease, and gastrointestinal perforations. These findings are in stark contrast to causes of mortality in the wild population, which are primarily due to human-related activities such as vehicular trauma, gunshot, or poisoning. Overall, the captive population has few health problems, but an increase in inflammatory bowel disease in particular warrants further investigation.

Dietary emulsifiers impact the mouse gut microbiota promoting colitis and metabolic syndrome.

SummaryThe intestinal tract is inhabited by a large diverse community of microbes collectively referred to as gut microbiota. While gut microbiota provide important benefits to its host, especially in metabolism and immune development, disturbance of the microbiota-host relationship is associated with numerous chronic inflammatory diseases, including inflammatory bowel disease (IBD) and the group of obesity-associated diseases collectively referred to as metabolic syndrome. A primary means by which the intestine is protected from its microbiota is via multilayered mucus structures that cover the intestinal surface thus allowing the vast majority of gut bacteria to be kept at a safe distance from epithelial cells that line the intestine 1. Thus, agents that disrupt mucus-bacterial interactions might have the potential to promote diseases associated with gut inflammation. Consequently, it has been hypothesized that emulsifiers, detergent-like molecules that are a ubiquitous component of processed foods and that can increase bacterial translocation across epithelia in vitro 2, might be promoting the post-mid 20th century increase in IBD 3. Herein, we observed that, in mice, relatively low concentrations of two commonly used emulsifiers, namely carboxymethylcellulose and polysorbate-80, induced low-grade inflammation and obesity/metabolic syndrome in WT hosts and promoted robust colitis in mice predisposed to this disorder. Emulsifier-induced metabolic syndrome was associated with microbiota encroachment, altered species composition, and increased pro-inflammatory potential. Use of germ-free mice and fecal transplants indicated that such changes in microbiota were necessary and sufficient for both low-grade inflammation and metabolic syndrome. These results support the emerging concept that perturbed host-microbiota interactions resulting in low-grade inflammation can promote adiposity and its associated metabolic effects. Moreover, they suggest that broad use of emulsifying agents might be contributing to increased societal incidence of obesity/metabolic syndrome and other chronic inflammatory diseases.

May artificial sweeteners not sugar be the culprit of dramatic increase of inflammatory bowel disease in China?

May artificial sweeteners not sugar be the culprit of dramatic increase of inflammatory bowel disease in China?

When and How Was the New Round of Increase in Inflammatory Bowel Disease in the United States Started?

When and How Was the New Round of Increase in Inflammatory Bowel Disease in the United States Started?

Fat, bile and gut microbes

Western-style diets could be contributing to the rapid increase in inflammatory bowel disease. New research suggests that dietary fat can alter bile composition and so favour the growth of pro-inflammatory gut microbes. See Letter p.104 Milk fat is shown here to potentiate experimental colitis in susceptible mice, in association with increased luminal concentrations of sulphite-reducing bacteria. Mice fed a diet with comparable caloric intake containing unsaturated fatty acids are protected. The inflammation is caused by milk-fat-promoted taurine conjugation with bile acids, which increases the availability of organic sulphur used by the bacteria. This finding supports the suggestion that the recent upwards trend in complex immune disorders such as inflammatory bowel diseases could reflect changes in human microbiomes elicited in genetically susceptible individuals by dietary and other environmental changes.

What caused the recent worldwide increase of inflammatory bowel disease: Should sucralose be added as a suspect?

Despiteextensive research, the cause of IBDremains unknown.About a decade ago a series ofaccidental findings led me to suspectthat the impaired inactivation of diges-tive protease and the resulting acceler-ated degradation of the mucus layerand underlying endothelium due to theinhibition of gut bacteria by dietarychemicals like saccharin may haveplayed a causative role in IBD.

Population‐based cases control study of inflammatory bowel disease risk factors

The rapid increase in inflammatory bowel disease (IBD) incidence confirms the importance of environment in its etiology. We aimed to assess the role of childhood and other environmental risk factors in IBD. A population-based case-control study was carried out in Canterbury, New Zealand. Participants comprised 638 prevalent Crohn's disease (CD) cases, 653 prevalent ulcerative colitis (UC) cases and 600 randomly-selected sex and age matched controls. Exposure rates to environmental risk factors were compared. Unadjusted and adjusted odds ratios (OR) with 95% confidence intervals (CI) are presented. A family history of IBD (CD OR 3.06 [2.18-4.30], UC OR 2.52 [1.90-3.54]), cigarette smoking at diagnosis (CD OR 1.99 [1.48-2.68], UC OR 0.67 [0.48-0.94]), high social class at birth (CD and UC trend, P < 0.001) and Caucasian ethnicity (CD OR 2.04 [1.05-4.38], UC OR 1.47 [1.01-2.14]) were significantly associated with IBD. City living was associated with CD (P < 0.01). Being a migrant was associated with UC (UC OR 1.40 [1.14-2.01]). Having a childhood vegetable garden was protective against IBD (CD OR 0.52 [0.36-0.76], UC OR 0.65 [0.45-0.94]) as was having been breast-fed (CD OR 0.55 [0.41-0.74], UC OR 0.71 [0.52-0.96]) with a duration-response effect. Appendicectomy, tonsillectomy, infectious mononucleosis and asthma were more common in CD patients than controls (P < 0.01). The importance of childhood factors in the development of IBD is confirmed. The duration-response protective association between breast-feeding and subsequent development of IBD requires further evaluation, as does the protective effect associated with a childhood vegetable garden.