Evidence-Based and Emerging Diet Recommendations for Small Bowel Disorders.

Diet plays a key role in the manifestation and severity of gastrointestinal symptoms, with increasing research interest on the role of diet in small bowel disorders. There are predominantly 3 small bowel conditions that have potential dietary interventions. Self-reported nonceliac gluten/wheat sensitivity is prevalent. Although gluten is believed to be a potential trigger for symptoms, other components of wheat may also be triggers, including fructans, alpha-amylase trypsin inhibitors, and wheat germ agglutinins. The diagnosis can be challenging, given the lack of validated biomarkers. A gluten-free diet that excludes the abovementioned triggers is the cornerstone of treatment; however, unlike celiac disease, there is uncertainty about the level of adherence or whether the gluten-free diet is a lifelong intervention. Several primary gastrointestinal disorders are associated with an increase in inflammatory cells including eosinophils. Diet seems to be an important driver of disease pathogenesis in eosinophilic gastroenteritis, with elimination and elemental diets showing promise in management, with further robust trials required. Small intestinal bacterial overgrowth is an example of microbial dysbiosis, with renewed interest in diet being postulated to cause an adaptive change of the microbes colonizing the small intestine. However, the diagnosis of small intestinal bacterial overgrowth is limited by a lack of sensitive and specific tests, with significant knowledge gaps in relation to therapeutic measures to manage and cure small intestinal bacterial overgrowth. Currently, antimicrobials are the established management option. There have been significant clinical advances in dietary interventions related to the small bowel, but this area is currently a novel and advancing field for both patients and clinicians.

Type 2 and type 17 effector cells are increased in the duodenal mucosa but not peripheral blood of patients with functional dyspepsia.

Background: Functional dyspepsia is characterised by chronic symptoms of post-prandial distress or epigastric pain not associated with defined structural pathology. Increased peripheral gut-homing T cells have been previously identified in patients. To date, it is unknown if these T cells were antigen-experienced, or if a specific phenotype was associated with FD. Objective: This study aimed to characterise T cell populations in the blood and duodenal mucosa of FD patients that may be implicated in disease pathophysiology. Methods: We identified duodenal T cell populations from 23 controls and 49 Rome III FD patients by flow cytometry using a surface marker antibody panel. We also analysed T cell populations in peripheral blood from 37 controls and 61 patients. Where available, we examined the number of duodenal eosinophils in patients and controls. Results: There was a shift in the duodenal T helper cell balance in FD patients compared to controls. For example, patients had increased duodenal mucosal Th2 populations in the effector (13.03 ± 16.11, 19.84 ± 15.51, p=0.038), central memory (23.75 ± 18.97, 37.52 ± 17.51, p=0.007) and effector memory (9.80±10.50 vs 20.53±14.15, p=0.001) populations. Th17 populations were also increased in the effector (31.74±24.73 vs 45.57±23.75, p=0.03) and effector memory (11.95±8.42 vs 18.44±15.63, p=0.027) subsets. Peripheral T cell populations were unchanged between FD and control. Conclusion: Our findings identify an association between lymphocyte populations and FD, specifically a Th2 and Th17 signature in the duodenal mucosa. The presence of effector and memory cells suggest that the microinflammation in FD is antigen driven.

Wheat Sensitivity and Functional Dyspepsia: A Pilot, Double-Blind, Randomized, Placebo-Controlled Dietary Crossover Trial with Novel Challenge Protocol.

Introduction: Functional dyspepsia (FD), characterised by symptoms of epigastric pain or early satiety and post prandial distress, has been associated with duodenal eosinophilia, raising the possibility that it is driven by an environmental allergen. Non-coeliac gluten or wheat sensitivity (NCG/WS) has also been associated with both dyspeptic symptoms and duodenal eosinophilia, suggesting an overlap between these two conditions. The aim of this study was to evaluate the role of wheat (specifically gluten and fructans) in symptom reduction in participants with FD in a pilot randomized double-blind, placebo controlled, dietary crossover trial. Methods: Patients with Rome III criteria FD were recruited from a single tertiary centre in Newcastle, Australia. All were individually counselled on a diet low in both gluten and fermentable oligo-, di-, mono-saccharides, and polyols (FODMAPs) by a clinical dietitian, which was followed for four weeks (elimination diet phase). Those who had a >30% response to the run-in diet, as measured by the Nepean Dyspepsia Index, were then re-challenged with 'muesli' bars containing either gluten, fructan, or placebo in randomised order. Those with symptoms which significantly reduced during the elimination diet, but reliably reappeared (a mean change in overall dyspeptic symptoms of >30%) with gluten or fructan re-challenge were deemed to have wheat induced FD. Results: Eleven participants were enrolled in the study (75% female, mean age 43 years). Of the initial cohort, nine participants completed the elimination diet phase of whom four qualified for the rechallenge phase. The gluten-free, low FODMAP diet led to an overall (albeit non-significant) improvement in symptoms of functional dyspepsia in the diet elimination phase (mean NDI symptom score 71.2 vs. 47.1, p = 0.087). A specific food trigger could not be reliably demonstrated. Conclusions: Although a gluten-free, low-FODMAP diet led to a modest overall reduction in symptoms in this cohort of FD patients, a specific trigger could not be identified. The modified Salerno criteria for NCG/WS identification trialled in this dietary rechallenge protocol was fit-for-purpose. However, larger trials are required to determine whether particular components of wheat induce symptoms in functional dyspepsia.

Duodenal eosinophils as predictors of symptoms in coeliac disease: a comparison of coeliac disease and non-coeliac dyspeptic patients with controls.

Introduction: Duodenal eosinophilia is a key feature of functional dyspepsia, particularly in those with early satiety. Duodenal eosinophilia is also recognised in coeliac disease, although its relevance to symptoms is not understood. We aimed to determine if duodenal eosinophilia is present in patients with coeliac disease presenting with dyspepsia, and whether other histological characteristics were associated with clinical features on presentation.Methods: The coeliac study population comprised 61 patients with a new presentation of coeliac disease to a single centre from 2003 to 2013. A standard symptom assessment was documented for all patients. The control population (55 adults) presenting for endoscopy without coeliac disease was drawn from the same centre with similar demographics for age and gender. Duodenal biopsies from both groups were assessed for eosinophil counts and histological features.Results: Dyspepsia was present in 18.0% of coeliac patients and early satiety in 24.6%. The eosinophil counts were significantly higher in the stomach (12.1/mm2 vs. 4.0/mm2, p < .001) and duodenum (60.4/mm2 vs. 18.0/mm2, p < .001) of coeliac patients compared with controls. There was no significant difference in the mean duodenal eosinophil count in coeliac disease with and without early satiety (55.4/mm2 vs. 66.9/mm2, p = .51). Duodenal eosinophilia was not associated with the severity of coeliac enteropathy. The degree of villous atrophy was associated with iron deficiency at presentation (p = .01), but not symptoms.Conclusions: Although duodenal eosinophil counts are higher in coeliac disease than controls, we were not able to demonstrate an association with presenting symptoms or markers of disease severity.

Tangible pathologies in functional dyspepsia.

Functional dyspepsia (FD) is a common, costly and complex disease, currently defined by symptoms, directed by the Rome consensus on functional bowel disorders, which has evolved over the past two decades. Symptoms include abdominal pain, are often meal related and there are two major subtypes, postprandial distress syndrome and epigastric pain syndrome, not attributed to pathology. Increasingly it is recognised that tangible pathologies occur in FD, for example Helicobacter pylori and other pathophysiological changes, most notably duodenal pathology, namely duodenal eosinophilia, permeability alterations, structural neuronal changes and microbial duodenal dysbiosis. This has led to the idea that FD is a true disease entity and triggers of this condition based on epidemiology studies point towards allergy, immune disorders and infection. Anxiety and depression may precede or follow FD, (brain-gut/gut-brain disorders). Currently most therapies for FD are inadequate but underlying pathology may lead to targeted treatment success as an attainable goal.

Oesophageal food bolus obstruction and eosinophilic oesophagitis.

Eosinophilic oesophagitis (EoE) is now a well-recognised cause of dysphagia and food bolus obstruction (FBO). The diagnosis requires histologic confirmation, and the yield is greatest when at least 4 to 6 oesophageal biopsies are taken from different sites. Previous case reports of FBO have demonstrated a low biopsy rate, and as such cases of EoE may have been missed. In this review, the medical records of 123 patients aged 18 years or older, who had presented with FBO over a 2 year period, were reviewed. EoE was the most common diagnosis, and was found in 81.3% of patients with FBO aged 40 years or less. 45.5% of patients with FBO were biopsied, and of those, 33.9% were confirmed to have had at least 4 biopsies. EoE is a common cause of FBO and requires appropriate oesophageal sampling to confirm the diagnosis. Cases of EoE may otherwise be missed.

Eosinophilic colitis and colonic eosinophilia.

PURPOSE OF REVIEW: Eosinophilic colitis is a rare condition, with a prevalence rate in the USA of 2-3/100 000 persons (0.003%), but diagnosed in 0.1% of biopsies in those colonoscoped for diarrhoea. Secondary colonic eosinophilia is more common and associated with systemic, colonic and infectious diseases. In this review, the latest advances in diagnosis, treatment and prognosis are summarized and discussed. RECENT FINDINGS: What constitutes a 'normal' count of eosinophils is poorly documented but there are recent studies that establish normal colonic eosinophil ranges as well as distinguishing histological and clinical findings in primary eosinophilic colitis and secondary colonic eosinophilia in children and adults. Primary eosinophilic colitis is rare, relatively straightforward to diagnose, but may be difficult to treat. Colonic eosinophilia may be overt in parasite infection and connective tissue disease. More subtle, secondary colonic eosinophilia is a useful biomarker for gastrointestinal diseases, such as inflammatory bowel disease, colonic spirochaetosis and collagenous colitis, but the eosinophilia may more often be overlooked. A limited number of drugs are also known to cause left sided colonic eosinophilia such as clopidogrel, ibuprofen and oestroprogestinic agents. SUMMARY: Advances in our understanding of primary eosinophilic colitis and secondary colonic eosinophilia is progressing and if present, colonic eosinophilia should point the clinician and pathologist to a list of differential diagnoses worth considering to direct optimal management.

A Serological Diagnosis of Coeliac Disease Is Associated with Osteoporosis in Older Australian Adults.

Previously thought to be mainly a disorder of childhood and early adult life, coeliac disease (CeD) is increasingly diagnosed in older adults. This may be important given the association between CeD and osteoporosis. The primary aim of this study was to determine the seroprevalence of undiagnosed CeD (‘at-risk serology’) in an older Australian community and relate this to a diagnosis of osteoporosis and fractures during a follow-up period of 12 years. We included participants from the Hunter Community Study (2004⁻2007) aged 55⁻85, who had anti-tissue transglutaminase (tTG) titres, human leukocyte antigen (HLA) genotypes, and bone mineral density measurements at baseline. Follow-up data included subsequent diagnosis of CeD and fractures using hospital information. ‘At-risk’ serology was defined as both tTG and HLA positivity. Complete results were obtained from 2122 patients. The prevalence of ‘at-risk’ serology was 5%. At baseline, 3.4% fulfilled criteria for a diagnosis of osteoporosis. During a mean of 9.7 years of follow-up, 7.4% of the cohort suffered at least one fracture and 0.7% were subsequently diagnosed with CeD. At-risk serology was significantly associated with osteoporosis in a multivariate model (odds ratio 2.83, 95% confidence interval 1.29⁻6.22); there was insufficient power to look at the outcome of fractures. The results of this study demonstrate that at-risk CeD serology was significantly associated with concurrent osteoporosis but not future fractures. Most individuals with a serological diagnosis of CeD were not diagnosed with CeD during the follow-up period according to medical records. Coeliac disease likely remains under-diagnosed.

Wheat Intolerance and Chronic Gastrointestinal Symptoms in an Australian Population-based Study: Association Between Wheat Sensitivity, Celiac Disease and Functional Gastrointestinal Disorders.

OBJECTIVES: Wheat avoidance in the absence of celiac disease (CD) is common but occurrence of concurrent functional gastrointestinal disorders (FGIDs) in this group is uncertain. The aims of this study were to determine the prevalence of self-reported wheat or gluten sensitivity and doctor diagnosed CD in an Australian population, define the associated gastrointestinal (GI) symptoms and FGIDs, and determine the relationship between self-reported wheat sensitivity, demographic and medical factors. METHODS: A total of 3542 people randomly selected from the Australian population returned a mail survey which contained questions on wheat avoidance, GI symptoms, demographic, medical, and lifestyle factors. We defined self-reported wheat sensitivity as people who reported gastrointestinal symptoms on ingestion of wheat based foods, but did not suffer from celiac disease, inflammatory bowel disease or colorectal cancer. Functional dyspepsia (FD) and irritable bowel syndrome (IBS) were diagnosed by Rome III criteria. CD status was self-reported. RESULTS: The prevalence of self-reported wheat sensitivity in this cohort was 14.9% (95% CI 13.7-16.2). The prevalence of CD was 1.2% (95%CI 0.8-1.6). Doctor diagnosed CD was significantly associated with a diagnosis of FD (OR 3.35, 95%CI 1.72-6.52) and IBS (OR 2.28, 95%CI 1.08-4.81). Those with self-reported wheat sensitivity were more likely to report multiple abdominal symptoms (of the 18 assessed) than those without (3.9 symptoms with self-reported wheat sensitivity vs. 1.6 without, p = 0.0001). In a multivariate analysis, self-reported wheat sensitivity was independently associated with IBS (OR 3.55, 95%CI 2.71-4.65) and FD (1.48, 95%CI 1.13-1.94). CONCLUSIONS: Self-reported wheat sensitivity is common, with a prevalence of 14.9% in this cohort. There is a strong association between both celiac disease and self-reported wheat sensitivity, and chronic gastrointestinal symptoms, as well as a diagnosis of FD and IBS.

Effect of the gluten-free diet on cardiovascular risk factors in patients with coeliac disease: A systematic review.

BACKGROUND AND AIMS: A gluten-free diet (GFD), the mainstay of treatment for celiac disease, is being increasingly adopted by people without this condition. The long-term health effects of this diet, apart from its beneficial effect on enteropathy in celiac disease, are unclear. Concerns exist that the GFD may result in micronutrient deficiencies, increased exposure to toxins such as arsenic, and an increased cardiovascular risk. This systematic review addresses the effect of the GFD on several modifiable cardiovascular risk factors. METHODS: A systematic search of the literature addressing the GFD and blood pressure, glycaemia, body mass index, waist circumference, and serum lipids in patients before and after adoption of a GFD was conducted using the MEDLINE, EMBASE, PSYCInfo, and the Cochrane Central Register of Controlled Trials (CENTRAL) databases. Two authors performed abstract and full text screening, and quality assessment. RESULTS: A total of 5372 articles were identified, from which 27 were included. Lack of control groups in all but one study prevented meta-analysis of results. Overall study quality was low and restricted to patients with celiac disease. Consistent findings across studies included an increase in total cholesterol, high density lipoprotein, fasting glycaemia, and body mass index (while remaining within the healthy weight range). Significant changes in low density lipoprotein, triglycerides, and blood pressure were not consistently reported. CONCLUSIONS: A GFD alters certain cardiovascular risk factors in patients with celiac disease, but the overall effect on cardiovascular risk is unclear. Further studies are warranted.

Perineal tap water burns in the elderly: at what cost?

BACKGROUND: Burn injuries are expensive to treat. Burn injuries have been found to be difficult to treat in elderly patients than their younger counterparts. This is likely to result in higher financial burden on the healthcare system; however, no population-specific study has been conducted to ascertain the inpatient treatment costs of elderly patients with hot tap water burns. METHODS: Six elderly patients (75-92 years) were admitted for tap water burns at Concord Hospital during 2010. All costs incurred during their hospitalization were followed prospectively, and were apportioned into 'direct' and 'indirect' costs. Direct costs encompassed directly measurable costs, such as consumables used on the ward or in theatres, and indirect costs included hospital overheads, such as bed and theatre costs. RESULTS: Three males and three females admitted with burns to the buttocks, legs or feet. Total burn surface area (TBSA) ranged from 9-21% (mean 12.8%). Length of stay ranged from 26-98 days (mean 46 days). One patient died, and four required surgical management or grafting. Total inpatient costs ranged from $69 782.33 to $254 652.70 per patient (mean $122 800.20, standard deviation $67 484.46). TBSA was directly correlated with length of stay (P < 0.01) and total cost (P < 0.01). CONCLUSION: Hot water burns among the elderly are associated with high treatment costs, which are proportional to the size of the burn. The cost of treating this cohort is higher than previously reported in a general Australian burn cohort.