Food-Based Interventions as Therapy for Inflammatory Bowel Disease: Important Steps in Diet Trial Design and Reporting of Outcomes.

Diet therapy for inflammatory bowel disease (IBD) is an international research priority but guidance for IBD-specific diet trial design is lacking. This review critically evaluates key elements of prospective IBD food-based intervention trials and identifies gaps. Electronic databases were searched for interventional IBD diet studies. Prospective primary studies/trials were included if used food-based dietary strategies. Forty studies/trials evaluating 29 food-based strategies as therapy for IBD were identified. Considerable heterogeneity in diets, trial design, and methodology exists. Thirty-one trials (78%) intended the diet to modulate inflammation but 14/31 (46%) did not have a primary endpoint measuring an objective change in inflammatory activity and 20/31 (65%) controlled for medication stability prior to application of diet at baseline. Higher-quality IBD diet trials used symptom-based assessment tools coupled with an objective evaluation of inflammatory activity. Dietary advice trials are the most common. One-third of trials developed and administered diet education without a dietitian. Evaluation and reporting on adherence to diet therapy occurred in <60% of trials. Failure to include or report on key elements of trial design reduced the interpretability and validity of the results. This is a considerable limitation to advancing scientific knowledge in this area. Diet therapy trials should adhere to similar rigorous quality standards used to develop other IBD therapies. Therefore, a set of practical recommendations was generated to provide the authors' perspective to help inform the future design of high-quality IBD diet trials.

High-quality inflammatory bowel disease (IBD) diet trials are lacking and existing trials are fraught with methodological flaws. This review is intended to assist clinician-researchers in the design and conduct of future food-based intervention trials to raise the quality of IBD diet research.

Revolution in diet therapy for inflammatory bowel disease.

Until recently, diet as a therapeutic tool to treat inflammatory bowel disease (IBD) has not been proven effective. Nearly a century in the making we are in the grips of a revolution in diet therapies for IBD, driven by emerging data revealing diet as a key environmental factor associated with IBD susceptibility, and observational studies suggesting that dietary intake may play a role in the disease course of established IBD. This review summarizes the current evidence for diets trialed as induction and maintenance therapy for IBD. For Crohn's disease, exclusive enteral nutrition and the Crohn's disease exclusion diet with partial enteral nutrition are supported by emerging high-quality evidence as induction therapy, but are short-term approaches that are not feasible for prolonged use. Data on diet as maintenance therapy for Crohn's disease are conflicting, with some studies supporting fortification, and others suppression, of certain food components. For ulcerative colitis, data are not as robust for diet as induction and maintenance therapy; however, consistent themes are emerging, suggesting benefits for diets that are plant-based, high in fiber and low in animal protein. Further studies for both Crohn's disease and ulcerative colitis are eagerly awaited, which will allow specific recommendations to be made. Until this time, recommendations default to population based healthy eating guidelines.

Composite Assessment Using Intestinal Ultrasound and Calprotectin Is Accurate in Predicting Histological Activity in Ulcerative Colitis: A Cohort Study.

BACKGROUND: Beyond endoscopic remission, histological remission in ulcerative colitis (UC) is predictive of clinical outcomes. Intestinal ultrasound (IUS) may offer a noninvasive surrogate marker for histological activity; however, there are limited data correlating validated ultrasound and histological indices. AIM: Our aim was to determine the correlation of IUS activity in UC with a validated histological activity index. METHODS: Twenty-nine prospective, paired, same-day IUS/endoscopy/histology/fecal calprotectin (FC) cases were included. Intestinal ultrasound activity was determined using the Milan Ultrasound Criteria, histological activity using the Nancy Histological Index, endoscopic activity using Mayo endoscopic subscore and Ulcerative Colitis Endoscopic Index of Severity, and clinical activity using the Simple Clinical Colitis Activity Score. RESULTS: Histological activity demonstrated a significant linear association with overall IUS activity (coefficient 0.14; 95% CI, 0.03-0.25; P = .011). Intestinal ultrasound activity was also significantly associated with endoscopic activity (0.32; 95% CI, 0.14-0.49; P < 0.001), total Mayo score (0.31; 95% CI, 0.02-0.60; P = .036) but not FC (0.10; 95% CI, -0.01 to 0.21; P = .064) or clinical disease activity (0.04; 95% CI, -0.21 to 0.28; P = .768). A composite of IUS and FC showed the greatest association (1.31; 95% CI, 0.43-2.18; P = .003) and accurately predicted histological activity in 88% of cases (P = .007), with sensitivity of 88%, specificity 80%, positive predictive value 95%, and negative predictive value 57%. CONCLUSIONS: Intestinal ultrasound is an accurate noninvasive marker of histological disease activity in UC, the accuracy of which is further enhanced when used in composite with FC. This can reduce the need for colonoscopy in routine care by supporting accurate point-of-care decision-making in patients with UC.

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.

Food-related quality of life in adults with inflammatory bowel disease is associated with restrictive eating behaviour, disease activity and surgery: A prospective multicentre observational study.

BACKGROUND: Measuring food-related quality of life (FRQoL) quantifies the psychosocial impact of eating and drinking. FRQoL and associated factors are not well explored in people with inflammatory bowel disease (IBD), despite IBD being a chronic disease affecting the digestive tract. The present study aimed to characterise and identify any patient or disease-related predictors of FRQoL in individuals with IBD. METHODS: Adults with a formal diagnosis of IBD were recruited to a prospective multicentre cross-sectional study between April 2018 and December 2019. Participants completed questionnaires measuring FRQoL (FRQoL-29), clinical disease activity (Harvey Bradshaw Index and Simple Clinical Colitis Activity Index), restrictive eating behaviour (Nine-Item Avoidant/Restrictive Food Intake Disorder Screen), mental health (Depression Anxiety Stress Scale-21) and other patient and disease-related variables. A multivariable regression was performed to identify factors associated with FRQoL. RESULTS: One hundred and eight participants completed the questionnaires (n = 39, Crohn's disease; n = 69, ulcerative colitis). The mean FRQoL was 79 (95% confidence interval = 75-84) (poor, 0; superior, 145). Poorer FRQoL was observed in those with restrictive eating behaviour associated with fear of a negative consequence from eating (p < 0.0001) and reduced appetite (p < 0.030). Greater FRQoL was observed in those with lower disease activity (p < 0.0001) and previous IBD surgery (p = 0.024). FRQoL was not associated either way by IBD phenotype, duration, or gender. The majority of participants obtained their dietary information from the internet (60%) or gastroenterologist (46%). CONCLUSIONS: FRQoL in people with IBD is poorer in those with restrictive eating behaviours and clinically active disease. Interestingly, it was greater in those with previous IBD surgery. Further research is required to validate these associations and explore longitudinal effects of poor FRQoL on patient outcomes and potential strategies for prevention or management of impaired FRQoL in IBD.

Fecal microbiota transplantation augmented by a sulfide-reducing diet for refractory ulcerative colitis: A case report with functional metagenomic analysis.

Fecal microbiota transplantation (FMT) is effective for induction of remission in ulcerative colitis (UC). Diet has potential to augment the efficacy and durability of FMT by encouraging engraftment of transplanted microorganisms. A trial of FMT combined with a defined diet was undertaken as salvage therapy for a 71-year-old woman with active steroid-refractory extensive UC. A multidimensional sulfide-reducing diet (4-SURE diet) was commenced followed by single-donor FMT administered by colonoscopy and then enemas over 7 days. Dietary adherence, clinical evaluation, and stool samples for metagenomic profiling were undertaken at weeks 0, 4, 8, and 24. Colonoscopy was performed 8 weeks post-FMT. Shotgun metagenomic profiling of the donor fecal suspension was also performed. A rapid clinical response to FMT and 4-SURE diet was observed with normalization of stool frequency (≤2 motions/day) and resolution of rectal bleeding within 2 weeks. Dietary adherence was excellent. Colonoscopy at week 8 revealed no evidence of active colitis (Mayo endoscopic sub-score 0) with histology showing no evidence of acute or chronic lamina propria inflammatory cell infiltrate. Sustained clinical and endoscopic remission out to 24 weeks was observed. Metagenomic sequencing confirmed sustained engraftment of beneficial donor microbiota with increased alpha-diversity and capacity for short-chain fatty acid production, including Faecalibacterium prauznitzii and Eubacterium hallii. This case report supports the rationale of prescribed diet therapy to support engraftment of donor microbiota following FMT for UC. Further large trials with a diet-arm control group are needed to evaluate FMT augmented by a defined diet in UC.

Food avoidance, restrictive eating behaviour and association with quality of life in adults with inflammatory bowel disease: A systematic scoping review.

BACKGROUND: Dietary misconceptions and behaviours may worsen outcomes of inflammatory bowel disease (IBD). This scoping review aims to examine the dietary beliefs and behaviours of individuals with IBD and identify evidence of food avoidance, dietary restriction or disordered eating and any association with quality of life (QoL). METHODOLOGY: A systematic search of CINAL, EMBASE, MEDLINE was conducted. Primary, peer-reviewed studies in English examining dietary beliefs and dietary behaviours or diet and quality of life in adults with inflammatory bowel disease were included. Key dietary terminology was pre-defined. RESULTS: Twenty-nine studies met inclusion criteria. A range of quantitative self-reported questionnaires (16/29), qualitative interviews (1/29) and mixed methods (7/29) were used to measure dietary beliefs and dietary behaviours. A high prevalence of food avoidance (28-89%) and restrictive dietary behaviours (41-93%) were identified. Factors associated with these behaviours included a diagnosis of CD, perceived active disease, female sex, dietary misinformation, and fears of adverse bowel symptoms. Diet and QoL remains largely unexplored in IBD beyond two recent studies demonstrating impairment of food-related quality of life in IBD. CONCLUSION: A high prevalence of self-reported food avoidance and restrictive dietary behaviour exists in people with IBD. The psychosocial impact of IBD-related dietary behaviour is poorly understood. Validated tools with predefined diet terminology and objective markers of disease activity are required to measure dietary behaviour in future prospective studies, using food-related quality of life as an outcome measure.

The Adequacy of Habitual Dietary Fiber Intake in Individuals With Inflammatory Bowel Disease: A Systematic Review.

BACKGROUND: Dietary fiber may influence disease course in individuals with inflammatory bowel disease (IBD), yet there is a paucity of understanding of habitual fiber intakes. OBJECTIVES: To identify studies measuring fiber intakes of individuals with IBD, compare the adequacy of fiber intakes with that of control groups or respective national dietary guidelines, and examine factors associated with fiber consumption. METHODS: Five electronic databases-MEDLINE, CINAHL, SCOPUS, PROQUEST, and COCHRANE LIBRARY-were systematically searched, using search terms inflammatory bowel disease, Crohn's disease, ulcerative colitis, dietary intake, and fiber, until December 2019, with hand searching of reference lists. Primary studies were included if fiber intakes were measured in participants 18 years of age or older, with confirmed IBD, with or without comparison to a control. RESULTS: A total of 2105 publications were identified, and 26 met inclusion criteria. Total fiber intake of 4164 participants with IBD ranged broadly (9.9 ± 7.8 g/day to 21.0 ± 10.5 g/day). Most (18/26) used cross-sectional study design, with a large degree of heterogeneity in tools measuring fiber intake. Sixty-six percent of studies comparing participants with IBD with control groups found that participants with IBD consumed significantly less fiber than control subjects. Four studies reported that less than 10% to 21% of IBD participants met their national fiber recommendations. Data conflicted regarding an association between disease type, disease activity, or rate of relapse and fiber intake. CONCLUSIONS: Individuals with IBD consume less fiber than healthy populations. Fiber intakes are inadequate compared with respective national fiber guidelines. Interpretation of factors associated with fiber intakes were limited by data quality and conflicting results. Future research is required into factors associated with fiber intake and whether increasing fiber intakes can influence disease course and behavior.