Optimal Design of Clinical Trials of Dietary Interventions in Disorders of Gut-Brain Interaction.

There is accumulating evidence for the fundamental role of diet in the integrated care of disorders of gut-brain interaction. Food is a complex mixture of components with individual, synergistic, and antagonistic effects, compared with the relative purity of a pharmaceutical. Food is also an inherent part of individuals' daily lives, and food choice is strongly tied to food preferences, personal beliefs, cultural and religious practices, and economic status, which can influence its ability to function as a therapeutic intervention. Hence, randomized controlled trials of dietary interventions carry unique methodological complexities that are not applicable to pharmaceutical trials that if disregarded can pose significant risk to trial quality. The challenges of designing and delivering the dietary intervention depend on the type of intervention (i.e., nutrient vs food supplementation or whole-diet intervention). Furthermore, there are multiple modes of delivery of dietary interventions, each with their own advantages (e.g., the high precision of feeding trials and the strong clinical applicability of dietary counseling trials). Randomized placebo-controlled trials of dietary interventions are possible with sufficient attention to their design and methodological nuances. Collaboration with experts in nutrition and dietetics is essential for the planning phase; however, even with expert input, not all challenges can be overcome. Researchers undertaking future dietary trials must be transparent in reporting these challenges and approaches for overcoming them. This review aims to provide guiding principles and recommendations for addressing these challenges to facilitate the conduct and reporting of high-quality trials that inform and improve clinical practice.

Therapeutic Potential of the 4 Strategies to SUlfide-REduction (4-SURE) Diet in Adults with Mild to Moderately Active Ulcerative Colitis: An Open-Label Feasibility Study.

BACKGROUND: Diet therapy may bridge the therapeutic gap in ulcerative colitis (UC). OBJECTIVES: The novel 4-SURE diet (4-strategies-to-SUlfide-REduction), designed to modulate colonic fermentation and influence production of excess hydrogen sulfide, was examined in a feasibility study for tolerability, clinical efficacy, and effects on microbial endpoints. METHODS: Adults aged ≥18 y old with mild to moderately active UC were advised to increase intake of fermentable fibers, restrict total and sulfur-containing proteins, and avoid specific food additives for 8 wk. The primary outcome was tolerability of diet [100-mm visual analogue scale (VAS) with 100-mm being intolerable]. Secondary exploratory outcomes were self-reported adherence (always adherent ≥76-100%), clinical and endoscopic response (reduction in partial Mayo ≥2 and Mayo endoscopic subscore ≥1), modulation of fecal characteristics including markers of protein and carbohydrate fermentation, and food-related quality of life (IBD-FRQoL-29). Primary analysis was by intention to treat, performed using paired t and Wilcoxon signed-rank statistical tests. RESULTS: Twenty-eight adults with UC [mean (range) age: 42 (22-72) y, 15 females, 3 proctitis, 14 left-sided, and 11 extensive] were studied. Prescribed dietary targets were achieved overall. The diet was well tolerated (VAS: 19 mm; 95% CI: 7, 31 mm) with 95% frequently or always adherent. Clinical response occurred in 13 of 28 (46%) and endoscopic improvement in 10 of 28 participants (36%). Two participants (7%) worsened. Fecal excretion of SCFAs increased by 69% (P < 0.0001), whereas the proportion of branched-chain fatty acids to SCFAs was suppressed by 27% (-1.34%; 95% CI: -2.28%, -0.40%; P = 0.007). The FRQoL improved by 10 points (95% CI: 4, 16; P < 0.001). CONCLUSIONS: The 4-SURE dietary strategy is considered tolerable and an acceptable diet by adults with mild to moderately active UC. The dietary teachings achieved the prescribed dietary and fecal targets. Given signals of therapeutic efficacy, further evaluation of this diet is warranted in a placebo-controlled trial. This trial was registered at https://www.anzctr.org.au (Australian New Zealand Clinical Trials Registry) as ACTRN12619000063112.

Dietary Guidance From the International Organization for the Study of Inflammatory Bowel Diseases.

Recent evidence points to a plausible role of diet and the microbiome in the pathogenesis of both Crohn's disease (CD) and Ulcerative Colitis (UC). Dietary therapies based on exclusion of table foods and replacement with nutritional formulas and/or a combination of nutritional formulas and specific table foods may induce remission in CD. In UC, specific dietary components have also been associated with flare of disease. While evidence of varying quality has identified potential harmful or beneficial dietary components, physicians and patients at the present time do not have guidance as to which foods are safe, may be protective or deleterious for these diseases. The current document has been compiled by the nutrition cluster of the International Organization for the Study of Inflammatory Bowel Diseases (IOIBD) based on the best current evidence to provide expert opinion regarding specific dietary components, food groups and food additives that may be prudent to increase or decrease in the diet of patients with inflammatory bowel diseases to control and prevent relapse of inflammatory bowel diseases.

Food Therapy in Sinosphere Asia.

Traditional Chinese Food Therapy has long been an integral part of dietary practices in Sinosphere Asia. This therapy is defined by the classification of foods into cooling (Yin) and heaty (Yang) and the manipulation of dietary intake of these foods as a therapeutic strategy for chronic diseases. Both functional dyspepsia (FD) and irritable bowel syndrome (IBS) are chronic, functional gut disorders widely prevalent in Sinosphere Asia. Diet is increasingly recognized as a symptom trigger in FD and IBS, and the evidence suggesting the utility of diet therapies as front-line management is growing, particularly in the West. Specifically, a diet low in Fermentable, Oligosaccharides, Disaccharides, Monosaccharides, and Polyols is an efficacious therapy for patients with IBS. In contrast, a proportion of patients with IBS in Sinosphere Asia utilize Chinese Food Therapy for symptom management. Chinese Food Therapy provides an attractive target for integration with evidence-based Western dietary therapies as a management strategy in FD and IBS. However, significant gaps in research exist with the utility of Chinese Food Therapy that first need to be addressed. This includes a lack of standardization for heaty and cooling classification, limited mechanistic rationale or clinical studies supporting its efficacy in FD and IBS, and the lack of an ideal practitioner for implementation of Chinese Food Therapy. Hence, the review provides a summary of the role of diet and nutrition in Sinosphere Asia with an emphasis on FD and IBS, and an examination of how modern dietary practices may be able to be integrated into practices in this region.

Breath Hydrogen Testing in East and Southeast Asia.

Breath hydrogen tests are popular, noninvasive tests for the assessment of carbohydrate fermentation in patients with irritable bowel syndrome (IBS) and functional dyspepsia (FD). There is limited information regarding the utility of breath hydrogen and methane tests in IBS and FD patients in East and Southeast Asia. This review aims to summarize current literature about common indications of breath testing in this region, the genesis of functional gastrointestinal symptoms by provocative breath testing and provide suggestions for correct use. The most common testing indication is the assessment of lactose intolerance, followed by small intestinal bacterial overgrowth (SIBO) and differentiation of intestinal gas profiles in research setting. Studies in this region not only documented a high prevalence of lactose malabsorption but a population, both healthy and IBS, that is highly symptomatic to typical lactose intakes. Breath hydrogen assessment of other fermentable carbohydrates (FODMAPs) are fairly uncommon, whereas methane breath testing is almost nonexistent. Cumulative hydrogen production following lactulose was also not excessive in IBS patients compared with controls. The evidence however, for the detection of SIBO suggests limited reliability in the use of lactulose or glucose breath testing alone and inconclusive data on its correlation with symptoms. Conversely, little has been carried out in FD. In conclusion, breath testing should be limited in the predicting patients with SIBO for directing clinical management but can be considered in the objective assessment of lactose malabsorption within a low FODMAP diet. Recommendations to improve the interpretation of breath testing in research were also provided.

Dietary Interventions in Liver Cirrhosis.

Liver cirrhosis is associated with significant nutritional risks that often result in serious hepatic complications and poor survival rates. Diet is an important but underutilized aspect in the treatment modality of cirrhosis. Therefore, the aims of this review are to ascertain nutritional risks associated with its pathophysiology and to summarize existing evidence that support dietary recommendations for managing this patient population. Alterations in substrate utilization for energy production is a main feature of liver cirrhosis, resulting in increased catabolism of protein stores and a predisposition toward protein-energy malnutrition, even in the early stages of the disease. The body of evidence suggests that a high energy and protein (>1.2 g/kg body weight/d) diet consumed frequently and late in the evening is effective in improving nutritional status of these patients and has been associated with improved hospitalization and mortality rates. The use of branched-chain amino acid supplementation shows promise in reducing cirrhosis-related complications but are currently limited by adverse gastrointestinal symptoms and poor palatability. Furthermore exploration of dietary manipulation of branched-chain amino acid warrants further examination. Evidence is also accumulating that protein intake should not be restricted in patients with hepatic encephalopathy with earlier studies of protein restriction neglecting to account for the relative increase in fermentable fiber which would reduce the absorption of ammonia into the portal system in a way similar to supplementation with lactulose. Finally, a major finding of this review is the need to improve the quality and quantity of dietary intervention studies for patients with liver cirrhosis, particularly with the use of partial or whole dietary sources. In conclusion, dietary management of cirrhosis is not a one-size fits all approach but should be implemented earlier on in the treatment algorithm to improve the clinical prognosis of cirrhosis.

Dietary management of adults with IBD - the emerging role of dietary therapy.

Historically, dietitians played a minor part in the management of inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis. Patients were commonly referred for consequences of uncontrolled disease, such as malnutrition and bowel obstruction risk. Today, dietitians are fundamental members of the multidisciplinary IBD team, from educating on the role of diet at diagnosis and throughout the lifespan of a patient with IBD to guiding primary induction therapy. This aspect is reflected in published guidelines for IBD management, which previously placed diet as only a minor factor, but now have diet-specific publications. This Review describes a four-step approach in a dietitian's assessment and management of diet in patients with IBD: (1) identifying and correcting nutritional gaps and dietary imbalances; (2) considering diet to treat active disease with the use of exclusive enteral nutrition (EEN) or emerging diets that could replace EEN; (3) using therapeutic diets to control existing complications of IBD, such as reduced fibre to prevent bowel obstruction in stricturing disease or a fermentable oligosaccharides, disaccharides, monosaccharides and polyols diet to manage co-existing functional gut symptoms; and (4) considering the role of diet in preventing IBD development in high-risk populations.