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Restorative proctocolectomy with ileal pouch-anal anastomosis is the surgical treatment of choice for patients with medically-refractory ulcerative colitis (UC) and familial adenomatous polyposis (FAP). Whilst quality of life is generally good, as many as 83% of patients associate dietary factors with the onset of symptoms(1) and around two-thirds employ some form of dietary restriction post-pouch creation(2,3). There is growing interest to understand the role of diet (as a whole) on pouch function and how it can be used therapeutically. It is imperative that we know the dietary characteristics of pouch patients before attempting to introduce strategies altering their food choice. Since there is good rationale to assess overall diet quality to identify potential avenues for targeting dietary strategies, this study aimed to examine the frequency of perceived food intolerances and diet quality in patients with an ileoanal pouch and the relationship between these two indices. In this cross-sectional study, patients with an ileoanal pouch completed a food intolerance questionnaire and a validated 297-item semi-quantitative food frequency questionnaire (Monash Comprehensive Nutritional Assessment Questionnaire). Dietary data was used to score diet quality using the 2013 Dietary Guidelines Index (DGI), a scoring system which compares how closely an individual’s dietary intake aligns with the Australian Dietary Guidelines (ADG). The DGI also comprises of 11 subcomponents (scored out of 10 respectively) based on each of the ADG guidelines and provides a total score of 110, with higher scores reflecting greater compliance to the ADG. In order to determine if perceived dietary intolerances was negatively associated with the intake of specific dietary factors, univariable and multivariable linear regression analysis of the correlation of intolerance and diet quality was performed. Of the 58 (10 FAP and 48 UC) patients studied, 81% of UC and 80% of FAP patients reported dietary intolerances. Mean total DGI score was 78 (95% CI: 74-80) of 110 in the overall pouch cohort with no differences across pouch sub-groups. However, only 5% of patients achieved a full score for food variety. Both uni- [OR −0.94 (−1.7,-0.10); p = 0.02] and multivariable analysis (adjusting for age and sex) showed that only intolerances to dairy products were associated with reduced intake of lactose-containing dairy [OR −0.29 (−1.8,-0.08); p=0.03]. No other significant correlations were found for overall or subcomponents of DGI scores. High rates of perceived food intolerances were observed in patients with an ileoanal pouch. However, only those with perceived dairy intolerances restricted their intake of lactose-containing dairy products. Additionally, patients with ileoanal pouch scored highly for overall diet quality but specific gaps in achieving better diet quality, particularly for diet variety were observed. These results provide some starting points for targeted dietary counselling to optimise nutritional health and potentially to improve pouch function these patients.
Ulcerative colitis (UC) is a chronic inflammatory disease involving the colon and rectum. One of the most modifiable environmental factors affecting UC severity is the patient’s dietary pattern. Although the role of dietary patterns on UC aetiology has been investigated previously, its relationship with disease severity has not yet been elucidated. This study examined the association between UC patients’ dietary patterns and disease severity. This cross-sectional study was conducted in 340 UC patients. Using an FFQ, food patterns were assessed. Twenty-five food categories were categorised based on the similarity of the nutrient composition of the food using the factor analysis method. A simple clinical colitis activity index was used to determine disease severity. Three dietary patterns were identified based on the factor analysis: healthy, unhealthy and Western dietary pattern. After adjusting for potential confounding factors, patients who were in the highest tertile of healthy dietary pattern compared with the lowest tertile were 92 % less likely to have severe UC (OR: 0·08; 95 % CI: 0·03, 0·22). Also, those in the highest tertile of the Western dietary pattern were 3·86 times more likely to have severe UC than those in the lowest tertile (OR: 3·86; 95 % CI: 1·86, 8·00). Even after controlling for confounding variables, unhealthy dietary pattern did not increase the risk of severe UC. Our data indicate the beneficial role of healthy dietary pattern in amelioration of disease severity in UC patients. To confirm this association, more studies are needed, especially prospective cohort studies.
Ulcerative Colitis (UC), a type of Inflammatory Bowel Disease (IBD), is a chronic, relapsing gastrointestinal condition with increasing global prevalence. The gut microbiome profile of people living with UC differs from healthy controls and this may play a role in the pathogenesis and clinical management of UC. Probiotics have been shown to induce remission in UC; however, their impact on the gut microbiome and inflammation is less clear. Anthocyanins, a flavonoid subclass, have shown anti-inflammatory and microbiota-modulating properties; however, this evidence is largely preclinical. To explore the combined effect and clinical significance of anthocyanins and a multi-strain probiotic, a 3-month randomised controlled trial will be conducted in 100 adults with UC. Participants will be randomly assigned to one of four groups: anthocyanins (blackcurrant powder) + placebo probiotic, probiotic + placebo fruit powder, anthocyanin + probiotic, or double placebo. The primary outcome is a clinically significant change in the health-related quality-of-life measured with the Inflammatory Bowel Disease Questionnaire-32. Secondary outcomes include shotgun metagenomic sequencing of the faecal microbiota, faecal calprotectin, symptom severity, and mood and cognitive tests. This research will identify the role of adjuvant anti-inflammatory dietary treatments in adults with UC and elucidate the relationship between the gut microbiome and inflammatory biomarkers in this disease, to help identify targeted individualised microbial therapies. ANZCTR registration ACTRN12623000630617.
Ulcerative colitis (UC) is an immune-mediated inflammation of the colonic mucosa. Gut microbiota dysbiosis may play a significant role in disease pathogenesis by causing shifts in metabolomic profiles within the gut. To identify differences and trends in the metabolomic profile of paediatric UC patients pre- and post-faecal microbiota transplants (FMT). Forty-six paediatric patients with mild-to-moderate UC and 30 healthy paediatric patients were enrolled in this study. Baseline stool samples were collected prior to FMT initiation and at months 1, 3, 6, and 12 post-FMT. Pediatric Ulcerative Colitis Activity Index (PUCAI) scores were calculated at baseline and months 1, 3, 6, and 12 after FMT. The average Bray–Curtis dissimilarities to healthy subjects decreased after FMT. In principal coordinate analysis plots, UC patients’ centroids drew nearer to healthy individuals. The variance explained by phenotype (Healthy versus UC) reduced and remained significant. From 1 to 3 months after FMT, PUCAI trends were statistically significant and decreasing. PUCAI scores remain flat starting 6 months after FMT. This study concludes that paediatric UC patients have a significantly different baseline metabolite profile than healthy controls. Although being time limited, FMT significantly altered these metabolite profiles and shifted them towards that of healthy controls.
In the UK, the incidence and prevalence of inflammatory bowel disease (IBD) is increasing in paediatric populations. Environmental factors including acute gastroenteritis episodes (AGE) may impact IBD development. Infant rotavirus vaccination has been shown to significantly reduce AGE. This study aims to explore the association between vaccination with live oral rotavirus vaccines and IBD development. A population-based cohort study was used, analysing primary care data from the Clinical Practice Research Datalink Aurum. Participants included children born in the UK from 2010 to 2015, followed from a minimum of 6 months old to a maximum of 7 years old. The primary outcome was IBD, and the primary exposure was rotavirus vaccination. Cox regression analysis with random intercepts for general practices was undertaken, with adjustment for potential confounding factors. In a cohort of 907,477 children, IBD was recorded for 96 participants with an incidence rate of 2.1 per 100,000 person-years at risk. The univariable analysis hazard ratio (HR) for rotavirus vaccination was 1.45 (95% confidence interval (CI) 0.93–2.28). Adjustment in the multivariable model attenuated the HR to 1.19 (95% CI 0.53–2.69). This study shows no statistically significant association between rotavirus vaccination and development of IBD. However, it provides further evidence for the safety of live rotavirus vaccination.
Computerized-adaptive testing (CAT) may increase reliability or reduce respondent burden for assessing patient-reported outcomes compared with static short forms (SFs). We compared CAT versus SF administration of the Patient-Reported Outcomes Measurement Information System® (PROMIS®) Pediatric measures in pediatric inflammatory bowel disease (IBD).
Methods:
Participants completed 4-item CAT, 5- or 6-item CAT, and 4-item SF versions of the PROMIS Pediatric measures. We compared average T-scores, intra-class correlations (ICCs), floor and ceiling effects, and standard error of measurement (SEM) across forms, along with mean effect sizes between active versus quiescent IBD disease activity groups.
Results:
Average PROMIS T-scores across forms were <3 points (minimally important difference) of each other. All forms correlated highly with each other (ICCs ≥0.90) and had similar ceiling effects, but the CAT-5/6 had lower floor effects. The CAT-5/6 had lower SEM than the CAT-4 and SF-4, and the CAT-4 had a lower SEM than the SF-4. Mean effect sizes were similar across forms when contrasting disease activity groups.
Conclusions:
The CAT and SF forms produced similar score results, but the CAT had better precision and lower floor effects. Researchers should consider PROMIS pediatric CAT if they anticipate that their sample will skew toward symptom extremes.
Time to evaluate diet quality and give dietary advice is limited in clinical inflammatory bowel disease (IBD) practice. The Eetscore is a web-based tool that assesses diet quality according to the Dutch dietary guidelines and provides personalised dietary advice. We aimed to assess diet quality of IBD patients using the Eetscore and to study changes in diet quality, health-related quality of life (HRQoL) and clinical disease activity over time. A prospective cohort study was performed in 195 adult IBD patients. Participants were invited to fill out questionnaires (Eetscore-FFQ, short Inflammatory Bowel Disease Questionnaire and Patient Harvey Bradshaw Index/Patient Simple Clinical Colitis Activity Index) at baseline and after 1 and 4 months. The Eetscore calculates diet quality based on sixteen food components (ten points per component, total score 0–160; the higher the better) and provides dietary advice per component based on the assessment. At baseline, mean diet quality was 98 (sd 19). Diet quality was positively associated with age, female sex and level of education. Component scores were highest for red meat, wholegrain products and sweetened beverages, and lowest for legumes, nuts and processed meat. Over time, diet quality increased to 107 (sd 21) at 4 months (P < 0·001). Each ten-point improvement in diet quality was associated with an increase in HRQoL (β = 0·4 (95 % CI (0·02, 0·7), P = 0·04). Clinical disease activity did not change. In conclusion, diet quality of IBD patients significantly improved following personalised dietary advice of the Eetscore. Improvement of diet quality was associated with a slight improvement in HRQoL. The Eetscore is a practical and useful tool to monitor and support a healthy diet in IBD patients.
The incidence rate of inflammatory bowel diseases is increasing in developed countries. As such there is an increasing demand for new therapies. The aim of this systematic review was to investigate whether there is evidence to support the use of helminth therapy for the management of Crohn's disease and ulcerative colitis. Four databases (PubMed, Embase, Medline and the Cochrane Central Register of Control Trials) were searched for primary evidence in the form of clinical studies. Nine studies were suitable for inclusion: five double-blind randomized control trials and four open-label studies. This review divided the results of the studies into two categories: (a) the efficacy of helminth therapy and (b) the safety of helminth therapy. Results regarding the efficacy were mixed and a conclusive answer could not be reached, as there was not enough evidence to rule out a placebo effect. More research is needed, particularly studies with control groups to address the possibility of a placebo effect. Despite this, all nine studies concluded helminth therapy was safe and tolerable, and therefore there is currently no evidence against further exploration of this treatment option.
The aetiology of inflammatory bowel disease (IBD) is multifactorial, with diet and gut microbiota playing an important role. Nonetheless, there are very few studies, particularly clinical research, which have explored the interaction between diet and gut microbiota. In the current review, we summarise the evidence from clinical trials exploring the interactions between the gut microbiota and diet in the management of IBD. Data from the effect of exclusive enteral nutrition (EEN) on the gut microbiota of children with active Crohn's disease (CD), receiving induction treatment, offer opportunities to understand the role of gut microbiota in underlying disease pathogenesis and develop novel dietary and pharmacological microbial therapeutics. In contrast, the evidence which links the effectiveness of food-based dietary therapies for IBD with mechanisms involving the gut microbiota is far less convincing. The microbial signals arising from these dietary therapies are inconsistent and vary compared to the effects of effective treatment with EEN in CD.
Inflammatory bowel disease (IBD) is a group of immune-mediated disorders characterised by a chronic, relapsing-remitting inflammation predominantly affecting the gastrointestinal tract. IBD is incurable, affecting people in their most productive years. IBD is historically seen as a disease of Westernised nations although in recent times other countries have seen an exponential rise in cases. Although the exact pathogenesis remains unclear, evidence suggests that microbiota changes play a critical role in IBD pathogenesis. Over the past two decades, IBD has become one of the most studied human conditions linked to the gut microbiota. However, deciphering the intricate link between the gut microbiota and therapeutic efficacy remains elusive. This review will summarise the current evidence relating to the gut microbiota and its involvement in IBD pathogenesis as well as the impact of IBD treatments including pharmaceutical-, nutraceutical- and microbial-focused regimens on the gut microbiota.
Extra virgin olive oil is often associated with anti-inflammatory and antioxidant properties. Its effects on inflammatory conditions such as ulcerative colitis (UC), however, have yet to be defined. As such, we aimed to conduct a systematic review and meta-analysis of studies investigating olive-based interventions in UC. A comprehensive database search for randomised controlled trials was performed between 9 July 2018 and 16 August 2018. Studies identified from search alerts were included up to 22 June 2020. Both individuals living with UC at any disease stage and murine models of UC were included in this review. No human trials meeting the eligibility criteria were identified, while nineteen animal studies comprised 849 murine models of UC were included in this review. Pooling of the data could not be performed due to heterogeneous outcomes; however, general trends favouring olive-based interventions were identified. Milder disease expression including weight maintenance, reduced rectal bleeding and well-formed stools favouring olive-based interventions was statistically significant in 16/19 studies, with moderate-to-large effect sizes (−0·66 (95 % CI −1·56, 0·24) to −12·70 (95 % CI −16·8, −8·7)). Olive-based interventions did not prevent the development of colitis-like pathologies in any study. In conclusion, effects of olive-based interventions on murine models of UC appear promising, with milder disease outcomes favouring the intervention in most trials and effect sizes suggesting potential clinical relevance. However, the lack of published randomised controlled human trials warrants further investigation to determine if these effects would translate to individuals living with UC.
Inflammatory bowel disease (IBD) [i.e., Crohn’s disease (CD) and ulcerative colitis (UC)] has been considered a relative contraindication for radiation therapy (RT) to the abdomen or pelvis, potentially preventing patients with a diagnosis of IBD from receiving definitive therapy for their malignancy.
Method:
Using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) conventions, a PubMed/MEDLINE literature search was conducted using the keywords RT, brachytherapy, inflammatory bowel disease, Crohn’s disease, ulcerative colitis and toxicity.
Results:
A total of 1,206 publications were screened with an addition of 8 studies identified through hand searching. Nineteen studies met the inclusion criteria for quantitative analysis. The total population across all studies was 497 patients, 50·5% having UC, 37% having CD and an additional 12·5% having unspecified IBD. Primary gastrointestinal malignancy (55%) followed by prostate cancer (40%) composed the bulk of the population. Acute and late grade 3 or greater gastrointestinal specific toxicity ranged from 0–23% to 0–13% respectively for those patients with IBD treated with RT to the abdomen or pelvis. In the literature reviewed, RT does not appear to increase fistula or stricture formation or IBD flares; however, one study did note RT to be a statistically significant risk factor for subsequent IBD flare on multivariate analysis.
Conclusions:
A review of reported acute and late toxicities suggests that patients with IBD should still be considered for definitive radiotherapy. Patient characteristics including IBD distribution relative to the irradiated field, inflammatory activity at the time of radiation, overall disease severity and disease phenotype in the case of CD (fistulising versus stricturing versus inflammatory only) should be considered on an individual basis when evaluating potential patients. When possible, advanced techniques with strict organ at risk dose constraints should be employed to limit toxicity in this patient population.
Inflammatory bowel disease (IBD) typically involves the large bowel, small bowel (ileum / jejunum), or both. Involvement of the upper GI tract is less common, although its frequency is uncertain because common causes of inflammation such as gastro-oesophageal reflux and Helicobacter pylori infection also require exclusion. In the setting of known IBD, upper GI inflammation generally favours Crohn’s disease over ulcerative colitis (UC), while granulomas strongly suggest involvement by IBD and indicate Crohn’s disease rather than UC. New upper GI inflammation may raise the possibility of IBD, while unexplained new upper GI granulomas require exclusion of Crohn’s disease. Unfortunately, few histological patterns apart from granulomas are specific or discriminant. Lymphocytic oesophagitis is a poorly defined entity associated with IBD and/or Crohn’s disease in some studies. Focally enhanced gastritis (FEG), though initially regarded as typical of Crohn’s disease, probably has limited value apart from perhaps predicting IBD in children. Rarely, UC patients develop a duodenitis resembling the colorectal changes histologically. UC may also be associated, infrequently, with characteristic patterns of gastritis. Compared with adults, children with IBD are more likely to have upper GI involvement, to develop GI granulomas, and to undergo investigation for upper GI disease. Overall, upper GI granulomas assist with the diagnosis and classification of IBD but few other upper GI features are discriminatory between IBD and other causes or between UC and Crohn’s disease.
Biopsy assessment of chronic idiopathic inflammatory bowel disease (IBD) is important for diagnosis, classification, determination of activity, documentation of anatomical extent and distribution, detection of complications, and diagnosis and grading of dysplasia. In addition, it may predict treatment response, clinical behaviour after therapy, and risk of future dysplasia. Microscopic features favouring IBD over non-IBD in biopsies include basal plasmacytosis and crypt architectural changes. Typically, ulcerative colitis (UC) extends from the rectum proximally and in a continuous fashion, while Crohn’s disease is discontinuous with intervening areas of sparing. Microscopic features that distinguish most reliably between Crohn’s disease and UC include granulomas (strongly favouring Crohn’s disease) and the distribution of architectural abnormalities/chronic inflammation between sites and within sites. However, discontinuity may also occur in UC. A caecal ‘patch’, i.e. a discontinuous area of caecal inflammation, is common in UC. Rectal sparing and other forms of discontinuity are more frequent in longstanding UC than new UC. The label IBD unclassified (IBDU) is available for difficult cases. In very early IBD (i.e., symptoms for <6 weeks), the architectural changes are often absent. IBD is common in patients with primary sclerosing cholangitis but may have unusual features. In summary, histological assessment in the light of the clinical and endoscopic findings plays an important role in optimising management of IBD.
There are significant differences between paediatric and adult gastrointestinal (GI) disease, and even the normal GI histology shows some variation.Excess eosinophils in the gut can be present in food allergies (frequent in children) but also in eosinophilic gastroenteritis. Inflammatory bowel disease (IBD) has some distinctive features when it presents in children. Genetic factors may play a greater role in pathogenesis, and the combination of clinical and histological criteria required for diagnosing Crohn’s Disease or ulcerative colitis (UC) is different. Atypical UC patterns are more common and clinical presentation of Crohn’s disease can also be different; the frequency of granulomas in Crohn’s disease is significantly higher in children. Inflammatory Bowel Disease Unclassified (IBDU) has its highest frequency in younger patients, possibly because of atypical characteristics of paediatric UC. Monogenic forms of IBD-like colitis typically develop during infancy or early childhood, an can have features of Crohn’s disease, UC or IBD unclassified. Histology is often indistinguishable from conventional IBD.Necrotising enterocolitis (NEC) primarily affects the small intestine of premature infants, with haemorrhagic necrosis of the bowel wall.Fibrosing colonopathy has been reported in children exposed to high doses of pancreatic enzymes and is characterised by bowel wall thickening, submucosal fibrosis and chronic mucosal inflammation.
The development of the ileal pouch anal anastomosis (IPAA) has led to significant improvements in the quality of life for patients after proctocolectomy. The complex anatomy of the pouch requires a systematic examination of the different IPAA components at pouchoscopy and sampling of different histological zones, i.e. pre-pouch, pouch, rectal cuff, and anal mucosa. The main roles of the pathologist are to corroborate a clinical diagnosis of pouchitis, to identify secondary causes of inflammation when present, to be aware of the differential diagnosis, and to exclude histologically identifiable complications such as CMV infection, dysplasia and malignancy. Assessment can be difficult for several reasons, e.g. the anatomical location of a biopsy is not always obvious, adaptive changes may occur that lead to alterations in mucosal morphology, and Crohn’s-like changes may occur as a consequence of pouchitis and may cause diagnostic confusion.
The aim of the present paper is to review the effects of non-digestible oligosaccharides (NDO) on immunity, focusing on their microbiota-independent mechanisms of action, as well as to explore their potential beneficial role in inflammatory bowel diseases (IBD). IBD are chronic, inflammatory conditions of the gastrointestinal tract. Individuals with IBD have an aberrant immune response to commensal microbiota, resulting in extensive mucosal inflammation and increased intestinal permeability. NDO are prebiotic fibres well known for their role in supporting intestinal health through modulation of the gut microbiota. NDO reach the colon intact and are fermented by commensal bacteria, resulting in the production of SCFA with immunomodulatory properties. In disease states characterised by increased gut permeability, prebiotics may also bypass the gut barrier and directly interact with intestinal and systemic immune cells, as demonstrated in patients with IBD and in infants with an immature gut. In vitro models show that fructooligosaccharides, inulin and galactooligosaccharides exert microbiota-independent effects on immunity by binding to toll-like receptors on monocytes, macrophages and intestinal epithelial cells and by modulating cytokine production and immune cell maturation. Moreover, animal models and human supplementation studies demonstrate that some prebiotics, including inulin and lactulose, might reduce intestinal inflammation and IBD symptoms. Although there are convincing preliminary data to support NDO as immunomodulators in the management of IBD, their mechanisms of action are still unclear and larger standardised studies need to be performed using a wider range of prebiotics.
Gluten is only partially digested by intestinal enzymes and can generate peptides that can alter intestinal permeability, facilitating bacterial translocation, thus affecting the immune system. Few studies addressed the role of diet with gluten in the development of colitis. Therefore, we investigate the effects of wheat gluten-containing diet on the evolution of sodium dextran sulphate (DSS)-induced colitis. Mice were fed a standard diet without (colitis group) or with 4·5 % wheat gluten (colitis + gluten) for 15 d and received DSS solution (1·5 %, w/v) instead of water during the last 7 d. Compared with the colitis group, colitis + gluten mice presented a worse clinical score, a larger extension of colonic injury area, and increased mucosal inflammation. Both intestinal permeability and bacterial translocation were increased, propitiating bacteria migration for peripheral organs. The mechanism by which diet with gluten exacerbates colitis appears to be related to changes in protein production and organisation in adhesion junctions and desmosomes. The protein α-E-catenin was especially reduced in mice fed gluten, which compromised the localisation of E-cadherin and β-catenin proteins, weakening the structure of desmosomes. The epithelial damage caused by gluten included shortening of microvilli, a high number of digestive vacuoles, and changes in the endosome/lysosome system. In conclusion, our results show that wheat gluten-containing diet exacerbates the mucosal damage caused by colitis, reducing intestinal barrier function and increasing bacterial translocation. These effects are related to the induction of weakness and disorganisation of adhesion junctions and desmosomes as well as shortening of microvilli and modification of the endocytic vesicle route.
Despite the fact that inflammatory bowel disease (IBD) has still no recognised therapy, treatments which have proven at least mildly successful in improving IBD symptoms include anti-inflammatory drugs and monoclonal antibodies targeting pro-inflammatory cytokines. Resveratrol, a natural (poly)phenol found in grapes, red wine, grape juice and several species of berries, has been shown to prevent and ameliorate intestinal inflammation. Here, we discuss the role of resveratrol in the improvement of inflammatory disorders involving the intestinal mucosa. The present review covers three specific aspects of resveratrol in the framework of inflammation: (i) its content in food; (ii) its intestinal absorption and metabolism; and (iii) its anti-inflammatory effects in the intestinal mucosa in vitro and in the very few in vivo studies present to date. Actually, if several studies have shown that resveratrol may down-regulate mediators of intestinal immunity in rodent models, only two groups have performed intervention studies in human subjects using resveratrol as an agent to improve IBD conditions. The effects of resveratrol should be further investigated by conducting well-designed clinical trials, also taking into account different formulations for the delivery of the bioactive compound.